Clinical Trials in the Spotlight

A Clinical Research Study in Patients With Leukemias, Lymphomas, and Pre-malignant Blood Disorders using Matched Unrelated Cord Blood Transplant.

Mon, 19 Oct 2009 12:01:14 -0400

Pilot Trial of Targeted Immune-Depleting Chemotherapy and Reduced-Intensity Matched Unrelated Double Cord Blood Transplant for the Treatment of Leukemias, Lymphomas, and Pre-Malignant Blood Disorders

Because only 25–30% of patients have an HLA-identical sibling donor, and many patients do not have an adequately HLA-matched unrelated donor, especially racial and ethnic minorities, the transplantation of umbilical cord blood (UCB) represents the most recent strategy to expand the potential donor pool. Umbilical cord blood transplantation permits a higher degree of HLA disparity while demonstrating a reduction in the incidence of graft versus host disease (GVHD) compared with unrelated donor and hapoidentical transplant modalities. The major limitations of umbilical cord blood transplantation (UCBT) in adults are graft rejection and delayed engraftment leading to increased infection-related morbidity and treatment-related mortality (TRM). To increase engraftment rates while enhancing graft-versus- tumor effect, previous studies within our institution have employed the strategy of targeted immune depletion (TID). The TID approach attempts to compensate for variability in host immune status and facilitate engraftment by using repetitive cycles of disease-specific conventional-dose chemotherapy to provide both tumor control and lymphocyte depletion prior to transplant. Our aim in the current protocol is to extend the strategy of TID to reduced-intensity UCBT, with the goal of more rapid engraftment, leading to decreased TRM and increased overall survival. Our intention is to investigate this approach in the setting of double cord blood transplant in adults in a pilot manner.

A Clinical Research Study in Patients With Leukemias, Lymphomas, and Pre-malignant Blood Disorders using Unrelated Donor Stem Cell Transplant.

Mon, 19 Oct 2009 11:58:57 -0400

Pilot Trial of Targeted Immune-Depleting Chemotherapy and Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation Using 8/8 and 7/8 HLA-Matched Unrelated Donors and Utilizing Two Graft-versus-Host Disease Prophylaxis Regimens for the Treatment of Leukemias, Lymphomas, and Pre-malignant Blood Disorders

This trial utilizes a strategy of targeted immune-depleting chemotherapy prior to reduced-intensity allogeneic hematopoietic stem cell transplant (HSCT) from unrelated donors. This strategy permits an individualized approach, as the amount of chemotherapy that is administered prior to the transplant is based upon the individual patient's immune status to insure that there is adequate immune suppression to permit the rapid and complete engraftment of donor stem cells. A second important aspect of this trial is to study reconstitution of the immune system following transplant. The study employs two different regimens to prevent graft-versus-host disease (GVHD). Both regimens have been successfully used to prevent GVHD, but they work by different mechanism and have different effects upon the immune system. The specific regimen that a patient receives is randomly assigned. Our study of immune reconstitution is intended to help in the development of therapies to further improve on the results of these two regimens.

A Clinical Research Study in Patients With Metastatic Melanoma.

Mon, 19 Oct 2009 11:57:20 -0400

Phase II Study in Patients With Metastatic Melanoma Using a Non-Myeloablative Lymphocyte Depleting Regimen of Chemotherapy Followed by Infusion of Tumor Reactive Peripheral Blood Lymphocytes (PBL) and High or Low Dose Aldesleukin

Over the past decade, the incidence of melanoma in the United States has shown a dramatic increase. Melanoma is highly curable when identified and treated at in its earliest stage. However, there are very few therapeutic options when metastases develop. Immune-based therapies have shown recent promise. In pilot clinical trials, the adoptive transfer of autologous tumor-specific lymphocytes has demonstrated the ability to induce objective and durable clinical responses.

A Clinical Research Study in Patients With Advanced HIV-Related or HIV-Unrelated (Classic) Kaposi Sarcoma.

Fri, 2 Oct 2009 09:43:28 -0400

Pilot Study of Liposomal Doxorubicin Combined With Bevacizumab Followed by Bevacizumab Monotherapy in Adults With Advanced Kaposi's Sarcoma

Kaposi sarcoma (KS) is a rare tumor with increased incidence in several special populations: patients with HIV, transplant patients, and elderly patients infected with the virus, Kaposi sarcoma-associated herpesvirus. The current standard of care in advanced KS includes the use of liposomal doxorubicin (or liposomal daunorubicin). In a subset of patients, treatment requires long-term use of liposomal anthracyclines beyond the maximum recommended cumulative dose. Furthermore, while liposomal doxorubicin is generally effective, patients with advanced disease, especially when there is pulmonary involvement, may have poor outcome with liposomal doxorubicin alone. This trial builds on the previous studies in KS performed by the HIV and AIDS Malignancy branch by combining an anti-angiogenic agent, bevacizumab, with liposomal doxorubicin, followed by bevacizumab alone. By only using liposomal doxorubicin for a limited time, this regimen would be anthracycline-sparing as compared to treatment with just liposomal doxorubicin. We are testing the hypothesis that this regimen will be will tolerated and may be more active in patients with advanced KS than liposomal doxorubicin alone.

A Clinical Research Study in HIV Infected HLA-A2 Patients.

Fri, 2 Oct 2009 09:37:13 -0400

A Pilot Study to Investigate the Safety and Immunogenicity of a Peptide Vaccine for HIV Infected HLA-A2 Individuals Designed to Impede Development of Antiretroviral Resistance

This study will test a novel approach to treating HIV that combines a peptide experimental therapeutic vaccine with antiretroviral therapy. The vaccine is designed to enhance immunity against an HIV mutation that caused resistance to certain drugs (such as lamivudine) and it is possible that this approach may help delay the development of resistance to certain antiretroviral drugs.

A Clinical Research Study in Patients With HIV-Related or HIV-Unrelated (Classic) Kaposi Sarcoma.

Fri, 2 Oct 2009 09:34:39 -0400

Phase I and Pharmacokinetic Study of BAY 43-9006 (Sorafenib) in Patients With Kaposi's Sarcoma

At the present time, systemic chemotherapy for Kaposi's sarcoma usually involves cytotoxic chemotherapy drugs that have short-term and cumulative toxicities. As a result, novel targeted therapies are urgently needed. This trial is exploring a novel targeted therapy that blocks several specific pathways believed to be important in the formation and growth of Kaposi's sarcoma. BAY 43-9006 (also called sorafenib) blocks both mutant and wild-type c-Raf kinase, which is important in the formation of many tumors. This drug was recently approved for patients with advanced kidney cancer, and there is thus substantial human experience with the agent. BAY 43-9006 blocks several receptors that appear to be particularly important in Kaposi's sarcoma, including a special form of the receptor for vascular endothelial growth factor (VEGF-R3).

A Clinical Research Study in Patients With AIDS-Related Primary Central Nervous System Lymphoma.

Fri, 2 Oct 2009 09:31:05 -0400

AIDS-Related Primary Central Nervous System Lymphoma: A Phase II Pilot Study of High-Dose Intravenous Methotrexate With Rituximab Leucovorin Rescue and Highly Active Antiretroviral Therapy

AIDS-related primary brain lymphoma is a serious and life threatening complication of HIV infection. Few individuals with this cancer survive for one year. Radiation therapy to the brain is the treatment commonly administered. Radiation therapy can make the lymphoma go away. However, many patients have recurrence of the lymphoma after radiation therapy, or develop other AIDS complications that limit survival. With the availability of highly active antiretroviral therapy, many individuals with AIDS-related primary brain lymphoma may be able to control the HIV infection long-term and go on to good health if the lymphoma can be cured. Many non-HIV-infected people treated with radiation therapy for brain lymphoma survive several years, but have severe brain problems related to the radiation treatment. Therefore, in non-HIV-infected people, chemotherapy has become the standard of care for treating this cancer. Survival with a healthy brain in such people is improved with this strategy. This clinical trial will assess whether chemotherapy will lead to several years or longer survival without brain problems in people with AIDS-related primary brain lymphoma.

A Clinical Research Study in Patients With KSHV-Associated Multicentric Castleman's Disease.

Fri, 2 Oct 2009 09:27:58 -0400

Targeted Oncolytic Virotherapy and Natural History Study of KSHV-Associated Multicentric Castleman's Disease With Laboratory and Clinical Correlates of Disease Activity

This trial is important because KSHV-associated multicentric Castleman's disease is a poorly understood condition, and there is no standard medical treatment for the disease. This trial is designed to gather information about the disease and to develop new treatment strategies for the disease. The interventions being studied in this trial may have application to other rare diseases if they appear to be effective in this trial.

A Clinical Research Study in Patients With Unresectable Malignant Epithelial Pleural Mesothelioma.

Mon, 3 Aug 2009 11:19:17 -0400

An Open-Label Clinical Trial of MORAb-009 in Combination With Pemetrexed and Cisplatin in Subjects With Mesothelioma

The goal of this trial is to determine if adding the anti-mesothelin monoclonal antibody MORAb-009 to the standard chemotherapy drugs used to treat mesothelioma will improve the prognosis of patients with mesothelioma.

A Clinical Research Study in Patients With Unresectable Malignant Epithelial Pleural Mesothelioma.

Mon, 3 Aug 2009 11:17:01 -0400

Phase I, Single Center, Dose-Escalation Study of SS1(dsFv)-PE38 Administered Concurrently With Pemetrexed and Cisplatin in Subjects With Unresectable Malignant Epithelial Pleural Mesothelioma

Malignant mesothelioma is an aggressive disease. Chemotherapy with pemetrexed plus cisplatin is the standard first-line therapy for malignant mesothelioma for patients with unresectable disease, but the treatment results in a median overall survival of only 12.1 months. In this trial, we combine SS1P, an immunotoxin, with standard first-line chemotherapy. Hopefully, the combination of SS1P with pemetrexed plus cisplatin can result in improved outcomes for patients with mesothelioma.

A Clinical Research Study in Patients With Thymoma or Thymic Carcinoma.

Mon, 3 Aug 2009 11:14:14 -0400

Multicenter Phase II Study of Belinostat (PXD101) in Previously Chemotherapy Treated Thymoma and Thymic Carcinoma

Thymic malignancies are rare tumors of the anterior mediastinum. Platinum-based chemotherapy is used for first-line treatment of advanced disease. There is no established alternative or second-line therapy for patients with refractory or recurrent disease. This study will assess the response rate of tumors to belinostat, a histone deacetylase inhibitor with antineoplastic activity, in patients who have previously been treated with platinum-based chemotherapy and whose tumors cannot be removed by surgery.

A Clinical Research Study in Patients With Thoracic Malignancies.

Mon, 3 Aug 2009 11:12:43 -0400

Prospective Evaluation of Epigenetic Alterations in Patients With Thoracic Malignancies

This protocol is designed to facilitate screening of patients for investigational protocols in the Thoracic Oncology Section, Surgery Branch, NCI, and in doing so, obtain tissue samples to enable evaluation of epigenetic events in primary and metastatic thoracic malignancies, as an extension of ongoing laboratory research in the Thoracic Oncology laboratory.

A Clinical Research Study in Patients With Advanced Lung or Esophageal Cancer, Malignant Pleural Mesothelioma, or Pleural Metastases.

Mon, 3 Aug 2009 11:06:02 -0400

Phase I Study of Sequential Depsipeptide/Flavopiridol Infusion in Patients With Malignancies Involving Lungs, Esophagus, or Pleura

This trial is being done because previous animal and laboratory studies show that these medicines have reduced the growth of different types of tumor cells, and the initial studies in humans found that these medicines can be given safely. This trial is to test the safety of two experimental medications given together as well as testing the effects of this drug combination on the patients' cancer. Based on our laboratory studies, we think if we give these two drugs together, they will work better at shrinking cancers than either one given alone.

A Clinical Research Study in Patients With Lung or Esophageal Cancer, Malignant Pleural Mesothelioma, or Lung or Pleural Metastases.

Mon, 3 Aug 2009 11:03:57 -0400

Phase I Study of Gene Induction Mediated by Sequential Decitabine/Depsipeptide Infusion With or Without Concurrent Celecoxib in Subjects With Pulmonary and Pleural Malignancies

This trial uses two experimental medicines that have not been used together before. We are testing the effects these two medicines have on the patients' cancer. We are doing this study because previous animal and laboratory studies show that these medicines have reduced the size of different kinds of tumors, and the initial studies in humans found that these medicines can be given safely. We are looking at specific changes in the tumors and in the blood that indicate whether or not the cancer is responding to therapy.

A Clinical Research Study in Patients With Colorectal, Lung, Head and Neck, Hepatocellular, Renal cell, Pheochromocytoma, and Thyroid Tumors.

Mon, 3 Aug 2009 10:59:36 -0400

A Broad Multi-Histology Phase II Study of the Multi-Kinase Inhibitor R935788 (Fostamatinib Disodium) in Advanced Colorectal, Non-Small Cell Lung, Head and Neck, Hepatocellular and Renal Cell Carcinomas, and Pheochromocytoma and Thyroid Tumors

Protein kinases play important roles in regulating most cellular functions; deregulated protein kinase activity is a frequent cause of cancer. R935788 is a kinase inhibitor with activity against multiple cancer types in experimental models. Based on the promising activity observed in these model systems, R935788 is being evaluated as a treatment for multiple cancer types.

A Clinical Research Study in Patients With Malignant Peripheral Nerve Sheath Tumors.

Mon, 29 Jun 2009 13:58:03 -0400

Phase II Trial of Chemotherapy in Sporadic and Neurofibromatosis Type 1 Associated High Grade Unresectable Malignant Peripheral Nerve Sheath Tumors

Malignant peripheral nerve sheath tumors (MPNSTs) account for 10% of all soft tissue sarcomas, and 50% of MPNSTs arise in patients with neurofibromatosis type 1 (NF1). Surgery is the only curative treatment option. The prognosis of incompletely resected or metastatic MPNSTs is poor, and may be worse for NF1-associated MPNSTs. The response rate of MPNSTs to standard chemotherapy agents used in the treatment of pediatric and adult soft tissue sarcomas is unknown. The goal of this multicenter phase II clinical trial is to compare the clinical response rate of high-grade, unresectable, or metastatic sporadic vs NF1-associated MPNSTs after chemotherapy with four cycles of standard sarcoma chemotherapy. As the outcome for NF1-associated MPNST has been reported to be worse compared to sporadic tumors, this trial will evaluate outcome in the two groups treated with identical therapy in an attempt to determine if patients with NF1-associated MPNSTs have a worse prognosis.

A Clinical Research Study in Patients With Adult T-Cell Leukemia.

Wed, 17 Jun 2009 13:28:24 -0400

Phase II Trial of LMB-2, Fludarabine, and Cyclophosphamide for Adult T-Cell Leukemia

Patients with adult T-cell leukemia (ATL) generally have tumor burden that increases quickly after chemotherapy. Although some treatments work temporarily, there are no effective treatments that are considered standard. The ATL cells display very high levels of CD25 and are rapidly killed by LMB-2. The recombinant anti-CD25 immunotoxin LMB-2 contains an antibody fragment binding to CD25 and a toxin that kills once it gets inside the cell. LMB-2 is highly effective in killing ATL cells in patients, but success is limited by patients making antibodies that neutralize LMB-2, and also by ATL cells growing between the 3-week cycles of treatment. To solve both problems, chemotherapy consisting of fludarabine and cyclophosphamide (FC) will be given prior to LMB-2. FC chemotherapy will be given both to prevent neutralizing antibodies and to reduce the ATL cell number before LMB-2 so that tumors do not grow back between cycles of LMB-2.

A Clinical Research Study in Patients With Hairy Cell Leukemia.

Wed, 17 Jun 2009 13:26:30 -0400

Randomized Trial of Cladribine (CdA) With Simultaneous or Delayed Rituximab to Eliminate Hairy Cell Leukemia Minimal Residual Disease

Cladribine is highly effective for hairy cell leukemia (HCL), with most patients remaining in complete remission over 8 years, but it leaves patients with minimal residual disease (MRD) that prevents cure. Patients not dying of other causes often relapse, grow refractory to cladribine, and die of infections. To prevent relapse by eradicating the HCL-MRD, the anti-CD20 antibody rituximab will be given along with cladribine. It is possible that the rituximab will work best if it is first used at least 6 months after cladribine when MRD is first detectable in the blood because it can take up to 6 months for the HCL tumor deposits to reach a minimum size. It is also possible that rituximab will work best if started with the first dose of cladribine because even though tumor is largest at that time, the two drugs may work best together. Half the patients will receive each approach.

A Clinical Research Study in Patients With Hairy Cell Leukemia.

Wed, 17 Jun 2009 13:23:29 -0400

A Phase I, Multicenter, Dose-Escalation Study of CAT-8015 in Patients With Relapsed or Refractory Hairy Cell Leukemia

Patients who have been treated many times for hairy cell leukemia (HCL) often have poor responses to standard treatment, have cumulative toxicity from chemotherapy, and can die of refractory HCL, usually from infections. HCL cells that are resistant to chemotherapy display high levels of CD22, making them good targets for HA22, a recombinant immunotoxin that binds to CD22 using an antibody fragment, goes inside the cell and has a toxin fragment that kills the cell. HA22 is an improved version of BL22, and it is reported to achieve complete remissions in a high percentage of HCL patients resistant to chemotherapy.

A Clinical Research Study in Patients With Cutaneous T-Cell Lymphoma.

Wed, 17 Jun 2009 13:21:05 -0400

A Phase II Clinical Trial of Anti-Tac(Fv)-PE38 (LMB-2) Immunotoxin for Treatment of CD25 Positive Cutaneous T-Cell Lymphomas

Patients with cutaneous T-cell lymphoma, particularly in advanced stages, need additional options for therapy. The malignant cells often display the marker CD25, which makes them potential targets for the recombinant immunotoxin LMB-2.

A Clinical Research Study in Patients With Progressive or Recurrent Metastatic Melanoma After High-Dose Aldesleukin.

Mon, 1 Jun 2009 10:46:32 -0400

Phase II Study of Metastatic Melanoma Using a Chemoradiation Lymphodepleting Conditioning Regimen Followed by Infusion of Anti-Mart-1 and Anti-gp100 TCR-Gene Engineered Lymphocytes and Peptide Vaccines

Gp100 and MART-1 are melanoma proteins that are usually expressed in melanoma tumors from patients. Because standard therapies to treat melanoma are rarely curative, alternative approaches to the treatment of patients with gp100-expressing and MART-1-expressing melanomas whose tumors have not responded to standard available therapies are needed. The type of experimental therapy proposed in this protocol uses genetically modified autologous cells and a vaccine, both of which activate the immune system to target melanoma that expresses gp100 and MART-1. Similar approaches have been used at the Surgery Branch for several years to treat patients with malignant melanoma.

A Clinical Research Study in Patients With Recurrent or Progressive Cancer That Expresses CEA.

Mon, 1 Jun 2009 10:44:29 -0400

Phase II Study of Metastatic Cancer That Expresses Carcinoembryonic Antigen (CEA) Using Lymphodepleting Conditioning Followed by Infusion of Anti-CEA TCR-Gene Engineered Lymphocytes

Carcinoembryonic antigen (CEA) is a protein that is highly overexpressed in malignant colorectal cancer, breast cancer, pancreatic cancer, lung cancer, and other adenocarcinomas. High circulating CEA serum levels are also present in cancer patients, and increased CEA levels have been associated with poor prognosis. Therefore, alternative approaches to the treatment of patients with CEA-expressing tumors whose tumors have not responded to standard available therapies are needed. The type of experimental therapy proposed in this protocol uses genetically modified cells and this approach has been used at the Surgery Branch for several years to treat patients with malignant melanoma. It is hoped that patients with tumors that express the CEA protein can benefit from this.

A Clinical Research Study in Patients With Recurrent or Progressive Cancer That Expresses NY-ESO-1.

Mon, 1 Jun 2009 10:33:56 -0400

Phase II Study of Metastatic Cancer That Expresses NY-ESO-1 Using Lymphodepleting Conditioning Followed by Infusion of Anti-NY ESO-1 TCR-Gene Engineered Lymphocytes

ESO-1 is a protein that is expressed in approximately one-third of melanoma, breast, prostate, lung, ovarian, thyroid, and bladder cancers, as well as sarcomas. ESO-1 is mostly found in cancer cells, making it a good target for novel cancer therapies. Therefore, we developed an approach to the treatment of patients with ESO-1-expressing tumors by targeting the ESO-1 protein by activating the patients’ immune system. The type of experimental therapy proposed in this protocol uses genetically modified cells and this approach has been used at the Surgery Branch for several years to treat patients with malignant melanoma, testing other melanoma proteins. It is hoped that patients with all tumors that express the ESO-1 protein can benefit from this approach.

A Clinical Research Study in Patients With Progressive or Recurrent Metastatic Melanoma After High-Dose Aldesleukin.

Mon, 1 Jun 2009 10:27:25 -0400

Phase II Study of Metastatic Melanoma Using Lymphodepleting Conditioning Followed by Infusion of Anti-gp100:154-162 TCR-Gene Engineered Lymphocytes and ALVAC Virus Immunization

Gp100 is a melanoma protein that is usually expressed in melanoma tumors from patients. Because standard therapies to treat melanoma are rarely curative, alternative approaches to the treatment of patients with gp100-expressing melanomas whose tumors have not responded to standard available therapies are needed. The type of experimental therapy proposed in this protocol uses genetically modified autologous cells and a new vaccine both of which activate the immune system to target melanoma that expresses gp100. Similar approaches have been used at the Surgery Branch for several years to treat patients with malignant melanoma.

A Clinical Research Study in Patients With Stage IIIA Non-Small Cell Lung Cancer.

Thu, 14 May 2009 09:10:58 -0400

Phase II Study of Neoadjuvant Gemcitabine, Cisplatin, and Bevacizumab in Stage IIIA (N2) Non-Squamous Cell Non-Small Cell Lung Cancer

This trial is important because it will evaluate the role of chemotherapy before surgery for certain cases of lung cancer. By administering chemotherapy prior to surgery, we hope to decrease the size of the tumor in an effort to allow for easier and more complete resection of the tumor.

A Clinical Research Study in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC).

Thu, 14 May 2009 09:18:11 -0400

A Phase III, Randomized, Double-Blind, Placebo-Controlled Study of Oral Talactoferrin in Addition to Best Supportive Care in Adults With Non-Small Cell Lung Cancer (NSCLC) Who Have Failed Two or More Prior Treatment Regimens

Currently, we are limited in the treatment options for patients with advanced non-small cell lung cancer (NSCLC). The use of standard chemotherapy using a platinum agent in addition to another approved chemotherapy agent has resulted in only small improvements in the overall survival of patients with lung cancer. Recurrent and progressive disease after initial treatment has even fewer chemotherapy options. Erlotinib is currently the only oral agent approved in the United States for the treatment of advanced NSCLC. There is great need to further develop and examine new agents for the treatment of advanced NSCLC. This trial will determine the safety and tolerability of oral talactoferrin in the treatment of recurrent or progressive NSCLC.

A Clinical Research Study in Patients Undergoing Surgical Resection of Non-Small Cell Lung Cancer.

Thu, 14 May 2009 09:23:05 -0400

Pilot Trial of Pioglitazone in Patients Undergoing Surgical Resection of Non-Small Cell Lung Cancer

Pioglitazone is currently used for the treatment of diabetes, but laboratory evidence suggests that it may be able to prevent certain types of cancer. This pilot trial will examine the effect of pioglitazone on normal, pre-cancerous, and cancer cells in the lung, allowing researchers to determine whether it is effective enough so that it should be studied for cancer prevention or treatment in subsequent larger studies.

A Clinical Research Study in Patients With Advanced Non-Small Cell Lung Cancer (NSCLC) Following Front-Line Chemotherapy.

Thu, 14 May 2009 09:25:32 -0400

Registration Phase III Study of Lucanix^TM (Belagenpumatucel-L) in Advanced Non-Small Cell Lung Cancer: An International Multicenter, Randomized, Double-Blinded, Placebo-Controlled Study of Lucanix^TM Maintenance Therapy for Stages III/IV NSCLC Subjects Who Have Responded to or Have Stable Disease Following One Regimen of Front-Line, Platinum-Based Combination Chemotherapy

There are currently no approved treatments after patients have received initial chemotherapy for advanced lung cancer. This study is a placebo-controlled trial to determine if using the vaccine Lucanix^TM (Belagenpumatucel-L) will prolong survival in advanced NSCLC immediately after use of standard platinum-based chemotherapy in patients who had a response or had stable disease as result of the treatment.

A Clinical Research Study in Patients With Relapsed Non-Small Cell Lung Cancer.

Thu, 14 May 2009 09:40:37 -0400

Phase II Study of BAY 43-9006 (Sorafenib) With Evaluation of Ras Signal Pathway in Patients With Relapsed Non-Small Cell Lung Cancer

Currently, we are limited in the treatment options for patients with advanced non-small cell lung cancer (NSCLC). The use of standard chemotherapy using a platinum agent in addition to another approved chemotherapy agent has resulted in only small improvements in the overall survival of patients with lung cancer. Recurrent and progressive disease after initial treatment has even fewer chemotherapy options. Erlotinib is currently the only oral agent approved in the United States for the treatment of advanced NSCLC. There is great need to further develop and examine new agents for the treatment of advanced NSCLC. This trial will determine the safety and efficacy of BAY 43-9006 (sorafenib) in the treatment of recurrent or progressive NSCLC.

A Clinical Research Study in Patients With Relapsed or Refractory Lymphoid Malignancies.

Thu, 14 May 2009 09:50:41 -0400

A Phase I/IIa Study Evaluating the Safety, Pharmacokinetics and Efficacy of ABT-263 in Subjects With Relapsed or Refractory Lymphoid Malignancies

This study aims to determine the highest dose of ABT-263 that can safely be given to patients with lymphoma while evaluating the safety and effectiveness of ABT-263 in treating patients with lymphoma that has recurred (come back) or is refractory (did not respond to prior treatment). In addition, we hope to determine how the body absorbs and handles ABT-263. Finally, we hope to find biomarkers (substances in the blood or tissue that may indicate the effects or progress of the disease and activity of ABT-263).

A Clinical Research Study in Patients With Lymphomatoid Granulomatosis.

Thu, 14 May 2009 09:55:06 -0400

Treatment and Natural History Study of Lymphomatoid Granulomatosis

Lymphomatoid granulomatosis (LYG) is an extremely rare lymphoproliferative disorder associated with Epstein-Barr Virus (EBV) infection. It is frequently encountered in patients who have a weakened or deficient immune system. It can involve several different organs that include the lungs, skin, kidneys, and central nervous system. LYG is divided into 3 different grades with grades 1 and 2 being under the control of the immune system and grade 3 being immune independent and behaving like an aggressive lymphoma. With conventional therapy, the prognosis for LYG is very poor. Our protocol is investigating the use of Interferon in patients with grades I and II LYG and DA-EPOCH-R in patients with grade III disease. So far, our results have been very promising. We are also investigating the immune system abnormalities of this disease in an attempt to understand what causes it and why it happens.

A Clinical Research Study in Patients With HTLV-1-Associated Adult T-cell Leukemia/Lymphoma.

Thu, 14 May 2009 09:58:07 -0400

Phase II Study of the Efficacy and Toxicity of Ontak® (Denileukin Diftitox) in the Therapy of Adult T-Cell Leukemia

ATL is an aggressive T-cell lymphoproliferative disorder characterized by the presence of malignant CD4/CD25-expressing T cells in the peripheral blood, lymph nodes and other tissues. The various combination chemotherapies so far developed have not increased significantly the survival of patients with ATL. New approaches to treatment are needed and CD25 presents an attractive target for therapy. This fusion molecule delivers diphtheria toxin to the cancer cells because of their expression of CD25 which the interleukin-2 molecule binds to and is internalized.

A Clinical Research Study in Patients With Relapsed or Refractory Lymphoma.

Thu, 14 May 2009 10:04:59 -0400

A Pilot Study of MDX-CTLA-4 in Lymphoma

Monoclonal antibodies have become an important addition to the management of patients with cancer. MDX-CTLA-4 is a human antibody that binds to a protein called CTLA-4. The antibody interrupts signals by CTLA-4 and may act to inhibit the normal pathways that regulate and control the expansion of T cells. Although this process has been associated with tumor responses in patients with lymphoma and other cancers, it is not clear why some people develop an autoimmune disorder while others do not. We are trying to find out if the development of autoimmunity has a direct relationship with tumor response and if there are features in tumors that predict a greater chance for response to treatment.

A Clinical Research Study in Patients With Untreated Lymphoma.

Thu, 14 May 2009 09:52:03 -0400

Phase III Randomized Study of R-CHOP Versus Dose-Adjusted EPOCH-R With Molecular Profiling in Untreated De Novo Diffuse Large B-Cell Lymphomas.

This study aims to compare two different treatment approaches for diffuse large B-cell lymphoma: R-CHOP, the standard therapy, versus dose-adjusted EPOCH-R, a regimen developed from studies on drug schedule and resistance and pharmacokinetics that had promising results in phase 2 studies. This study also will assess multiple biological factors, employing molecular profiling, proteomics, and genomics with an aim toward understanding the biological basis of response and tumor biology.

A Clinical Research Study in Patients With T-Cell Large Granular Lymphocytic Leukemia.

Thu, 14 May 2009 10:06:47 -0400

A Phase I Open-Label Single-Dose Study of Humanized MiK-Beta-1 Monoclonal Antibody Directed Toward the IL-2R/IL-15R{beta} Subunit (CD122) in T-Cell Large Granular Lymphocytic Leukemia

This the first clinical trial studying the activity and effects of a humanized monoclonal antibody (Mik-beta-1) targeting the beta chain shared by the interleukin-2 (IL-2) and interleukin-15 (IL-15) receptors on the surface of lymphocytes. The binding of IL-15 to its receptor is thought to stimulate the growth of T-cell large granular lymphocyte leukemia (T-LGL). Blocking of IL-15 from binding to its receptor may slow or stop the growth of T-LGL cells, decrease the number of leukemic cells in the circulation and improve T-LGL-associated hemocytopenias.

A Clinical Research Study in Patients With HTLV-1 Associated Adult T-Cell Leukemia.

Thu, 14 May 2009 10:08:49 -0400

Phase I/II Study of the Efficacy and Toxicity of Humanized Anti-Tac (Zenapax®) in the Therapy of Tac-Expressing Adult T-Cell Leukemia.
HTLV-1-associated adult T-cell leukemia/lymphoma (ATL) is an aggressive lymphoproliferative disorder characterized by rapidly rising white blood cell counts, hypercalcemia, skin involvement, hepatosplenomegaly and lytic bone lesions. It is often poorly responsive to standard chemotherapy and patient survival is limited. This clinical trial is studying daclizumab (Zenapax®), a humanized monoclonal antibody targeting the interleukin-2 (IL-2) receptor (CD25) that is over expressed on the surface of ATL cells. Daclizumab blocks the binding of IL-2 to the receptor. This trial is focusing on patients with smoldering and chronic stage ATL where the interaction of IL-2 with its receptor (CD25) is believed to play a role in stimulating tumor cell proliferation and progression of ATL. Phase I demonstrated that high saturating doses of daclizumab could be safely administered to ATL patients. Binding of the CD25 receptor by daclizumab and blocking of IL-2 binding may slow the progression of ATL.

A Clinical Research Study in Patients With Advanced Hematologic Diseases.

Thu, 14 May 2009 10:10:24 -0400

A Clinical Research Study in Patients With B-Cell Lymphoid Malignancies After Prior Allogeneic HSCT.

Thu, 14 May 2009 10:28:45 -0400

Adoptive Cell Therapy for B-Cell Malignancies After Allogeneic Hematopoietic Stem Cell Transplantation With Costimulated, Tumor-Derived Lymphocytes

The prognosis for patients with B-cell lymphoid malignancies (BCL) with relapse or refractory disease after allogeneic hematopoietic stem cell transplantation (alloHSCT) is poor. Effective therapy for patients who fail withdrawal of immune suppression and administration of donor lymphocyte infusions (DLI) has not been identified. Further, in the setting of recurrent or refractory BCL, the immunologic graft-versus-tumor (GVT) effect generated by unmanipulated donor lymphocytes is often not durable and can be accompanied by graft-versus-host disease (GVHD). Generation of donor lymphocytes that mediate more potent and specific GVT effects is a major goal of transplantation research. We have hypothesized that lymphocytes found in tumor after alloHSCT are of donor origin, and because they are tumor-derived, they may be tumor-specific in their homing and antigen specificity characteristics. Further, activation and expansion of these cells through CD3/CD28 costimulation may yield a more effective form of cell therapy after alloHSCT, with enhanced GVT effects and less GVHD.