A Phase II Study Of Allogeneic Transplant For Older Patients With AML In First Morphologic Complete Remission Using A Non-Myeloablative Preparative Regimen
60 Years
74 Years
Both
Leukemia
Trial Information
A Phase II Study Of Allogeneic Transplant For Older Patients With AML In First Morphologic Complete Remission Using A Non-Myeloablative Preparative Regimen
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Progression-free survival at 2 years
Safety Issue:
No
Principal Investigator
Steven M. Devine, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Ohio State University Comprehensive Cancer Center
Authority:
United States: Federal Government
Study ID:
CDR0000330001
NCT ID:
NCT00070135
Start Date:
January 2004
Completion Date:
Related Keywords:
- Leukemia
- 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
- Leukemia
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
| CCOP - Christiana Care Health Services | Wilmington, Delaware 19899 |
| CCOP - North Shore University Hospital | Manhasset, New York 11030 |
| Beth Israel Deaconess Medical Center | Boston, Massachusetts 02215 |
| Long Island Jewish Medical Center | New Hyde Park, New York 11040 |
| Mount Sinai Medical Center | New York, New York 10029 |
| Wake Forest University Comprehensive Cancer Center | Winston-Salem, North Carolina 27157-1096 |
| Greenebaum Cancer Center at University of Maryland Medical Center | Baltimore, Maryland 21201 |
| New York Weill Cornell Cancer Center at Cornell University | New York, New York 10021 |
| UCSF Helen Diller Family Comprehensive Cancer Center | San Francisco, California 94115 |
| Dana-Farber/Harvard Cancer Center at Dana-Farber Cancer Institute | Boston, Massachusetts 02115 |
| Masonic Cancer Center at University of Minnesota | Minneapolis, Minnesota 55455 |
| Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis | St. Louis, Missouri 63110 |
| Don Monti Comprehensive Cancer Center at North Shore University Hospital | Manhasset, New York 11030 |
| Cancer Institute of New Jersey at Cooper - Voorhees | Voorhees, New Jersey 08043 |
| Massachusetts General Hospital | Boston, Massachusetts 02114-2617 |
| Tunnell Cancer Center at Beebe Medical Center | Lewes, Delaware 19958 |
| Monter Cancer Center of the North Shore-LIJ Health System | Lake Success, New York 11042 |
| Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center | Columbus, Ohio 43210-1240 |
| Union Hospital of Cecil County | Elkton MD, Maryland 21921 |
| Dana-Farber/Brigham and Women's Cancer Center | Boston, Massachusetts 02115 |
