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

NCT ID: NCT00002547

Last Updated: 2012-08-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 280 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1987-08-31
• Study Completion Date: 2003-10-31

Brief Summary

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 .

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.

Conditions

Leukemia; Myelodysplastic Syndromes

Keywords

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 Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

busulfan

Intervention Type: DRUG

cyclophosphamide

Intervention Type: DRUG

cyclosporine

Intervention Type: DRUG

cytarabine

Intervention Type: DRUG

methotrexate

Intervention Type: DRUG

allogeneic bone marrow transplantation

Intervention Type: PROCEDURE

syngeneic bone marrow transplantation

Intervention Type: PROCEDURE

Other Intervention Names

Busulfex®; Myleran®; Cytoxan®; Neosar®; Gengraf; Neoral; Sandimmune; Sangcya; DepoCytTM; Liposomal Ara-C; Rheumatrex®; TrexallTM; Amethopterin; Methotrexate Sodium; MTX

Eligibility Criteria

Inclusion Criteria

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

• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Barbara Ann Karmanos Cancer Institute

OTHER

Sponsor Role: lead

Principal Investigators

Esteban Abella, MD

Role: PRINCIPAL_INVESTIGATOR

Barbara Ann Karmanos Cancer Institute

Locations

Barbara Ann Karmanos Cancer Institute

Detroit, Michigan, United States

Countries

United States

Other Identifiers

P30CA022453

Identifier Type: NIH

Identifier Source: secondary_id

View Link

WSU-D-696-87

Identifier Type: -

Identifier Source: secondary_id

NCI-V93-0345

Identifier Type: -

Identifier Source: secondary_id

CDR0000063305

Identifier Type: -

Identifier Source: org_study_id