Treosulfan, Fludarabine, Total-Body Irradiation, and Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia or Myelodysplastic Syndrome - Full Text View

Sponsors and Collaborators:	Fred Hutchinson Cancer Research Center National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00860574

Purpose

RATIONALE: Giving chemotherapy, such as treosulfan and fludarabine, and total-body irradiation before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and methotrexate before and after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving treosulfan together with fludarabine and total-body irradiation followed by donor stem cell transplant works in treating patients with high-risk acute myeloid leukemia or myelodysplastic syndrome.

Condition	Intervention	Phase
Leukemia Myelodysplastic Syndromes	Drug: fludarabine phosphate Drug: methotrexate Drug: tacrolimus Drug: treosulfan Procedure: allogeneic bone marrow transplantation Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Radiation: total-body irradiation	Phase II

MedlinePlus related topics: Bone Marrow Transplantation Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Radiation Therapy

Drug Information available for: Methotrexate Fludarabine Fludarabine monophosphate Tacrolimus anhydrous Tacrolimus Treosulfan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment
Official Title:	Conditioning With Treosulfan, Fludarabine And Escalating Doses of TBI for Allogeneic Hematopoietic Cell Transplantation in Patients With Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Incidence of relapse at 6 months [ Designated as safety issue: No ]
Non-relapse mortality at 6 months [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	April 2009
Estimated Primary Completion Date:	October 2011 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the efficacy of conditioning with treosulfan, fludarabine phosphate, and total-body irradiation followed by allogeneic stem cell transplantation in reducing the incidence of relapse to < 15% at 6 months post-transplant in patients with high-risk acute myeloid leukemia or myelodysplastic syndromes.

Secondary

Evaluate the incidence of non-relapse mortality at 180 days and 1 year after transplantation.
Evaluate the overall survival and relapse-free survival.
Evaluate the incidence of grades II-IV acute graft-versus-host disease (GVHD).
Evaluate the incidence of chronic GVHD.
Evaluate donor chimerism at 28 days and 100 days after transplantation

OUTLINE:

Conditioning regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -6 to -2 and treosulfan IV over 2 hours on days -6 to -4.

Patients also undergo total-body irradiation on day 0.

Transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0.
Graft-versus-host disease (GVHD) prophylaxis: Patients receive tacrolimus IV continuously or orally twice daily on days -1 to 56, followed by a taper until day 180 in the absence of GVHD. Patients also receive methotrexate IV on days 1, 3, 6, and 11.

Eligibility

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

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of one of the following:
- Acute myeloid leukemia (AML) meeting one of the following criteria:
  - Beyond first remission
  - Intermediate- or high-risk AML (based on SWOG cytogenetic criteria) in first complete remission
- Myelodysplastic syndromes with ≥ 5% blasts at any point prior to transplantation
No CNS leukemic involvement not clearing with intrathecal chemotherapy and/or cranial radiotherapy prior to initiation of conditioning regimen (day
- 6)
Available donor meeting one of the following criteria:
- HLA-identical related donor
- Unrelated donor matched for HLA-A, B, C, DRB1, and DQB1 alleles by high-resolution DNA typing OR mismatched for one HLA allele (HLA-A, B, DRB1, or DQB1; no mismatch at HLA-C)

PATIENT CHARACTERISTICS:

Karnofsky or Lansky performance status 80-100%
Life expectancy not severely limited by diseases other than this malignancy
Creatinine clearance ≥ 50% for age, weight, and height OR serum creatinine ≤ 2 times upper limit of normal (ULN)
Total bilirubin ≤ 2.0 times ULN
AST ≤ 2.0 times ULN
Ejection fraction ≥ 35%
pO2 ≥ 70 mm Hg and DLCO ≥ 70% of predicted OR pO2 ≥ 80 mm Hg and DLCO ≥ 60% of predicted
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
Not dialysis-dependent
No evidence of synthetic hepatic dysfunction or severe cirrhosis
No cardiac insufficiency requiring treatment
No symptomatic coronary artery disease
No requirement for supplementary continuous oxygen
No active infectious disease requiring deferral of conditioning, as recommended by an infectious disease specialist
No HIV-positivity or active infectious hepatitis
No known hypersensitivity to treosulfan and/or fludarabine phosphate

PRIOR CONCURRENT THERAPY:

Prior autologous or allogeneic hematopoietic stem cell transplantation allowed
More than 4 weeks since prior experimental drugs
No prior or concurrent umbilical cord blood transplantation

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00860574

Locations

United States, Washington
Fred Hutchinson Cancer Research Center	Recruiting
Seattle, Washington, United States, 98109-1024
Contact: Merav Bar, MD 206-667-4545
Seattle Cancer Care Alliance	Recruiting
Seattle, Washington, United States, 98109-1023
Contact: Clinical Trials Office - Seattle Cancer Care Alliance 800-804-8824

Sponsors and Collaborators

Fred Hutchinson Cancer Research Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Merav Bar, MD

Fred Hutchinson Cancer Research Center

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:	Fred Hutchinson Cancer Research Center ( Merav Bar )
Study ID Numbers:	CDR0000636834, FHCRC-2272.00, IR-6896
Study First Received:	March 11, 2009
Last Updated:	May 2, 2009
ClinicalTrials.gov Identifier:	NCT00860574 History of Changes
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

adult acute myeloid leukemia in remission
recurrent adult acute myeloid leukemia
childhood acute myeloid leukemia in remission
recurrent childhood acute myeloid leukemia
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)

adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
childhood myelodysplastic syndromes
previously treated myelodysplastic syndromes
de novo myelodysplastic syndromes
secondary myelodysplastic syndromes

Study placed in the following topic categories:

Antimetabolites
Precancerous Conditions
Immunologic Factors
Tacrolimus
Leukemia, Myeloid, Acute
Leukemia
Acute Myelocytic Leukemia
Preleukemia
Acute Myeloid Leukemia, Adult
Neoplasm Metastasis
Methotrexate
Congenital Abnormalities
Alkylating Agents
Hematologic Diseases

Myelodysplastic Syndromes
Leukemia, Myeloid
Fludarabine monophosphate
Folic Acid Antagonists
Immunosuppressive Agents
Recurrence
Acute Myeloid Leukemia, Childhood
Folic Acid
Antineoplastic Agents, Alkylating
Fludarabine
Bone Marrow Diseases
Treosulfan
Antirheumatic Agents

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Precancerous Conditions
Antineoplastic Agents
Physiological Effects of Drugs
Tacrolimus
Reproductive Control Agents
Leukemia, Myeloid, Acute
Leukemia
Preleukemia
Pathologic Processes
Syndrome
Therapeutic Uses

Abortifacient Agents
Methotrexate
Alkylating Agents
Dermatologic Agents
Nucleic Acid Synthesis Inhibitors
Disease
Neoplasms by Histologic Type
Hematologic Diseases
Myelodysplastic Syndromes
Enzyme Inhibitors
Leukemia, Myeloid
Fludarabine monophosphate
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Immunosuppressive Agents

ClinicalTrials.gov processed this record on May 07, 2009