Chemotherapy Plus Peripheral Stem Cell Transplantation in Treating Patients With Acute Myeloid Leukemia in Second Remission

NCT ID: NCT00002768

Last Updated: 2016-06-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1996-06-30
• Study Completion Date: 2009-03-31

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 peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of peripheral stem cell transplantation following chemotherapy in treating patients with acute myeloid leukemia in second remission.

Detailed Description

OBJECTIVES: I. Determine the ability of mobilization using cytarabine, etoposide, and filgrastim (G-CSF), conditioning using busulfan and etoposide, and autologous peripheral blood stem cell transplantation to generate a 2-year disease-free survival rate in at least 30% of patients with acute myeloid leukemia (AML) in second complete remission. II. Determine whether the treatment-related mortality can be limited to less than 20% in patients treated with this regimen. III. Determine whether adequate numbers of PBSC can be collected in these patients. IV. Determine the engraftment kinetics of primed PBSC obtained from these patients.

OUTLINE: Mobilization/harvest: Patients receive cytarabine IV over 2 hours every 12 hours and etoposide IV continuously on days 1-4. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning on day 14 and continuing until peripheral blood stem cells (PBSC) are harvested. When blood counts recover, PBSC are harvested and selected for CD34+ cells. Conditioning: Beginning at least 4 weeks after hospital discharge for mobilization and harvest and when blood counts recover, patients receive oral busulfan every 6 hours on days -7 to -4 and etoposide IV over 4 hours on day -3. PBSC are reinfused on day 0. G-CSF is administered SC beginning on day 0 and continuing until blood counts recover. Patients with documented CNS disease at first relapse receive methotrexate intrathecally at intervals of 1 week or greater before and/or after PBSC transplantation for a total of 6 doses. Patients are followed every 3 months for 2 years and then every 6 months for 3 years.

PROJECTED ACCRUAL: A total of 26-48 patients will be accrued within 2 years.

Conditions

Leukemia

Study Design

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

Study Groups

Autologous stem cell transplantation

Patients receive consolidation chemotherapy followed by autologous stem cell transplantation

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: BIOLOGICAL

10 microgram/kg body wt subcutaneously daily beginning on d 14 and con't until peripheral blood collection is completed

busulfan

Intervention Type: DRUG

1 mg/kg PO q 6 hrs for 16 doses on days -7 thru -4.

cytarabine

Intervention Type: DRUG

2000 mg/ sq meter IV over 2 hours q 12 hrs x 8 doses on days 1-4

etoposide

Intervention Type: DRUG

40 mg/kg (total dose) IV cont infusion over 96 hrs on days 1-4 of consolidation therapy and 60 mg/kg IV over 4 hrs on day -3 of transplant

methotrexate

Intervention Type: DRUG

For patients with documented CNS disease at first relapse, 12 mg intrathecal for a total of 6 doses given before and/or after transplantation

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Infusion on Day 0

Interventions

filgrastim

10 microgram/kg body wt subcutaneously daily beginning on d 14 and con't until peripheral blood collection is completed

Intervention Type: BIOLOGICAL

busulfan

1 mg/kg PO q 6 hrs for 16 doses on days -7 thru -4.

Intervention Type: DRUG

cytarabine

2000 mg/ sq meter IV over 2 hours q 12 hrs x 8 doses on days 1-4

Intervention Type: DRUG

etoposide

40 mg/kg (total dose) IV cont infusion over 96 hrs on days 1-4 of consolidation therapy and 60 mg/kg IV over 4 hrs on day -3 of transplant

Intervention Type: DRUG

methotrexate

For patients with documented CNS disease at first relapse, 12 mg intrathecal for a total of 6 doses given before and/or after transplantation

Intervention Type: DRUG

peripheral blood stem cell transplantation

Infusion on Day 0

Intervention Type: PROCEDURE

Other Intervention Names

G-CSF; Ara-C

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS: Diagnosis of acute myeloid leukemia (AML) in second complete remission (CR) for 30 days to less than 1 year before study entry Second CR defined by the following: Neutrophil count at least 1,000/mm3 Platelet count at least 100,000/mm3 Normal bone marrow morphology with no excess blasts (greater than 5%) No myelodysplasia No extramedullary or CNS leukemia Initial diagnosis of de novo AML (M0-M7) No prior myelodysplasia No myeloproliferative disease No secondary AML Cytogenetics not required No cytogenetic evidence of persistent leukemia if cytogenetics performed

PATIENT CHARACTERISTICS: Age: 15 to 69 Hematopoietic: See Disease Characteristics Granulocyte count at least 1,000/mm3 Hepatic: Bilirubin less than 1.5 mg/dL AST less than 3 times normal Alkaline phosphatase less than 3 times normal No cirrhosis or chronic hepatitis Biopsy required if chronic liver disease suspected (history of alcohol abuse or possible hepatitis) Renal: Creatinine less than 2.0 mg/dL Other: Not pregnant or nursing Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior bone marrow/stem cell transplantation Chemotherapy: Prior non-ablative chemotherapy at initial diagnosis, during initial remission, or as reinduction therapy (to produce current second remission) allowed At least 4 weeks since hospital discharge after reinduction therapy Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified Other: No prior post-remission therapy for second remission

• Minimum Eligible Age: 15 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Alliance for Clinical Trials in Oncology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Charles Linker, MD

Role: STUDY_CHAIR

University of California, San Francisco

Locations

UCSF Cancer Center and Cancer Research Institute

San Francisco, California, United States

Marlene & Stewart Greenebaum Cancer Center, University of Maryland

Baltimore, Maryland, United States

St. Joseph's Hospital and Medical Center

Paterson, New Jersey, United States

Countries

United States

References

Linker CA, Owzar K, Powell B, Hurd D, Damon LE, Archer LE, Larson RA; Cancer and Leukemia Group B. Auto-SCT for AML in second remission: CALGB study 9620. Bone Marrow Transplant. 2009 Sep;44(6):353-9. doi: 10.1038/bmt.2009.36. Epub 2009 Mar 16.

Reference Type: RESULT

PMID: 19289999 (View on PubMed)

Other Identifiers

U10CA031946

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CLB-9620

Identifier Type: -

Identifier Source: secondary_id

CDR0000064734

Identifier Type: REGISTRY

Identifier Source: secondary_id

CALGB-9620

Identifier Type: -

Identifier Source: org_study_id