Fludarabine and Busulfan Followed by Allogeneic Stem Cell Transplant in Treating Older Patients With Acute Myeloid Leukemia in First Complete Remission

NCT ID: NCT00070135

Last Updated: 2018-06-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 121 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-01-31
• Study Completion Date: 2016-06-15

Brief Summary

This phase II trial studies how well fludarabine and busulfan followed by a donor (allogeneic) stem cell transplant work in treating older patients with acute myeloid leukemia that is in first complete remission. Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor peripheral blood stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. It may also stops the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Giving tacrolimus, methotrexate, and rabbit antithymocyte globulin before or after the transplant may stop this from happening.

Detailed Description

PRIMARY OBJECTIVES:

I. Determine if allogeneic transplantation from a matched sibling or unrelated donor using a non-myeloablative preparative regimen results in a 2-year disease-free survival (DFS) that is better than historical results using standard chemotherapy.

SECONDARY OBJECTIVES:

I. Determine 2-year actuarial risks of transplant-related mortality, acute and chronic graft-versus-host (GVHD) disease and relapse among patients with acute myeloid leukemia (AML) in first complete remission (CR1) following a non-myeloablative preparative regimen.

II. To examine recovery of T and B cell number and function following non-myeloablative stem cell transplant.

III. To examine the time course of T, B and myeloid progenitor chimerism following this preparative regimen.

IV. To characterize the pharmacokinetics of intravenous busulfan used in a non-myeloablative preparation regimen in AML patients age >= 60 years.

OUTLINE:

PREPARATIVE REGIMEN: Patients receive fludarabine intravenously (IV) over 30 minutes on days -7 to -3 and busulfan IV over 2 hours 4 times per day (every 6 hours) on days -4 and -3.

GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive tacrolimus orally (PO) or IV twice daily (BID) on days -2 with taper between days 90-120, and stopping by days 150-180. Patients also receive methotrexate IV on days 1, 3, 6, and 11 and rabbit antithymocyte globulin IV over 4-6 hours on days -4 through -2.

ALLOGENEIC PERIPHERAL BLOOD STEM CELL TRASNPLANTATION (PBSC): Patients undergo allogeneic PBSC transplant on day 0. Patients then receive filgrastim subcutaneously (SC) daily beginning on day 12 and continuing until blood counts recover.

Patients are followed monthly for 1 year, every 3 months for 1 year, and then every 6 months for 3 years.

Conditions

Adult Acute Myeloid Leukemia in Remission; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome

Study Design

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

Study Groups

Treatment (fludarabine, busulfan, allogeneic PBSC)

PREPARATIVE REGIMEN: Patients receive fludarabine IV over 30 minutes on days -7 to -3 and busulfan IV over 2 hours 4 times per day (every 6 hours) on days -4 and -3.

GVHD PROPHYLAXIS: Patients receive tacrolimus PO or IV BID on days -2 with taper between days 90-120, and stopping by days 150-180. Patients also receive methotrexate IV on days 1, 3, 6, and 11 and rabbit antithymocyte globulin IV over 4-6 hours on days -4 through -2.

ALLOGENEIC PBSC: Patients undergo allogeneic PBSC transplant on day 0. Patients then receive filgrastim SC daily beginning on day 12 and continuing until blood counts recover.

Group Type: EXPERIMENTAL

filgrastim

Intervention Type: BIOLOGICAL

Given SC

Anti-Thymocyte Globulin

Intervention Type: BIOLOGICAL

Given IV

busulfan

Intervention Type: DRUG

Given IV

fludarabine phosphate

Intervention Type: DRUG

Given IV

methotrexate

Intervention Type: DRUG

Given IV

tacrolimus

Intervention Type: DRUG

Given PO or IV

Allogeneic Hematopoietic Stem Cell Transplantation

Intervention Type: PROCEDURE

Undergo allogeneic PBSC transplantation

Interventions

filgrastim

Given SC

Intervention Type: BIOLOGICAL

Anti-Thymocyte Globulin

Given IV

Intervention Type: BIOLOGICAL

busulfan

Given IV

Intervention Type: DRUG

fludarabine phosphate

Given IV

Intervention Type: DRUG

methotrexate

Given IV

Intervention Type: DRUG

tacrolimus

Given PO or IV

Intervention Type: DRUG

Allogeneic Hematopoietic Stem Cell Transplantation

Undergo allogeneic PBSC transplantation

Intervention Type: PROCEDURE

Other Intervention Names

HSC, HSCT

Eligibility Criteria

Inclusion Criteria

• Complete remission (CR) will be defined according to the revised recommendations of the International Working Group (24) as all of the following:

• Normal bone marrow morphology with < 5% blasts
• Absolute neutrophil count (ANC) > 1,000/uL, referring to the count needed to confirm that the patient achieved a CR
• Platelet count > 100,000/uL
• No extramedullary leukemia
• No blasts in peripheral blood
• CR was achieved after one or two (but no more than two) cycles of induction chemotherapy with standard cytotoxic chemotherapy (e.g., cytarabine and an anthracycline) or after no more than four cycles of a hypomethylating agent containing regimen including either 5-azacytidine or decitabine
• Patients may have received as many as but no more than two cycles of consolidation therapy prior to transplant; any consolidation regimen that does not require transplant can be used; no more than 6 months can elapse from documentation of morphologic CR to transplant; the platelet count does not need to be > 100,000/uL after consolidation, as long as the bone marrow assessment prior to transplant does not show relapse
• Identification of hematopoietic cell donor
• >= 4 weeks since prior chemotherapy, radiation therapy, and surgery
• Performance status 0-2
• Diffusion capacity of carbon monoxide (DLCO) > 40% with no symptomatic pulmonary disease
• Left ventricular ejection fraction (LVEF) by multi gated acquisition scan (MUGA) or echocardiogram (ECHO) >= 30%
• No uncontrolled diabetes mellitus or active serious infection requiring antibiotics
• No known hypersensitivity to E. coli-derived products
• No human immunodeficiency virus (HIV) infection
• Calculated creatinine clearance >= 40 cc/min
• Bilirubin < 2 mg/dL

• If bilirubin is 2-3 mg/dL, but direct bilirubin is normal then patient will be considered eligible
• Aspartate aminotransferase (AST) < 3 x upper limit of normal
• DONOR: HLA-identical sibling (6/6); the donor must be determined to be an human leukocyte antigen (HLA)-identical sibling (6/6) by serologic typing for class (A, B) and low resolution molecular typing for class II (DRB1)
• DONOR: Matched unrelated donor (10/10); high resolution molecular typing at the following loci is required: HLA-A, -B, -C, -DRB1, and -DQB1
• DONOR: the donor must be healthy and must be an acceptable donor as per institutional standards for stem cell donation
• DONOR: the donor must have no significant cardiopulmonary, renal, endocrine, or hepatic disease
• DONOR: there is no donor age restriction if the donor is a matched sibling
• DONOR: syngeneic donors are not eligible

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 74 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

Steven M. Devine, MD

Role: STUDY_CHAIR

Ohio State University Comprehensive Cancer Center

Locations

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, United States

Tunnell Cancer Center at Beebe Medical Center

Lewes, Delaware, United States

CCOP - Christiana Care Health Services

Newark, Delaware, United States

Greenebaum Cancer Center at University of Maryland Medical Center

Baltimore, Maryland, United States

Union Hospital of Cecil County

Elkton, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana-Farber/Brigham and Women's Cancer Center

Boston, Massachusetts, United States

Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, United States

Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis

St Louis, Missouri, United States

Cancer Institute of New Jersey at Cooper - Voorhees

Voorhees Township, New Jersey, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Monter Cancer Center of the North Shore-LIJ Health System

Lake Success, New York, United States

CCOP - North Shore University Hospital

Manhasset, New York, United States

Don Monti Comprehensive Cancer Center at North Shore University Hospital

Manhasset, New York, United States

Long Island Jewish Medical Center

New Hyde Park, New York, United States

New York Weill Cornell Cancer Center at Cornell University

New York, New York, United States

Mount Sinai Medical Center

New York, New York, United States

Wake Forest University Comprehensive Cancer Center

Winston-Salem, North Carolina, United States

Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Countries

United States

References

Devine SM, Owzar K, Blum W, Mulkey F, Stone RM, Hsu JW, Champlin RE, Chen YB, Vij R, Slack J, Soiffer RJ, Larson RA, Shea TC, Hars V, Sibley AB, Giralt S, Carter S, Horowitz MM, Linker C, Alyea EP. Phase II Study of Allogeneic Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission Using a Reduced-Intensity Conditioning Regimen: Results From Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502. J Clin Oncol. 2015 Dec 10;33(35):4167-75. doi: 10.1200/JCO.2015.62.7273. Epub 2015 Nov 2.

Reference Type: DERIVED

PMID: 26527780 (View on PubMed)

Other Identifiers

CDR0000330001

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2009-00438

Identifier Type: REGISTRY

Identifier Source: secondary_id

U10CA180821

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CALGB-100103

Identifier Type: -

Identifier Source: org_study_id