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Post Transplant Donor Lymphocyte Infusion

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00167180
Recruitment Status : Terminated (Accrual Goal Met)
First Posted : September 14, 2005
Results First Posted : July 11, 2017
Last Update Posted : July 30, 2019
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

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.

Condition or disease Intervention/treatment Phase
Leukemia, Myeloid, Chronic Lymphomas Multiple Myeloma Myelodysplastic Syndrome Leukemia, Lymphocytic, Acute Leukemia, Lymphocytic, Chronic AML Procedure: Donor Lymphocyte Infusion Drug: Induction Chemotherapy Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 57 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Use of Cyclophosphamide/Fludarabine to Promote in Vivo Expansion of Donor Lymphocyte Infusions (DLI) to Enhance Efficacy After Allogeneic Transplant
Study Start Date : January 2004
Actual Primary Completion Date : November 21, 2017
Actual Study Completion Date : December 24, 2018

Arm Intervention/treatment
Active Comparator: CML
Patients with Chronic Myelogenous Leukemia (CML) who have failed or refused Gleevec(TM) therapy and will receive Donor Lymphocyte Infusion.
Procedure: Donor Lymphocyte Infusion
donor cells infused over 2 hrs at cell dose of 0.5 dx 10^8 CD3+T-cells/kg
Other Name: DLI

Active Comparator: 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.
Procedure: Donor Lymphocyte Infusion
donor cells infused over 2 hrs at cell dose of 0.5 dx 10^8 CD3+T-cells/kg
Other Name: DLI

Drug: Induction Chemotherapy
Fludarabine 25 mg/m2 IV Cyclosphosphamide 60 mg/kg IV
Other Names:
  • Fludara
  • Endoxan, Cytoxan, Neosar, Procytox, Revimmune, cytophosphane

Primary Outcome Measures :
  1. Number of Patients Alive [ Time Frame: 1 Year ]

    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.

Secondary Outcome Measures :
  1. Number of Patients Alive Without Disease [ Time Frame: 1 Year ]
    The number of patients alive one year after treatment without any signs or symptoms of the cancer being treated or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works.

  2. Number of Participants With Complete Remission [ Time Frame: one year ]
    In complete remission, all signs and symptoms of cancer that can be detected with modern technology have disappeared, although cancer still may be in the body.

  3. Number of Patients With Acute Graft-Versus-Host Disease [ Time Frame: Day 100 ]
    Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.

  4. Number of Patients With Bone Marrow Aplasia [ Time Frame: Day 100 ]

    Aplastic anemia is a disorder in which the bone marrow greatly decreases or stops production of blood cells.

    In aplastic anemia, the basic structure of the marrow becomes abnormal, and those cells responsible for generating blood cells (hematopoietic cells) are greatly decreased in number or absent. These hematopoietic cells are replaced by large quantities of fat.

Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00167180

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United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
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Principal Investigator: Jeffrey Miller, MD Masonic Cancer Center, University of Minnesota
  Study Documents (Full-Text)

Documents provided by Masonic Cancer Center, University of Minnesota:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Masonic Cancer Center, University of Minnesota Identifier: NCT00167180    
Obsolete Identifiers: NCT00303693
Other Study ID Numbers: 2004LS006
MT2003-15 ( Other Identifier: Blood and Marrow Transplantation Program )
0401M55207 ( Other Identifier: IRB, University of Minnesota )
First Posted: September 14, 2005    Key Record Dates
Results First Posted: July 11, 2017
Last Update Posted: July 30, 2019
Last Verified: July 2019
Keywords provided by Masonic Cancer Center, University of Minnesota:
donor lymphocyte infusions
bone marrow transplant
Additional relevant MeSH terms:
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Multiple Myeloma
Leukemia, Myeloid
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Lymphatic Diseases
Leukemia, B-Cell
Myeloproliferative Disorders
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents