Post Transplant Donor Lymphocyte Infusion

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Masonic Cancer Center, University of Minnesota
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00167180
First received: September 9, 2005
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Leukemia, Myeloid, Chronic
Lymphomas
Multiple Myeloma
Myelodysplastic Syndrome
Leukemia, Lymphocytic, Acute
Leukemia, Lymphocytic, Chronic
AML
Procedure: Donor Lymphocyte Infusion
Drug: Induction Chemotherapy + DLI
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Overall survival [ Time Frame: 1 Year ] [ Designated as safety issue: No ]

    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:
  • Disease-free Survival [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    The length of time after treatment ends that a patient survives without any signs or symptoms of that cancer 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.

  • Complete Remission [ Time Frame: one year ] [ Designated as safety issue: No ]
    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.

  • Acute Graft-Versus-Host Disease [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
    Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.

  • Bone marrow aplasia [ Time Frame: Day 100 ] [ Designated as safety issue: No ]

    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.



Estimated Enrollment: 57
Study Start Date: January 2004
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Chronic Myelogenous Leukemia
Patients who have failed for 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-Chronic Myelogenous Leukemia
Patients with non-CML or CML who have failed DLI and will receive Induction Chemotherapy + DLI.
Drug: Induction Chemotherapy + DLI
Fludarabine 25 mg/m2 IV Cyclosphosphamide 60 mg/kg IV Donor Lymphocyte Infusion (DLI)
Other Names:
  • Fludara
  • Endoxan, Cytoxan, Neosar, Procytox, Revimmune, cytophosphane

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.

  Eligibility

Ages Eligible for Study:   1 Year to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00167180

Contacts
Contact: Jeffrey Miller, M.D. 612-625--3636 mille011@umn.edu

Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Jeffrey Miller, MD    612-625-3636    mille011@umn.edu   
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Jeffrey Miller, MD Masonic Cancer Center, University of Minnesota
  More Information

No publications provided by Masonic Cancer Center, University of Minnesota

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00167180     History of Changes
Obsolete Identifiers: NCT00303693
Other Study ID Numbers: 2004LS006, MT2003-15, 0401M55207
Study First Received: September 9, 2005
Last Updated: May 15, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Masonic Cancer Center, University of Minnesota:
donor lymphocyte infusions
BMT
bone marrow transplant

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Myelodysplastic Syndromes
Preleukemia
Leukemia, Myeloid
Leukemia, Lymphoid
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Bone Marrow Diseases
Precancerous Conditions
Lymphatic Diseases
Leukemia, B-Cell
Myeloproliferative Disorders

ClinicalTrials.gov processed this record on September 22, 2014