Hematologic/Blood Cancers – NCI-07-C-0195
Dr. Michael R. Bishop
Principal Investigator
NCI’s Center for Cancer Research (CCR) is currently conducting the following trial for patients with non-Hodgkin's lymphoma and chronic lymphocytic leukemia. Click on the trial below for additional details, including a summary of primary eligibility, study outline, and information on how to contact Dr. Bishop and his staff directly.
You may also call the Clinical Trials Referral Office at 1-888-NCI-1937 (1-888-624-1937) to inquire about referring a patient to this trial.
Induction Chemotherapy:
Patients receive 1 of 2 induction chemotherapy regimens (EPOCH-F/R vs FLAG) based on diagnosis.
- EPOCH-F/R (for patients with Hodgkin lymphoma, non-Hodgkin lymphoma, chronic lymphocytic leukemia, prolymphocytic leukemia, or multiple myeloma):
- Patients receive fludarabine phosphate IV over 30 minutes once daily, etoposide IV continuously, doxorubicin hydrochloride IV continuously, and vincristine IV continuously on Days 1–4
- Patients receive cyclophosphamide IV over 30 minutes on Day 5; and oral prednisone on Days 1–5
- Patients with CD20+ disease also receive rituximab IV on Day 1
- All patients receive filgrastim (G-CSF) subcutaneously (SC) beginning on Day 6 and continuing until blood counts recover
- Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity
- FLAG (for patients with acute myeloid leukemia, acute lymphocytic leukemia, myelodysplastic syndromes, chronic myelogenous leukemia, myeloproliferative disorders, or chronic myelomonocytic leukemia):
- Patients receive fludarabine phosphate IV over 30 minutes and cytarabine IV over 4 hours on Days 1–5
- Patients also receive G-CSF SC beginning on Day 0 and continuing until blood counts recover
- Treatment repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity
- Patients with responsive or stable disease after receiving EPOCH-F/R and patients who achieve remission after FLAG proceed to allogeneic hematopoietic stem cell transplantation
Preparative regimen and allogeneic hematopoietic stem cell transplantation (HSCT):
- Patients receive fludarabine phosphate IV over 30 minutes and cyclophosphamide IV over 2 hours on Days -6 to -3
- Patients undergo G-CSF-mobilized allogeneic HSCT on Day 0
- Patients also receive G-CSF SC beginning on Day 0 and continuing until blood counts recover
Graft-versus-host disease (GVHD) prophylaxis:
Patients are randomized at study enrollment to receive 1 of 2 GVHD prophylaxis regimens.
Arm I (TMS)
- Patients receive tacrolimus IV continuously or orally and oral sirolimus on Days -3 to 63, followed by a taper if GVHD does not develop
- Patients also receive methotrexate IV over 15 minutes on Days 1, 3, 6, and 11
Arm II (CA)
- Patients receive alemtuzumab IV over 8 hours on Days -8 to -4
- Patients also receive cyclosporine IV over 2 hours or orally every 12 hours on Days -1 to 100, followed by a taper if GVHD does not develop
- Patients with persistent or progressive malignancy post-HSCT or mixed chimerism that does not improve after tapering or discontinuing immune suppression may receive donor lymphocyte infusions (DLIs)
- DLI may be administered alone or after chemotherapy every 4 weeks provided GVHD is not present
- Blood samples are obtained at baseline and then periodically before and after HSCT
- Punch biopsies of skin and buccal mucosa and whole saliva samples are collected at Day 63 and at 6 months (or at the development of GVHD) post-transplant and examined by immunofluorescence, confocal microscopy, gene expression profiles, and protein-based assays
- After completion of study therapy, patients are followed periodically for 2 years
Why is this trial important?
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.
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