Post Transplant Donor Lymphocyte Infusion

NCT ID: NCT00167180

Last Updated: 2019-07-30

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 57 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-01-31
• Study Completion Date: 2018-12-24

Brief 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.

Detailed Description

When cancer relapses after donor bone marrow transplantation, regular dose chemotherapy offers little hope of prolonged survival. However, there is evidence that lymphocytes can attack cancer cells. There is considerable evidence that this immune attack on cancer cells is associated with graft-versus-host disease. Although graft-versus-host disease can cause problems, this immune reaction may, in part, be the way that bone marrow transplantation cures cancer. In this study we hope that infusion of immune cells from the subject's bone marrow donor plus a chemotherapy regimen of cyclophosphamide and fludarabine will activate the subject's immune system to attack their cancer.

Conditions

Leukemia, Myeloid, Chronic; Lymphomas; Multiple Myeloma; Myelodysplastic Syndrome; Leukemia, Lymphocytic, Acute; Leukemia, Lymphocytic, Chronic; AML

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CML

Patients with Chronic Myelogenous Leukemia (CML) who have failed or refused Gleevec(TM) therapy and will receive Donor Lymphocyte Infusion.

Group Type: ACTIVE_COMPARATOR

Donor Lymphocyte Infusion

Intervention Type: PROCEDURE

donor cells infused over 2 hrs at cell dose of 0.5 dx 10\^8 CD3+T-cells/kg

Non-CML or CML that Relapsed after Donor Lymphocyte Infusion

Patients with non-CML or CML who have failed Donor Lymphocyte Infusion (DLI) and will receive induction chemotherapy plus DLI.

Group Type: ACTIVE_COMPARATOR

Donor Lymphocyte Infusion

Intervention Type: PROCEDURE

donor cells infused over 2 hrs at cell dose of 0.5 dx 10\^8 CD3+T-cells/kg

Induction Chemotherapy

Intervention Type: DRUG

Fludarabine 25 mg/m2 IV Cyclosphosphamide 60 mg/kg IV

Interventions

Donor Lymphocyte Infusion

donor cells infused over 2 hrs at cell dose of 0.5 dx 10\^8 CD3+T-cells/kg

Intervention Type: PROCEDURE

Induction Chemotherapy

Fludarabine 25 mg/m2 IV Cyclosphosphamide 60 mg/kg IV

Intervention Type: DRUG

Other Intervention Names

DLI; Fludara; Endoxan, Cytoxan, Neosar, Procytox, Revimmune, cytophosphane

Eligibility 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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jeffrey Miller, MD

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Countries

United States

References

Miller JS, Weisdorf DJ, Burns LJ, Slungaard A, Wagner JE, Verneris MR, Cooley S, Wangen R, Fautsch SK, Nicklow R, Defor T, Blazar BR. Lymphodepletion followed by donor lymphocyte infusion (DLI) causes significantly more acute graft-versus-host disease than DLI alone. Blood. 2007 Oct 1;110(7):2761-3. doi: 10.1182/blood-2007-05-090340. Epub 2007 Jun 19.

Reference Type: DERIVED

PMID: 17579184 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MT2003-15

Identifier Type: OTHER

Identifier Source: secondary_id

0401M55207

Identifier Type: OTHER

Identifier Source: secondary_id

2004LS006

Identifier Type: -

Identifier Source: org_study_id

NCT00303693

Identifier Type: -

Identifier Source: nct_alias