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

Fludarabine and Busulfan Followed by Allogeneic Stem Cell Transplant in Treating Older Patients With Acute Myeloid Leukemia in First Complete Remission
This study is currently recruiting participants.
Verified April 2011 by National Cancer Institute (NCI)

First Received on October 3, 2003.  
Last Updated on April 2, 2011  
History of Changes
Sponsor: Cancer and Leukemia Group B
Collaborator: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00070135
  Purpose

RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient’s immune system from rejecting the donor’s stem cells. The donated stem cells may replace the patient’s immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor’s T cells (donor lymphocyte infusion) after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body’s normal cells. Giving tacrolimus and methotrexate after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving fludarabine together with busulfan followed by a donor stem cell transplant works in treating older patients with acute myeloid leukemia that is in the first complete remission.

Condition Intervention Phase
Leukemia Biological: filgrastim
Biological: graft-versus-tumor induction therapy
Drug: busulfan
Drug: fludarabine phosphate
Drug: methotrexate
Drug: tacrolimus
Procedure: peripheral blood stem cell transplantation
Phase 2

Study Type: Interventional
Study Design: 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 National Cancer Institute (NCI):

Primary Outcome Measures:

  • Progression-free survival at 2 years [ Designated as safety issue: No ]

Estimated Enrollment: 61
Study Start Date: January 2004
Estimated Primary Completion Date: April 2005 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

  • Determine whether allogeneic stem cell transplantation from a matched sibling or unrelated donor using a nonmyeloablative preparative regimen comprising fludarabine and busulfan results in a 2-year disease-free survival that is better than historical results using standard chemotherapy in older patients with acute myeloid leukemia in first morphologic complete remission.

Secondary

  • Determine the 2-year actuarial risks of transplant-related mortality, acute and chronic graft-versus-host disease, and relapse in patients treated with this regimen.
  • Determine the recovery of T- and B-cell number and function and the time course of T, B, and myeloid progenitor chimerism in patients treated with this regimen.
  • Determine the pharmacokinetics of this regimen in these patients.

OUTLINE: This is a multicenter study.

  • 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.
  • Graft-versus-host disease (GVHD) prophylaxis: Patients receive oral or IV tacrolimus twice daily starting on days -2, with tapering 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 (Thymoglobulin) IV over 4-6 hours on days -4 through -2.
  • Allogeneic peripheral blood stem cell transplantation (PBSC): Patients undergo allogeneic PBSC transplantation on day 0. Patients then receive filgrastim (G-CSF) subcutaneously daily beginning on day 12 and continuing until blood counts recover. Patients with progressive disease will be removed from the study and may receive additional treatment at the discretion of the investigator.

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

PROJECTED ACCRUAL: A total of 61 patients will be accrued for this study.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Diagnosis of acute myeloid leukemia (AML) in first morphologic complete remission

    • No FAB M3 disease
    • Preceding myelodysplastic syndromes and treatment-related AML allowed
  • Morphologic complete remission achieved within the past 6 months and after no more than 2 courses of induction chemotherapy with standard cytotoxic chemotherapy (e.g., cytarabine and an anthracycline) or after no more than 4 courses of a hypomethylating agent-containing regimen including either 5-azacytidine or decitabine

    • Complete morphologic remission is defined by all of the following criteria:

      • Normal bone marrow morphology with less than 5% blasts
      • Absolute neutrophil count greater than 1,000/mm^3*
      • Platelet count greater than 100,000/mm^3*
      • No extramedullary leukemia
      • No blasts in peripheral blood NOTE: *Must be sustained for at least 30 days
  • No more than 2 courses of prior consolidation therapy

    • Any consolidation regimen that does not require transplantation allowed
  • No acute leukemia after blast transformation of prior chronic myelogenous leukemia or other myeloproliferative disease
  • Prior CNS involvement allowed provided the disease is in remission at time of transplantation
  • The following donors will be allowed:

    • Available HLA-identical (6/6) sibling donor by serological typing (A, B, DR)
    • Locus matched unrelated donor (10/10) by high resolution molecular typing (HLA-A, -B, -C, -DRB1, and -DQB1).
    • No syngeneic donors

PATIENT CHARACTERISTICS:

Age

  • 60 to 74

Performance status

  • 0-2

Life expectancy

  • Not specified

Hematopoietic

  • See Disease Characteristics

Hepatic

  • Bilirubin less than 2 mg/dL*

    • Bilirubin 2-3 mg/dL with normal direct bilirubin allowed
  • AST less than 3 times upper limit of normal* NOTE: *Unless attributable to disease

Renal

  • Creatinine clearance at least 40 mL/min (unless attributable to disease)

Cardiovascular

  • LVEF at least 30% by MUGA or ECHO

Pulmonary

  • DLCO greater than 40%
  • No symptomatic pulmonary disease

Other

  • Not pregnant
  • Fertile patients must use effective contraception
  • HIV negative
  • No uncontrolled diabetes mellitus
  • No active serious infection requiring antibiotics
  • No known hypersensitivity to E. coli-derived products

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • See Disease Characteristics

Chemotherapy

  • See Disease Characteristics
  • At least 4 weeks since prior chemotherapy

Endocrine therapy

  • Not specified

Radiotherapy

  • At least 4 weeks since prior radiotherapy

Surgery

  • At least 4 weeks since prior surgery
  Contacts and Locations

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

Locations
United States, California
UCSF Helen Diller Family Comprehensive Cancer Center Recruiting
San Francisco, California, United States, 94115
Contact: Clinical Trials Office – UCSF Helen Diller Family Comprehensi     877-827-3222        
United States, Delaware
Tunnell Cancer Center at Beebe Medical Center Recruiting
Lewes, Delaware, United States, 19958
Contact: Clinical Trials Office – Tunnell Cancer Center     302-645-3171        
CCOP – Christiana Care Health Services Recruiting
Newark, Delaware, United States, 19713
Contact: Clinical Trial Office – CCOP – Christiana Care Health Services     302-623-4450        
United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center Recruiting
Baltimore, Maryland, United States, 21201
Contact: Clinical Trials Office – Greenebaum Cancer Center at Universit     800-888-8823        
Union Hospital of Cecil County Recruiting
Elkton MD, Maryland, United States, 21921
Contact: Frank Beardell, MD     302-737-7700        
United States, Massachusetts
Beth Israel Deaconess Medical Center Recruiting
Boston, Massachusetts, United States, 02215
Contact: Clinical Trials Office – Beth Israel Deaconess Medical Center     617-667-9925        
Dana-Farber/Brigham and Women’s Cancer Center Recruiting
Boston, Massachusetts, United States, 02115
Contact: Clinical Trials Office     617-724-5200        
Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02115
Contact: Edwin P. Alyea, MD     617-632-3465        
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Clinical Trials Office – Massachusetts General Hospital     877-726-5130        
United States, Minnesota
Masonic Cancer Center at University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Clinical Trials Office – Masonic Cancer Center at University o     612-624-2620        
United States, Missouri
Siteman Cancer Center at Barnes-Jewish Hospital – Saint Louis Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Ravi Vij, MD     314-454-8323        
United States, New Jersey
Cancer Institute of New Jersey at Cooper – Voorhees Recruiting
Voorhees, New Jersey, United States, 08043
Contact: Clinical Trials Office – Cancer Institute of New Jersey at Coo     856-325-6757        
United States, New York
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263-0001
Contact: Clinical Trials Office – Roswell Park Cancer Institute     877-275-7724        
Monter Cancer Center of the North Shore-LIJ Health System Recruiting
Lake Success, New York, United States, 11042
Contact: Ruthee-Lu Bayer, MD     516-562-8973        
Don Monti Comprehensive Cancer Center at North Shore University Hospital Recruiting
Manhasset, New York, United States, 11030
Contact: Clinical Trials Office – Don Monti Comprehensive Cancer Center     516-734-8900        
CCOP – North Shore University Hospital Recruiting
Manhasset, New York, United States, 11030
Contact: Ruthee-Lu Bayer, MD     516-562-8973        
Long Island Jewish Medical Center Recruiting
New Hyde Park, New York, United States, 11040
Contact: Ruthee-Lu Bayer, MD     516-562-8973        
New York Weill Cornell Cancer Center at Cornell University Recruiting
New York, New York, United States, 10021
Contact: Clinical Trials Office – New York Weill Cornell Cancer Center     212-746-1848        
United States, North Carolina
Wake Forest University Comprehensive Cancer Center Recruiting
Winston-Salem, North Carolina, United States, 27157-1096
Contact: Clinical Trials Office – Wake Forest University Comprehensive     336-713-6771        
United States, Ohio
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center Recruiting
Columbus, Ohio, United States, 43210-1240
Contact: Ohio State University Cancer Clinical Trial Matching Service     866-627-7616     osu@emergingmed.com    
Sponsors and Collaborators
Cancer and Leukemia Group B
Investigators
Study Chair: Steven M. Devine, MD Ohio State University Comprehensive Cancer Center
  More Information

Additional Information:

No publications provided

Responsible Party: Monica M. Bertagnolli, Cancer and Leukemia Group B
ClinicalTrials.gov Identifier: NCT00070135    
History of Changes
Other Study ID Numbers: CDR0000330001, CALGB-100103
Study First Received: October 3, 2003
Last Updated: April 2, 2011
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):

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, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Busulfan
Methotrexate
Fludarabine monophosphate
Tacrolimus
Fludarabine
Lenograstim
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on August 21, 2012

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