Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Bone Marrow Transplantation in Treating Patients With Leukemia

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III, Phase II Treatment Closed Under 46 Other UMN-MT-1995-06 UMN-9224, UMN-MT-9506, NCI-V00-1605, NCT00006451

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.

Entry 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

Prior/Concurrent Therapy:

No prior bone marrow transplantation
No prior radiotherapy that precludes total body 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 

Expected Enrollment

A total of 280 patients/arm will be accrued for this study over 4 years.

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.

Trial Contact Information

Trial Lead Organizations

Masonic Cancer Center at University of Minnesota

John Wagner, MD, Protocol chair		Ph: 612-626-2961; 888-226-2376

Registry Information
Official Title		T-CELL DEPLETION IN UNRELATED DONOR MARROW TRANSPLANTATION
Trial Start Date		1995-03-01
Registered in ClinicalTrials.gov		NCT00006451
Date Submitted to PDQ		1995-01-23
Information Last Verified		2007-05-08
NCI Grant/Contract Number		N01-HB47095