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, Myelodysplasia, or Lymphoblastic Lymphoma

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase III, Phase II Treatment Closed 55 and under NCI MCV-CCHR-9504-2X DUMC-75951, NCI-G98-1388, NCT00003187

Objectives

I.   Compare the disease free survival of patients with leukemia, 
myelodysplasia, or lymphoblastic lymphoma after treatment with conventional 
(non-T cell depleted) or T cell depleted unrelated donor bone marrow 
transplantation.

II.  Compare the incidence of primary and secondary graft failure, acute and 
chronic graft-vs-host disease, complications (infection, veno-occlusive 
disease, interstitial pneumonitis), and relapse in these patients after these 
treatments.

III. Compare the incidence of other malignancies, lymphoproliferative 
disorders, and post-transplant myelodysplasia in these patients after these 
treatments.

Entry Criteria

Disease Characteristics:

Pathologically confirmed acute myeloid leukemia
 Not in first complete remission with translocations t(8;21) unless failed
  first line induction therapy
 Not in first complete remission with translocations t(15;17) or 16q
  abnormality unless:
   Failed first line induction therapy OR
   Molecular evidence of disease

Pathologically confirmed acute lymphoblastic lymphoma (ALL)
 Not in first complete remission OR
 High risk ALL in first complete remission defined as: 
  Hypodiploidy OR
  Pseudodiploidy with translocations t(9,22), t(4;11), or t(8;14) OR
  Elevated WBC at presentation
   Greater than 100,000/mm3 if 6-12 months old
   Greater than 50,000/mm3 if 10-20 years old
   Greater than 20,000/mm3 if 21 or over OR
  Failed to achieve complete remission after 4 weeks of induction therapy

Pathologically confirmed chronic myelogenous leukemia (CML) not in blast
crisis

Pathologically confirmed undifferentiated leukemia or biphenotypic leukemia

Pathologically confirmed juvenile CML with or without either 7q- or infantile
monosomy 7
 Leukocytosis with absolute monocytosis greater than 450 microliters AND
 Immature myeloid cells in peripheral blood circulation
 Less than 25% marrow blasts

Myelodysplastic syndromes: 
 Refractory anemia (RA)
 RA with ringed sideroblasts
 RA with excess blasts (RAEB)
 RAEB in transformation
 Chronic myelomonocytic leukemia

Pathologically confirmed stage IV lymphoblastic lymphoma

No active CNS or skin leukemic involvement

No consenting suitably HLA-matched related donor available

Consenting unrelated donor available

Prior/Concurrent Therapy:

Biologic therapy:
 No prior autologous or allogeneic bone marrow transplant

Chemotherapy:
 See Disease Characteristics

Endocrine therapy:
 Not specified

Radiotherapy:
 No concurrent mediastinal radiation
 No prior radiation therapy that would preclude total body irradiation

Surgery:
 Not specified

Patient Characteristics:

Age:
 55 and under

Performance status:
 Karnofsky 70-100% OR
 Lansky 60-100%

Life expectancy:
 Not specified

Hematopoietic:
 See Disease Characteristics

Hepatic:
 Bilirubin less than 2.5 mg/dL
 SGOT less than 3 times upper limit of normal

Renal:
 Creatinine within normal range OR
 Creatinine clearance greater than 60 mL/min

Cardiovascular:
 Asymptomatic OR
 Left ventricular ejection fraction at rest greater than 40% and improves with
  exercise

Pulmonary:
 Asymptomatic OR
 DLCO greater than 45%

Other:
 Not pregnant or lactating
 HIV negative
 No uncontrolled viral, bacterial, or fungal infection

Expected Enrollment

 A total of 560 patients will be accrued for this study within 4 years.

Outline

This is a randomized, multicenter study.  Patients will be stratified 
according to institution.

Patients are assigned to one of two treatment arms, one with conventional bone 
marrow transplantation (arm I) and one with T cell depletion of the bone 
marrow (arm II).

Arm I:  Patients receive cyclophosphamide on days -6 and -5.  Total body 
irradiation (TBI) is administered on days -4 to 0, although this order may be 
reversed.  Males with ALL receive a testicular boost of radiation therapy.  
Bone marrow is infused on day 0.  Patients receive cyclosporine beginning on 
day -1 and methotrexate IV on days 1, 3, 6, and 11. 

Arm II:  T cell depletion is conducted by 2 different methods, according to 
the institution, and treatment varies depending on the method used.  Method I 
is by T10B9 depletion and Method II is by counterflow elutriation depletion.

 Method I:  Depending on the institution, some patients receive TBI on days -9
 to -7 (before chemotherapy) (Course I) and some receive TBI on days -3 to -1
 (after chemotherapy) (Course II).  Course I also includes cytarabine IV on
 days -5 to -3, cyclophosphamide IV on days -2 and -1, and methylprednisolone
 IV on days -2 to 0 and 5-18.  Bone marrow infusion is administered on day 0.
 Cyclosporine begins on day -1.  Course II includes cytarabine IV on days -7
 to -4 and cyclophosphamide on days -6 to -5.  Methylprednisolone IV is
 administered on days -2 to 0 and 5-18.  Bone marrow infusion is administered
 on day 0.  Cyclosporine begins on day 0.

 Method II:  Preparative therapy varies according to the disease category.
  Acute lymphoblastic leukemia:  Patients undergo TBI on days -7 to -4.  Males
  receive testicular boost on day -7, and all receive electron boost to
  anterior and posterior chest wall on days -5 and -4.  Cyclophosphamide IV
  is administered on days -3 and -2.  Bone marrow infusion is administered on
  day 0.

  Acute nonlymphocytic leukemia, chronic myelogenous leukemia, and
  myelodysplastic syndrome:  Patients receive cyclophosphamide IV on days -7
  and -6, followed by TBI on days -4 to -1.  Bone marrow infusion is
  administered on day 0.

  Patients receive methylprednisolone IV every 12 hr on days -2,-1, and 5-19.
  Cyclosporine is administered from day -3 to day 180.

All patients on both arms receive filgrastim (granulocyte colony-stimulating 
factor; G-CSF) beginning on day 7 post-transplant.

Patients are followed weekly for the first 14 weeks, at day 100, every 6 
months for 2 years, then annually thereafter.

Trial Contact Information

Trial Lead Organizations

Virginia Commonwealth University Massey Cancer Center

Lee Ann Jensen, PhD, Protocol chair		Ph: 301-435-0066

Registry Information
Official Title		The Unrelated Donor Marrow Transplantation Trial
Trial Start Date		1995-05-22
Registered in ClinicalTrials.gov		NCT00003187
Date Submitted to PDQ		1998-01-14
Information Last Verified		2007-07-11
NCI Grant/Contract Number		CA16059