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Donor T Cells in Treating Patients With High-Risk Hematologic Cancer Undergoing Donor Peripheral Blood Stem Cell Transplant

Primary Purpose

Graft Versus Host Disease, Leukemia, Lymphoma

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CD4+CD25+ regulatory T cells
allogeneic hematopoietic stem cell transplantation
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 Graft Versus Host Disease focused on measuring graft versus host disease, adult acute lymphoblastic leukemia in remission, adult acute myeloid leukemia in remission, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), chronic phase chronic myelogenous leukemia, accelerated phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma, stage III adult Burkitt lymphoma, stage III adult diffuse large cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage III mantle cell lymphoma, stage III marginal zone lymphoma, stage III small lymphocytic lymphoma, stage IV adult Burkitt lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV mantle cell lymphoma, stage IV marginal zone lymphoma, stage IV small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, recurrent adult acute lymphoblastic leukemia, recurrent childhood acute myeloid leukemia, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of a high-risk hematologic malignancy, including any of the following:

    • Acute lymphocytic leukemia
    • Acute myelocytic leukemia
    • Chronic myelogenous leukemia
    • Myelodysplastic syndrome
    • Non-Hodgkin lymphoma
    • Multiple myeloma

  • Meet eligibility criteria and co-enrolled in one of the following University of Minnesota protocols:

    • MT2001-02 consisting of myeloablative prep (cyclophosphamide and total body irradiation) followed by HLA-identical sibling peripheral blood progenitor cells (PBPC) transplantation
    • MT2001-10 consisting of nonmyeloablative prep (cyclophosphamide, fludarabine and total body irradiation) followed by HLA-identical sibling PBPC transplantation
  • Voluntarily written informed consent

  • Must have an HLA-identical sibling donor available, meeting the following criteria:

    • 12 to 75 years of age, >40 kg body weight and in good health
    • Matched to recipient for HLA-A, B,DRB1 identical sibling match to recipient
    • Must be able and willing to have a separate apheresis collection performed on day -21 for the purposes of this study (in addition to the apheresis required for the transplant protocol)
    • Human immunodeficiency virus nucleic acid testing (HIV-NAT) negative, Human T-lymphotropic virus 1 (HTLV-1), HTLV-2 negative, hepatitic B and C negative

Exclusion Criteria:

  • Not pregnant or nursing

Sites / Locations

  • Masonic Cancer Center, University of Minnesota

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Patients Receiving CD4+/CD25+ cells

Arm Description

CD4+/CD25+ cells given intravenously over 15-60 minutes on Day -2 (prior to peripheral blood progenitor cell transplant)

Outcomes

Primary Outcome Measures

Maximum tolerated dose of CD4+CD25+ cells/kg (phase I)
Incidence of grade 3-5 infusional toxicity (phase II)

Secondary Outcome Measures

Cumulative incidence of grade II-IV acute graft-versus-host-disease (GVHD)
Incidence of chronic graft-versus-host disease (GVHD)
Incidence of Relapse
Overall Survival
Disease-free survival

Full Information

First Posted
July 29, 2008
Last Updated
November 27, 2017
Sponsor
Masonic Cancer Center, University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT00725062
Brief Title
Donor T Cells in Treating Patients With High-Risk Hematologic Cancer Undergoing Donor Peripheral Blood Stem Cell Transplant
Official Title
Phase I-II Dose Escalation Study of CD4+CD25+ Cells in Adult Patients Undergoing HLA-Identical Sibling Donor Peripheral Blood Progenitor Cell Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Terminated
Why Stopped
Slow accrual.
Study Start Date
June 2008 (undefined)
Primary Completion Date
April 2010 (Actual)
Study Completion Date
April 2010 (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
RATIONALE: A donor peripheral stem cell transplant helps stop the growth of cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them. Giving an infusion of donor T cells may helps stop the patient's immune system from rejecting the donor's stem cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of donor T cells in treating patients with high-risk hematologic cancer who are undergoing donor peripheral blood stem cell transplant. Note: Only Phase I portion of study was performed. Due to slow accrual, study was closed before Phase II portion of study.
Detailed Description
OBJECTIVES: Primary To determine the maximum tolerated dose (MTD) of CD4+/CD25+ cells that can be safely administered to patients undergoing HLA-identical sibling donor Peripheral Blood Progenitor Cell (PBPC) transplantation. To determine whether CD4+ and CD25+ cells can be safely administered to patients with high-risk hematologic malignancies undergoing HLA-identical sibling donor PBPC transplantation. Secondary To determine the incidence of grade II-IV acute graft-versus-host-disease (GVHD), chronic GVHD, relapse, and survival after administration of CD4+ and CD25+ regulatory T cells in these patients. OUTLINE: This is a dose-escalation study of CD4+ and CD25+ donor regulatory T cells followed by a phase II study. All patients receive myeloablative preparative therapy and GVHD prophylaxis as per University of Minnesota protocol UMN-MT2001-02 or UMN-MT2001-10. First allogeneic peripheral blood progenitor cell (PBPC) infusion: Patients receive unmobilized, culture-expanded, CD4- and CD25-positive donor regulatory T cells IV over 15-60 minutes at the assigned dose on day -2. Second allogeneic PBPC infusion: Patients undergo matched-sibling donor PBPC transplantation IV on day 0. Patients undergo blood sample collection prior to commencement of preparative therapy and then at day 100, 6 months, and 1 year after PBPC transplantation. Samples are analyzed for immune reconstitution by immunophenotyping and functional analyses. After completion of study therapy, patients are followed for up to 1 year.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graft Versus Host Disease, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes
Keywords
graft versus host disease, adult acute lymphoblastic leukemia in remission, adult acute myeloid leukemia in remission, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), chronic phase chronic myelogenous leukemia, accelerated phase chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, refractory multiple myeloma, stage III adult Burkitt lymphoma, stage III adult diffuse large cell lymphoma, stage III adult diffuse mixed cell lymphoma, stage III adult diffuse small cleaved cell lymphoma, stage III adult immunoblastic large cell lymphoma, stage III adult lymphoblastic lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage III mantle cell lymphoma, stage III marginal zone lymphoma, stage III small lymphocytic lymphoma, stage IV adult Burkitt lymphoma, stage IV adult diffuse large cell lymphoma, stage IV adult diffuse mixed cell lymphoma, stage IV adult diffuse small cleaved cell lymphoma, stage IV adult immunoblastic large cell lymphoma, stage IV adult lymphoblastic lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, stage IV mantle cell lymphoma, stage IV marginal zone lymphoma, stage IV small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, recurrent adult acute lymphoblastic leukemia, recurrent childhood acute myeloid leukemia, recurrent adult Burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Patients Receiving CD4+/CD25+ cells
Arm Type
Experimental
Arm Description
CD4+/CD25+ cells given intravenously over 15-60 minutes on Day -2 (prior to peripheral blood progenitor cell transplant)
Intervention Type
Biological
Intervention Name(s)
CD4+CD25+ regulatory T cells
Intervention Description
Cohort 1 will receive 3 x 10^6 CD4+CD25+ cells/kg, Cohort 2 will receive 1 x 10^7 CD4+CD25+ cells/kg, Cohort 3 will receive 3 x 10^7 CD4+CD25 cells/kg
Intervention Type
Procedure
Intervention Name(s)
allogeneic hematopoietic stem cell transplantation
Other Intervention Name(s)
peripheral blood progenitor cell (PBPC) transplantation
Intervention Description
Occurs on Day 0 of study - HLA-identical sibling donor peripheral blood progenitor cell (PBPC) transplantation
Primary Outcome Measure Information:
Title
Maximum tolerated dose of CD4+CD25+ cells/kg (phase I)
Time Frame
Day 0 (48 hours post infusion)
Title
Incidence of grade 3-5 infusional toxicity (phase II)
Time Frame
Day 0 (48 hours post infusion)
Secondary Outcome Measure Information:
Title
Cumulative incidence of grade II-IV acute graft-versus-host-disease (GVHD)
Time Frame
Day 100 Post Infusion
Title
Incidence of chronic graft-versus-host disease (GVHD)
Time Frame
Month 6 Post Infusion
Title
Incidence of Relapse
Time Frame
Month 6 Post Infusion
Title
Overall Survival
Time Frame
Day 100 and 1 Year Post Infusion
Title
Disease-free survival
Time Frame
Day 100 and 1 Year Post Infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of a high-risk hematologic malignancy, including any of the following: Acute lymphocytic leukemia Acute myelocytic leukemia Chronic myelogenous leukemia Myelodysplastic syndrome Non-Hodgkin lymphoma Multiple myeloma Meet eligibility criteria and co-enrolled in one of the following University of Minnesota protocols: MT2001-02 consisting of myeloablative prep (cyclophosphamide and total body irradiation) followed by HLA-identical sibling peripheral blood progenitor cells (PBPC) transplantation MT2001-10 consisting of nonmyeloablative prep (cyclophosphamide, fludarabine and total body irradiation) followed by HLA-identical sibling PBPC transplantation Voluntarily written informed consent Must have an HLA-identical sibling donor available, meeting the following criteria: 12 to 75 years of age, >40 kg body weight and in good health Matched to recipient for HLA-A, B,DRB1 identical sibling match to recipient Must be able and willing to have a separate apheresis collection performed on day -21 for the purposes of this study (in addition to the apheresis required for the transplant protocol) Human immunodeficiency virus nucleic acid testing (HIV-NAT) negative, Human T-lymphotropic virus 1 (HTLV-1), HTLV-2 negative, hepatitic B and C negative Exclusion Criteria: Not pregnant or nursing
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Margaret L. MacMillan, 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

Learn more about this trial

Donor T Cells in Treating Patients With High-Risk Hematologic Cancer Undergoing Donor Peripheral Blood Stem Cell Transplant

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