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

This study is ongoing, but not recruiting participants.

Sponsored by: Barbara Ann Karmanos Cancer Institute
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00002547
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with bone marrow transplantation may allow the doctor to give higher doses of chemotherapy and kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of bone marrow transplantation following combination chemotherapy in treating patients with acute myeloid leukemia or myelodysplastic syndrome .


Condition Intervention Phase
Leukemia
Myelodysplastic Syndromes
Drug: busulfan
Drug: cyclophosphamide
Drug: cyclosporine
Drug: cytarabine
Drug: methotrexate
Procedure: allogeneic bone marrow transplantation
Procedure: syngeneic bone marrow transplantation
Phase II

MedlinePlus related topics:   Bone Marrow Transplantation    Cancer    Leukemia, Adult Acute    Leukemia, Adult Chronic    Leukemia, Childhood   

ChemIDplus related topics:   Cyclophosphamide    Cytarabine    Cytarabine hydrochloride    Methotrexate    Cyclosporine    Cyclosporin    Busulfan   

U.S. FDA Resources

Study Type:   Interventional
Study Design:   Treatment
Official Title:   ALLOGENEIC AND SYNGENEIC MARROW TRANSPLANTATION IN PATIENTS WITH ACUTE NON-LYMPHOCYTIC LEUKEMIA

Further study details as provided by National Cancer Institute (NCI):

Estimated Enrollment:   40
Study Start Date:   August 1987

Detailed Description:

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.

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.

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

  Eligibility
Ages Eligible for Study:   up to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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

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

PRIOR CONCURRENT THERAPY: See Disease Characteristics

  Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00002547

Locations
United States, Michigan
Barbara Ann Karmanos Cancer Institute    
      Detroit, Michigan, United States, 48201

Sponsors and Collaborators
Barbara Ann Karmanos Cancer Institute

Investigators
Study Chair:     Jared L. Klein, MD     Barbara Ann Karmanos Cancer Institute    
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site
 

Study ID Numbers:   CDR0000063305, WSU-D-696-87, NCI-V93-0345
First Received:   November 1, 1999
Last Updated:   July 23, 2008
ClinicalTrials.gov Identifier:   NCT00002547
Health Authority:   United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent childhood acute myeloid leukemia  
recurrent adult acute myeloid leukemia  
untreated adult acute myeloid leukemia  
untreated childhood acute myeloid leukemia and other myeloid malignancies  
adult acute myeloid leukemia in remission  
childhood acute myeloid leukemia in remission  
adult acute erythroid leukemia (M6)  
adult acute myeloblastic leukemia without maturation (M1)  
adult acute myeloblastic leukemia with maturation (M2)  
adult acute promyelocytic leukemia (M3)  
adult acute myelomonocytic leukemia (M4)  
adult acute monoblastic leukemia (M5a)  
adult acute megakaryoblastic leukemia (M7)  
childhood acute myeloblastic leukemia without maturation (M1)  
childhood acute myeloblastic leukemia with maturation (M2)
childhood acute promyelocytic leukemia (M3)
childhood acute myelomonocytic leukemia (M4)
childhood acute monoblastic leukemia (M5a)
childhood acute monocytic leukemia (M5b)
childhood acute erythroleukemia (M6)
childhood acute megakaryocytic leukemia (M7)
refractory anemia with excess blasts
refractory anemia with excess blasts in transformation
chronic myelomonocytic leukemia
secondary acute myeloid leukemia
adult acute monocytic leukemia (M5b)
previously treated myelodysplastic syndromes
childhood myelodysplastic syndromes

Study placed in the following topic categories:
Leukemia, Monocytic, Acute
Cyclosporine
Precancerous Conditions
Clotrimazole
Chronic myelomonocytic leukemia
Refractory anemia
Miconazole
Acute myelomonocytic leukemia
Cyclophosphamide
Di Guglielmo's syndrome
Leukemia, Myeloid, Acute
Cyclosporins
Leukemia
Preleukemia
Anemia, Refractory
Leukemia, Promyelocytic, Acute
Neoplasm Metastasis
Methotrexate
Acute erythroblastic leukemia
Acute myeloid leukemia, adult
Acute myelocytic leukemia
Cytarabine
Myelodysplastic syndromes
Hematologic Diseases
Leukemia, Myelomonocytic, Chronic
Myelodysplastic Syndromes
Myelodysplasia
Tioconazole
Myeloproliferative Disorders
Anemia

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Reproductive Control Agents
Pathologic Processes
Therapeutic Uses
Syndrome
Antifungal Agents
Abortifacient Agents
Alkylating Agents
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors
Disease
Neoplasms by Histologic Type
Enzyme Inhibitors
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Immunosuppressive Agents
Antiviral Agents
Pharmacologic Actions
Neoplasms
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents

ClinicalTrials.gov processed this record on August 27, 2008




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