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Bone Marrow Transplantation in Treating Patients With Leukemia

Primary Purpose

Graft Versus Host Disease, Leukemia, Lymphoma

Status
Withdrawn
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
anti-thymocyte globulin
cyclophosphamide
cyclosporine
methotrexate
methylprednisolone
allogeneic bone marrow transplantation
in vitro-treated bone marrow transplantation
radiation therapy
Sponsored by
Masonic Cancer Center, University of Minnesota
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Graft Versus Host Disease focused on measuring recurrent childhood acute lymphoblastic leukemia, stage IV childhood lymphoblastic lymphoma, recurrent childhood acute myeloid leukemia, recurrent adult acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, chronic phase chronic myelogenous leukemia, accelerated phase chronic myelogenous leukemia, adult acute lymphoblastic leukemia in remission, childhood acute lymphoblastic leukemia in remission, acute undifferentiated leukemia, stage IV adult lymphoblastic lymphoma, graft versus host disease

Eligibility Criteria

undefined - 45 Years (Child, Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Acute myelocytic leukemia with or without history of myelodysplastic syndrome Not in first complete remission (i.e., greater than 5% blasts in marrow) with t(8;21), t(15;17), or 16q abnormality unless failure on first-line induction therapy Acute lymphocytic leukemia (ALL) in one of the following categories: In second or third complete remission (CR) High-risk ALL in first CR, with high risk defined as: Hypodiploidy OR pseudodiploidy with t(9;22), t(4;11), or t(8;14) Failure to achieve CR after 4 weeks of induction therapy Elevated WBC at presentation, i.e.: Greater than 100,000 in patients aged 6 to 12 months Greater than 200,000 in patients aged 1 to 20 years Greater than 20,000 in patients aged 21 to 44 years Chronic myelogenous leukemia not in blast crisis (i.e., no greater than 30% promyelocytes plus blasts in bone marrow) Stage IV lymphoblastic lymphoma Undifferentiated or biphenotypic leukemia Unrelated donor available Patients aged 35 and younger: HLA-A, and -B serologic identity and HLA-DRB1 identity by high-resolution DNA typing OR Single HLA-A or -B serologic mismatch with DRB1 identity by high-resolution DNA typing OR HLA-A and -B serologic identity with single DRB1 mismatch by high- or low- resolution DNA typing Patients aged 36 to 44: HLA-A and -B serologic identity and HLA-DRB1 identity by high-resolution DNA typing The following exclude: Relapse 12 months after discontinuing therapy in patients aged 1 to 10 years who are in second remission Active central nervous system or leukemic skin involvement Requirement for additional mediastinal irradiation PATIENT CHARACTERISTICS: Age: Under 46 Performance status: Karnofsky 70-100% Lansky 50-100% Hematopoietic: See Disease Characteristics Hepatic: Bilirubin less than 2.5 mg/dL AST less than 3 times normal Renal: Creatinine normal OR Creatinine clearance greater than 60 mL/min Cardiovascular: Asymptomatic OR Resting LVEF greater than 40% and improves with exercise Pulmonary: Asymptomatic OR DLCO greater than 45% of predicted (corrected for hemoglobin) Other: HIV negative No uncontrolled viral, bacterial, or fungal infection Not pregnant or nursing PRIOR CONCURRENT THERAPY: No prior bone marrow transplantation No prior radiotherapy that precludes total body irradiation

Sites / Locations

  • University of Minnesota Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 6, 2000
Last Updated
December 31, 2019
Sponsor
Masonic Cancer Center, University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT00006451
Brief Title
Bone Marrow Transplantation in Treating Patients With Leukemia
Official Title
T-cell Depletion In Unrelated Donor Marrow Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
November 2017
Overall Recruitment Status
Withdrawn
Why Stopped
Terminated (due to no accrual)
Study Start Date
April 1996 (undefined)
Primary Completion Date
November 2000 (Actual)
Study Completion Date
November 2000 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Masonic Cancer Center, University of Minnesota

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy used to kill cancer cells. PURPOSE: Randomized phase II/III trial to determine the effectiveness of bone marrow transplantation in treating patients who have leukemia.
Detailed Description
OBJECTIVES: I. Compare unrelated donor bone marrow transplantation using T-cell-depleted marrow versus unmodified marrow in adults and children with leukemia. II. Evaluate 2-year leukemia-free survival, primary and secondary graft failure, graft-versus-host disease, infection, and relapse in these patients. III. Assess the quality of life associated with T-cell-depleted versus unmodified, unrelated donor transplantation. OUTLINE: This is a randomized, multicenter study. Patients are stratified by center. Patients receive myeloablative therapy according to diagnosis: those with acute lymphocytic leukemia and lymphoblastic lymphoma are treated with total body irradiation (TBI), with a testicular and chest wall boost as appropriate, followed by cyclophosphamide (CTX); patients with undifferentiated or biphenotypic leukemia or with acute or chronic myelocytic leukemia are treated with CTX followed by TBI. Patients are then randomly assigned to receive non-T-cell-depleted, unrelated marrow versus T-cell-depleted, unrelated marrow. The modified marrow is depleted of T-lymphocytes by counterflow elutriation and positively selected for CD34 cells. Graft-versus-host disease (GVHD) prophylaxis with cyclosporine and methotrexate is given to the unmodified marrow group. Patients who receive modified marrow are given antithymocyte globulin (or methylprednisolone) for graft rejection prophylaxis before transplantation and cyclosporine and methylprednisolone for GVHD prophylaxis after transplantation.

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
Keywords
recurrent childhood acute lymphoblastic leukemia, stage IV childhood lymphoblastic lymphoma, recurrent childhood acute myeloid leukemia, recurrent adult acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, chronic phase chronic myelogenous leukemia, accelerated phase chronic myelogenous leukemia, adult acute lymphoblastic leukemia in remission, childhood acute lymphoblastic leukemia in remission, acute undifferentiated leukemia, stage IV adult lymphoblastic lymphoma, graft versus host disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Allocation
Randomized
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
anti-thymocyte globulin
Intervention Type
Drug
Intervention Name(s)
cyclophosphamide
Intervention Type
Drug
Intervention Name(s)
cyclosporine
Intervention Type
Drug
Intervention Name(s)
methotrexate
Intervention Type
Drug
Intervention Name(s)
methylprednisolone
Intervention Type
Procedure
Intervention Name(s)
allogeneic bone marrow transplantation
Intervention Type
Procedure
Intervention Name(s)
in vitro-treated bone marrow transplantation
Intervention Type
Procedure
Intervention Name(s)
radiation therapy

10. Eligibility

Sex
All
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Acute myelocytic leukemia with or without history of myelodysplastic syndrome Not in first complete remission (i.e., greater than 5% blasts in marrow) with t(8;21), t(15;17), or 16q abnormality unless failure on first-line induction therapy Acute lymphocytic leukemia (ALL) in one of the following categories: In second or third complete remission (CR) High-risk ALL in first CR, with high risk defined as: Hypodiploidy OR pseudodiploidy with t(9;22), t(4;11), or t(8;14) Failure to achieve CR after 4 weeks of induction therapy Elevated WBC at presentation, i.e.: Greater than 100,000 in patients aged 6 to 12 months Greater than 200,000 in patients aged 1 to 20 years Greater than 20,000 in patients aged 21 to 44 years Chronic myelogenous leukemia not in blast crisis (i.e., no greater than 30% promyelocytes plus blasts in bone marrow) Stage IV lymphoblastic lymphoma Undifferentiated or biphenotypic leukemia Unrelated donor available Patients aged 35 and younger: HLA-A, and -B serologic identity and HLA-DRB1 identity by high-resolution DNA typing OR Single HLA-A or -B serologic mismatch with DRB1 identity by high-resolution DNA typing OR HLA-A and -B serologic identity with single DRB1 mismatch by high- or low- resolution DNA typing Patients aged 36 to 44: HLA-A and -B serologic identity and HLA-DRB1 identity by high-resolution DNA typing The following exclude: Relapse 12 months after discontinuing therapy in patients aged 1 to 10 years who are in second remission Active central nervous system or leukemic skin involvement Requirement for additional mediastinal irradiation PATIENT CHARACTERISTICS: Age: Under 46 Performance status: Karnofsky 70-100% Lansky 50-100% Hematopoietic: See Disease Characteristics Hepatic: Bilirubin less than 2.5 mg/dL AST less than 3 times normal Renal: Creatinine normal OR Creatinine clearance greater than 60 mL/min Cardiovascular: Asymptomatic OR Resting LVEF greater than 40% and improves with exercise Pulmonary: Asymptomatic OR DLCO greater than 45% of predicted (corrected for hemoglobin) Other: HIV negative No uncontrolled viral, bacterial, or fungal infection Not pregnant or nursing PRIOR CONCURRENT THERAPY: No prior bone marrow transplantation No prior radiotherapy that precludes total body irradiation
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John E. Wagner, MD
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Study Chair
Facility Information:
Facility Name
University of Minnesota Cancer Center
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States

12. IPD Sharing Statement

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Bone Marrow Transplantation in Treating Patients With Leukemia

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