Treosulfan and Fludarabine in Treating Younger Patients Who Are Undergoing a Donor Stem Cell Transplant for Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

NCT ID: NCT00253513

Last Updated: 2012-06-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-06-30
• Study Completion Date: 2009-10-31

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as treosulfan and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving treosulfan and fludarabine together with a donor bone marrow transplant or a peripheral stem cell transplant may be an effective treatment for acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome.

PURPOSE: This phase II trial is studying giving treosulfan together with fludarabine to see how well it works in treating patients who are undergoing a donor stem cell transplant for acute myeloid leukemia, acute lymphoblastic leukemia, or myelodysplastic syndrome.

Detailed Description

OBJECTIVES:

Primary Phase

• Determine the best dose of treosulfan when administered with fludarabine as a reduced-intensity conditioning regimen followed by allogeneic hematopoietic stem cell transplantation, in terms of incidence of severe to fatal toxicity to major organ systems and incidence of graft failure, in patients with acute myeloid leukemia, lymphoblastic leukemia, or myelodysplastic syndrome.

Secondary Phase

• Determine the safety of this regimen, in terms of incidence of grade II-IV acute and chronic graft-versus-host disease, in these patients.
• Determine, preliminarily, the efficacy of this regimen, in terms of incidence of relapse, overall and disease-free survival, donor chimerism on days 28 and 100, and incidence of 200-day and 1-year nonrelapse mortality, in these patients.
• Determine the pharmacokinetic and pharmacodynamic profile of treosulfan in patients treated with this regimen.

OUTLINE: This is a multicenter, dose-finding study of treosulfan.

• Reduced-intensity conditioning: Patients receive treosulfan IV over 2 hours on days -6 to -4 and fludarabine IV over 30 minutes on days -6 to -2.

Cohorts of 5-10 patients receive escalating/de-escalating doses of treosulfan until the best dose is determined among the 3 pre-selected doses. The best dose is defined as the dose preceding that at which 4 of 10 patients experience dose-limiting toxicity.

• Allogeneic hematopoietic cell transplantation (AHCT): Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0.

All male patients with acute lymphoblastic leukemia OR male patients with acute myeloid leukemia who have prior or current testicular involvement receive external-beam radiotherapy to the testicles before AHCT.

After completion of study treatment, patents are followed periodically.

PROJECTED ACCRUAL: A total of 60 patients will be accrued for this study.

Conditions

Leukemia; Myelodysplastic Syndromes

Study Design

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

Interventions

fludarabine

30 mg/m2, IV for 5 days

Intervention Type: DRUG

treosulfan

12 or 14 g/m2, IV for 5 days

Intervention Type: DRUG

allogeneic blood or bone marrow transplantation

bone marrow or peripheral blood stem cells

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

DISEASE CHARACTERISTICS:

• Diagnosis of acute myeloid leukemia, lymphoblastic leukemia, or myelodysplastic syndrome

• Any phase allowed, including any of the following:

• Disease in remission
• Relapsed or primary refractory disease
• No CNS leukemic involvement not clearing with prior intrathecal chemotherapy and/or cranial radiotherapy
• Planning to undergo unmanipulated allogeneic bone marrow or peripheral blood stem cell transplantation

• Filgrastim (G-CSF) mobilization of bone marrow or stem cells allowed
• Donor available, meeting 1 of the following criteria:

• HLA-identical related donor
• HLA-A, -B, -C, -DRB1, and -DQB1 matched unrelated donor by high-resolution DNA typing

• A single allele mismatch allowed

PATIENT CHARACTERISTICS:

Performance status

• Karnofsky 70-100% OR
• Lansky 70-100%

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin ≤ 2 times upper limit of normal (ULN)
• AST ≤ 2 times ULN
• No evidence of synthetic dysfunction
• No severe cirrhosis
• No active infectious hepatitis

Renal

• Creatinine clearance ≥ 50%
• Creatinine ≤ 2 times ULN
• Dialysis independent

Cardiovascular

• No cardiac insufficiency requiring treatment
• No symptomatic coronary artery disease
• Ejection fraction ≥ 35% (for patients with history of cardiac disease or anthracycline exposure)

Pulmonary

• PO_2 ≥ 70 mm Hg AND DLCO ≥ 70% of predicted OR
• PO_2 ≥ 80 mm Hg AND DLCO ≥ 60% of predicted
• Not requiring supplementary continuous oxygen

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other disease that would severely limit life expectancy
• No HIV positivity
• No active infection requiring deferral of conditioning
• No known hypersensitivity to the study drugs

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics
• No prior allogeneic bone marrow or stem cell transplantation
• No concurrent umbilical cord blood or autologous transplantation

Chemotherapy

• See Disease Characteristics

Radiotherapy

• See Disease Characteristics

Other

• More than 4 weeks since prior experimental drugs
• Concurrent enrollment on another protocol for graft-versus-host disease prophylaxis allowed

• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

medac GmbH

INDUSTRY

Sponsor Role: collaborator

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

OHSU Knight Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eneida Nemecek, MD

Role: PRINCIPAL_INVESTIGATOR

OHSU Knight Cancer Institute

Locations

OHSU Knight Cancer Institute

Portland, Oregon, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Countries

United States

Other Identifiers

FHCRC-1931.00

Identifier Type: -

Identifier Source: secondary_id

MEDAC-FHCRC-1931.00

Identifier Type: -

Identifier Source: secondary_id

OHSU-HEM-05107-LM

Identifier Type: -

Identifier Source: secondary_id

1765

Identifier Type: OTHER

Identifier Source: secondary_id

CDR0000445306

Identifier Type: -

Identifier Source: org_study_id