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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00070135
First received: October 3, 2003
Last updated: July 27, 2015
Last verified: July 2015
  Purpose

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.


Condition Intervention Phase
Adult Acute Myeloid Leukemia in Remission
Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Biological: filgrastim
Biological: Anti-Thymocyte Globulin
Drug: busulfan
Drug: fludarabine phosphate
Drug: methotrexate
Drug: tacrolimus
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study Of Allogeneic Transplant For Older Patients With AML In First Morphologic Complete Remission Using A Non-Myeloablative Preparative Regimen

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • DFS [ Time Frame: up to 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • DFS profiles of the two combined populations [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Transplant related mortality (TRM) defined as death after transplant not secondary to relapse [ Time Frame: Within the first 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 61
Study Start Date: January 2004
Estimated Primary Completion Date: December 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.

Biological: filgrastim
Given SC
Biological: Anti-Thymocyte Globulin
Given IV
Drug: busulfan
Given IV
Drug: fludarabine phosphate
Given IV
Drug: methotrexate
Given IV
Drug: tacrolimus
Given PO or IV
Procedure: Allogeneic Hematopoietic Stem Cell Transplantation
Undergo allogeneic PBSC transplantation
Other Name: HSC, HSCT

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.

  Eligibility

Ages Eligible for Study:   60 Years to 74 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Eligibility Criteria:

  • Patients with acute myeloid leukemia (AML) (excluding French-American-British [FAB] classification system M3) who have achieved a first morphologic complete remission and who meet the criteria below; patients with preceding myelodysplastic syndrome (MDS) or treatment-related AML are eligible; patients with prior central nervous system (CNS) involvement are eligible as long as disease is in remission at transplant; patients with acute leukemia following blast transformation of prior chronic myeloid leukemia (CML) or other myeloproliferative disease are excluded
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00070135

Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Delaware
Tunnell Cancer Center at Beebe Medical Center
Lewes, Delaware, United States, 19958
CCOP - Christiana Care Health Services
Newark, Delaware, United States, 19713
United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
Union Hospital of Cecil County
Elkton MD, Maryland, United States, 21921
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Dana-Farber/Brigham and Women's Cancer Center
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, Minnesota
Masonic Cancer Center at University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
Saint Louis, Missouri, United States, 63110
United States, New Jersey
Cancer Institute of New Jersey at Cooper - Voorhees
Voorhees, New Jersey, United States, 08043
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Monter Cancer Center of the North Shore-LIJ Health System
Lake Success, New York, United States, 11042
CCOP - North Shore University Hospital
Manhasset, New York, United States, 11030
Don Monti Comprehensive Cancer Center at North Shore University Hospital
Manhasset, New York, United States, 11030
Long Island Jewish Medical Center
New Hyde Park, New York, United States, 11040
Mount Sinai Medical Center
New York, New York, United States, 10029
New York Weill Cornell Cancer Center at Cornell University
New York, New York, United States, 10021
United States, North Carolina
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
United States, Ohio
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210-1240
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Investigators
Study Chair: Steven M. Devine, MD Ohio State University Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00070135     History of Changes
Other Study ID Numbers: CALGB-100103, CDR0000330001, NCI-2009-00438, U10CA180821
Study First Received: October 3, 2003
Last Updated: July 27, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Alliance for Clinical Trials in Oncology:
adult acute myeloid leukemia in remission
secondary acute myeloid leukemia
adult acute monocytic leukemia (M5b)
adult acute erythroid leukemia (M6)
adult acute megakaryoblastic leukemia (M7)
adult acute minimally differentiated myeloid leukemia (M0)
adult acute myeloblastic leukemia with maturation (M2)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myelomonocytic leukemia (M4)
adult acute monoblastic leukemia (M5a)
adult acute myeloid leukemia with t(8;21)(q22;q22)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with 11q23 (MLL) abnormalities

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Neoplasms
Neoplasms by Histologic Type
Precancerous Conditions
Antilymphocyte Serum
Busulfan
Fludarabine
Fludarabine phosphate
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists

ClinicalTrials.gov processed this record on July 30, 2015