Post Transplant Donor Lymphocyte Infusion

• Status: Terminated
• Trial end date: 2018-12-24
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to test the hypothesis that a pre-infusion preparative regimen of cyclophosphamide and fludarabine will improve the effectiveness of DLI in patients with blood cancers.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Masonic Cancer Center, University of Minnesota
• Treatments: Cyclophosphamide; Fludarabine

Criteria

Inclusion Criteria:

• Patients (age > or = 1 years) with a diagnosis of relapse after related or unrelated allogeneic stem cell transplantation for a hematological malignancy.

• For CML, relapse will be defined as any cytogenetic evidence of a Philadelphia chromosome or persistence of BCR/ABL rearrangements by molecular testing on at least two measurements over a 6 month interval. If cytogenetics are normal and there is PCR evidence of a BCR/ABL fusion, patients will be eligible if they have evidence of a quantitative increase in CML measured either by quantitative PCR or by fluorescent in situ hybridization (FISH).

• For non-CML, relapse will be defined based on disease specific morphologic criteria from a bone marrow biopsy and aspirate or recurrence of disease specific cytogenetics. For disease specific definition of relapse, see appendix 3. Relapse can be determined morphologically with less than 5 percent blasts if definitive relapse can be determined. Equivocal results for relapse should result in a repeated test after an appropriate time interval (suggested 1 month) to determine eligibility.

Post-transplant lymphoproliferative diseases (often referred to as EBV-associated lymphomas) are NOT eligible for this protocol.

• For Chronic Phase CML patients only

• - must have failed (no response in 3 months or incomplete response at 6 months) or refused treatment with Gleevec

• - if no prior DLI, CML patients will first have DLI- if relapse occurs after DLI, DLI with chemotherapy per this protocol will be offered

• Patients must be within one year of identification of relapse or if beyond that time period, must have at least 10% donor DNA by RFLP or cytogenetics.

• Same allogeneic donor (sibling or URD) used for transplantation is available for lymphocyte donation.

• No severe organ damage (by laboratory or clinical assessment) as measured by:

• - blood creatinine ≤ 2.0 mg/dL

• - liver function tests < 5 x normal

• - left ventricular ejection fraction > 40% (testing required only if symptomatic or prior known impairment).

• - pulmonary functions > 50% (testing required only if symptomatic or prior known impairment). Oxygen saturation (>92%) can be used in child where PFT's cannot be obtained.

• - chest x-ray without evidence of active infection

• Off prednisone and other immunosuppressive agents (given for any reason) for at least 3 days prior to DLI infusions.

• Performance status ≥ 60%

• Women must not be pregnant or lactating. The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy

• Women of childbearing potential and sexually active males are strongly advised to use an accepted and effective method of contraception

• Patient must given written informed consent indicating understanding of the nature of the treatment and its potential risks

Exclusion Criteria:

• Concurrent signs of acute or chronic graft-versus-host disease requiring ongoing treatment at the time of relapse will be ineligible.

• Patients being treated for GVHD with prednisone, cyclosporine, Imuran or other immunosuppressive medications are not eligible until these medications are discontinued for at least 2 weeks without a flare of GVHD.

• Active CNS leukemia

• Active fungal infection or pulmonary infiltrates (stable prior treated disease is allowable)

• HIV positive