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

Alternate Title

Chemotherapy and Bone Marrow Transplantation in Treating Patients Acute Myeloid With Leukemia or Myelodysplastic Syndrome

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Closed 6 months to 60 years Other WSU-D-696-87 NCI-V93-0345, NCT00002547

Objectives

I.  Determine overall and leukemia-free survival of patients with acute 
nonlymphocytic leukemia or myelodysplastic syndrome treated with busulfan and 
cyclophosphamide (low-risk patients) or cytarabine, busulfan, and 
cyclophosphamide (high-risk patients) followed by allogeneic or syngeneic bone 
marrow transplantation.

II.  Compare the therapeutic effects of these cytoreduction regimens with 
those reported in the literature for similar patients who undergo syngeneic or 
allogeneic marrow transplantation following cytoreduction that includes 
total-body irradiation.

III.  Determine the early and late toxic effects produced by these 
chemotherapy regimens in this patient population.

Entry Criteria

Disease Characteristics:

The following hematologic malignancies are eligible:
 Acute nonlymphocytic leukemia in one of the following categories:
  In complete remission
  In early relapse
  Newly diagnosed FAB types M6 and M7

 Myelodysplastic syndromes including:
  Refractory anemia with excessive blasts
  Refractory anemia with excessive blasts in transformation
  Chronic myelomonocytic leukemia

 Secondary acute myeloid leukemia

Transplantation priority given in decreasing order of:
 First remission
 Second remission
 Third remission
 Early relapse, with priority further reduced for:
  Refractory response to platelet transfusion
  Severe infection within 6 weeks prior to referral
  History of major organ pathology or insult (hepatitis, renal damage,
   pulmonary disease, cystitis, etc.)

CNS disease allowed but priority status for transplantation lowered

Donor Criteria:
 Sibling or matched related/unrelated donor required
  Donor priority as follows:
   Monozygotic twin
   Genotypical or phenotypical HLA-A, -B, -C, and -D match
   Match at any 2 loci (A, B, Dr) on the other haplotype

  ABO-compatible donor preferred
   Marrow processed to eliminate mismatched erythrocytes if ABO incompatible

  In case of multiple donors, priority is:
   ABO compatibility
   Age over 18
   Same sex

  No physiologic, psychologic, or medical contraindication to donation
   procedure

  No increased anesthetic risk due to pre-existing illness

  HIV negative

Prior/Concurrent Therapy:

See Disease Characteristics

Patient Characteristics:

Age:
 6 months to 60 years

Performance status:
 No preterminal or moribund patients

Life expectancy:
 No severe limits on life expectancy due to diseases other than leukemia

Hematopoietic:
 See Disease Characteristics

Hepatic:
 Bilirubin no greater than 2.0 mg/dL
 Transaminases no greater than 3 times normal
 No severe hepatic disease

Renal:
 Creatinine no greater than 1.5 mg/dL OR
 Creatinine clearance at least 60 mL/min
 No severe renal disease
 No history of severe cystitis with cyclophosphamide

Cardiovascular:
 LVEF at least 50%
 No symptomatic cardiac disease

Pulmonary:
 FEV1 and FVC at least 75% of normal
 No severe pulmonary disease

Other:
 HIV negative
 No severe personality disorder or severe mental illness
 No condition (such as substance abuse) that would markedly increase the
  morbidity and mortality of transplantation

 Criteria of hepatic, renal, cardiac, and pulmonary function and mental
  illness are used only for initial screening of potential candidates;
  patients who do not meet these criteria may still be eligible at the
  discretion of the transplant team

Expected Enrollment

A total of 40 patients will be accrued for this study within 2.7 years.

Outline

Low-risk patients (those in first complete remission (CR) who achieved CR with 
1 course of chemotherapy) are treated on Regimen A.  High-risk patients (those 
in second or subsequent CR who required more than 1 course of chemotherapy to 
achieve first CR or those with myelodysplastic syndrome) are treated on 
Regimen B.
 
All patients undergo diagnostic lumbar puncture prior to beginning therapy and 
fluid is examined for CNS disease.  Patients receive methotrexate IT along 
with the tap.

Prior to initiation of chemotherapy, patients with CNS disease present on 
diagnostic lumbar puncture receive methotrexate IT every 2-3 days until lumbar 
puncture shows no leukemia cells and then 1 additional dose.  Cytoreductive 
chemotherapy begins 3 days after the last dose of methotrexate.

Regimen A:  Patients receive oral busulfan every 6 hours on days -7 to -4 for 
a total of 16 doses and cyclophosphamide IV over 2 hours on days -3 and -2.  
Allogeneic bone marrow is infused on day 0.

Regimen B:  Patients receive oral busulfan every 6 hours on days -9 to -6 for 
a total of 16 doses.  Patients receive cytarabine IV over 1 hour every 12 
hours on days -5 and -4 and cyclophosphamide IV over 2 hours on days -3 and 
-2.  Allogeneic bone marrow is infused on day 0.

Graft versus host disease prophylaxis:  Patients receive cyclosporine IV 
continuously on days -1 to 28 followed by a taper of oral cyclosporine until 
day 180.  Patients receive methotrexate IV on days 1, 3, 6, and 11.

CNS disease prophylaxis:  Patients receive 5 more doses of methotrexate IT 
weekly beginning between days 50 and 70.  In addition, patients with history 
of CNS disease receive 1 dose of methotrexate IT monthly for 1 year.

Patients are followed frequently during the first 100 days, at 6 months, 1 
year, and then annually thereafter.

Trial Contact Information

Trial Lead Organizations

Barbara Ann Karmanos Cancer Institute

Jared Klein, MD, Protocol chair(Contact information may not be current)		Ph: 313-745-8861; 800-527-6266 Email: kleinj@karmanos.org

Registry Information
Official Title		ALLOGENEIC AND SYNGENEIC MARROW TRANSPLANTATION IN PATIENTS WITH ACUTE NON-LYMPHOCYTIC LEUKEMIA
Trial Start Date		1987-08-06
Registered in ClinicalTrials.gov		NCT00002547
Date Submitted to PDQ		1987-08-06
Information Last Verified		2007-07-12

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