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

Sponsors and Collaborators:	Cancer and Leukemia Group B 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 II

Study Type:	Interventional
Study Design:	Treatment, Open Label
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:

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Busulfan Methotrexate Fludarabine Fludarabine monophosphate Tacrolimus anhydrous Tacrolimus Filgrastim

U.S. FDA Resources

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
- 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 1,500/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
San Francisco, California, United States, 94115
United States, Delaware
CCOP - Christiana Care Health Services
Newark, Delaware, United States, 19713
Tunnell Cancer Center at Beebe Medical Center
Lewes, Delaware, United States, 19958
United States, Georgia
Blood and Marrow Transplant Group of Georgia
Atlanta, Georgia, United States, 30342
United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
Union Hospital Cancer Program at Union Hospital
Elkton MD, Maryland, United States, 21921
United States, Massachusetts
Dana-Farber/Brigham and Women's Cancer Center
Boston, Massachusetts, United States, 02115
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
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
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, 11042
Monter Cancer Center of the North Shore-LIJ Health System
Lake Success, New York, United States, 11042
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
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 Solove Research Institute at Ohio State University Medical Center
Columbus, Ohio, United States, 43210-1240
United States, Pennsylvania
Fox Chase Cancer Center - Philadelphia
Philadelphia, Pennsylvania, United States, 19111-2497
Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, United States, 15224-1791

Sponsors and Collaborators

Cancer and Leukemia Group B

National Cancer Institute (NCI)

Investigators

Study Chair:

Steven M. Devine, MD

Arthur G. James Cancer Hospital & Richard J. Solove Research Institute

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Cancer and Leukemia Group B ( Richard L. Schilsky )
Study ID Numbers:	CDR0000330001, CALGB-100103
Study First Received:	October 3, 2003
Last Updated:	April 14, 2009
ClinicalTrials.gov Identifier:	NCT00070135 History of Changes
Health Authority:	United States: Federal Government

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

Study placed in the following topic categories:

Leukemia, Monocytic, Acute
Antimetabolites
Immunologic Factors
Acute Myelomonocytic Leukemia
Folate
Acute Monoblastic Leukemia
Tacrolimus
Leukemia, Myeloid, Acute
Vitamin B9
Leukemia
Acute Erythroblastic Leukemia
Acute Myelocytic Leukemia
Acute Myeloid Leukemia, Adult
Neoplasm Metastasis
Methotrexate

Congenital Abnormalities
Alkylating Agents
Leukemia, Myeloid
Fludarabine monophosphate
Folinic Acid
Folic Acid Antagonists
Immunosuppressive Agents
Leukemia, Myelomonocytic, Acute
Folic Acid
Leukemia, Erythroblastic, Acute
Busulfan
Fludarabine
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Di Guglielmo's Syndrome

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Tacrolimus
Reproductive Control Agents
Leukemia, Myeloid, Acute
Leukemia
Therapeutic Uses
Abortifacient Agents
Methotrexate
Dermatologic Agents
Alkylating Agents

Nucleic Acid Synthesis Inhibitors
Neoplasms by Histologic Type
Enzyme Inhibitors
Fludarabine monophosphate
Leukemia, Myeloid
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Busulfan
Myeloablative Agonists
Fludarabine
Antineoplastic Agents, Alkylating
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 03, 2009