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Post Transplant Donor Lymphocyte Infusion

Primary Purpose

Leukemia, Myeloid, Chronic, Lymphomas, Multiple Myeloma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Donor Lymphocyte Infusion
Induction Chemotherapy
Sponsored by
Masonic Cancer Center, University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Myeloid, Chronic focused on measuring donor lymphocyte infusions, BMT, bone marrow transplant

Eligibility Criteria

1 Year - 70 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Masonic Cancer Center, University of Minnesota

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

CML

Non-CML or CML that Relapsed after Donor Lymphocyte Infusion

Arm Description

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

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

Outcomes

Primary Outcome Measures

Number of Patients Alive
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

Number of Patients Alive Without Disease
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.
Number of Participants With Complete Remission
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.
Number of Patients With Acute Graft-Versus-Host Disease
Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
Number of Patients With Bone Marrow Aplasia
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.

Full Information

First Posted
September 9, 2005
Last Updated
July 10, 2019
Sponsor
Masonic Cancer Center, University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT00167180
Brief Title
Post Transplant Donor Lymphocyte Infusion
Official Title
Use of Cyclophosphamide/Fludarabine to Promote in Vivo Expansion of Donor Lymphocyte Infusions (DLI) to Enhance Efficacy After Allogeneic Transplant
Study Type
Interventional

2. Study Status

Record Verification Date
July 2019
Overall Recruitment Status
Terminated
Why Stopped
Accrual Goal Met
Study Start Date
January 2004 (undefined)
Primary Completion Date
November 21, 2017 (Actual)
Study Completion Date
December 24, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myeloid, Chronic, Lymphomas, Multiple Myeloma, Myelodysplastic Syndrome, Leukemia, Lymphocytic, Acute, Leukemia, Lymphocytic, Chronic, AML
Keywords
donor lymphocyte infusions, BMT, bone marrow transplant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
57 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CML
Arm Type
Active Comparator
Arm Description
Patients with Chronic Myelogenous Leukemia (CML) who have failed or refused Gleevec(TM) therapy and will receive Donor Lymphocyte Infusion.
Arm Title
Non-CML or CML that Relapsed after Donor Lymphocyte Infusion
Arm Type
Active Comparator
Arm Description
Patients with non-CML or CML who have failed Donor Lymphocyte Infusion (DLI) and will receive induction chemotherapy plus DLI.
Intervention Type
Procedure
Intervention Name(s)
Donor Lymphocyte Infusion
Other Intervention Name(s)
DLI
Intervention Description
donor cells infused over 2 hrs at cell dose of 0.5 dx 10^8 CD3+T-cells/kg
Intervention Type
Drug
Intervention Name(s)
Induction Chemotherapy
Other Intervention Name(s)
Fludara, Endoxan, Cytoxan, Neosar, Procytox, Revimmune, cytophosphane
Intervention Description
Fludarabine 25 mg/m2 IV Cyclosphosphamide 60 mg/kg IV
Primary Outcome Measure Information:
Title
Number of Patients Alive
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.
Time Frame
1 Year
Secondary Outcome Measure Information:
Title
Number of Patients Alive Without Disease
Description
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.
Time Frame
1 Year
Title
Number of Participants With Complete Remission
Description
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.
Time Frame
one year
Title
Number of Patients With Acute Graft-Versus-Host Disease
Description
Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
Time Frame
Day 100
Title
Number of Patients With Bone Marrow Aplasia
Description
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.
Time Frame
Day 100

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jeffrey Miller, MD
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
Masonic Cancer Center, University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
17579184
Citation
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.
Results Reference
derived

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Post Transplant Donor Lymphocyte Infusion

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