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Use of Cyclophosphamide/Fludarabine to Promote in Vivo Expansion of Donor Lymphocyte Infusions (DLI) to Enhance Efficacy After Allogeneic Transplant

Phase 2
1 Year
70 Years
Open (Enrolling)
Leukemia, Myeloid, Chronic, Lymphomas, Multiple Myeloma, Myelodysplastic Syndrome, Leukemia, Lymphocytic, Acute, Leukemia, Lymphocytic, Chronic, AML

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Trial Information

Use of Cyclophosphamide/Fludarabine to Promote in Vivo Expansion of Donor Lymphocyte Infusions (DLI) to Enhance Efficacy After Allogeneic Transplant

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.

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

- - 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

- HIV positive

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Overall survival

Outcome Description:

The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease, such as cancer. Also called survival rate. Overall survival will be defined as time from date of enrollment to date of death or censored at the date of last documented contact for patients still alive.

Outcome Time Frame:

1 Year

Safety Issue:


Principal Investigator

Jeffrey Miller, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Masonic Cancer Center, University of Minnesota


United States: Institutional Review Board

Study ID:




Start Date:

January 2004

Completion Date:

December 2014

Related Keywords:

  • Leukemia, Myeloid, Chronic
  • Lymphomas
  • Multiple Myeloma
  • Myelodysplastic Syndrome
  • Leukemia, Lymphocytic, Acute
  • Leukemia, Lymphocytic, Chronic
  • AML
  • donor lymphocyte infusions
  • BMT
  • bone marrow transplant
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Lymphoma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Myelodysplastic Syndromes
  • Preleukemia



Masonic Cancer Center, University of Minnesota Minneapolis, Minnesota  55455