Donor Stem Cell Transplant After Busulfan, Fludarabine, and Antithymocyte Globulin in Treating Patients With Hematological Cancer - Full Text View

Sponsored by:	Asan Medical Center
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00627666

Purpose

RATIONALE: Giving chemotherapy before a donor bone marrow stem cell transplant helps stop the growth of cancer cells. Chemotherapy and antithymocyte globulin 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 cyclosporine and methotrexate after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving donor stem cell transplant together with busulfan, fludarabine, and antithymocyte globulin works in treating patients with hematological cancer.

Condition	Intervention	Phase
Leukemia Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Diseases	Drug: anti-thymocyte globulin Drug: busulfan Drug: fludarabine phosphate Drug: leucovorin calcium Drug: methotrexate Procedure: allogeneic bone marrow transplantation Procedure: allogeneic hematopoietic stem cell transplantation Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation	Phase II

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

Drug Information available for: Leucovorin Calcium Citrovorum factor Folinic acid calcium salt pentahydrate Leucovorin Methotrexate Fludarabine Fludarabine monophosphate Calcium gluconate Busulfan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	Unrelated Donor Hematopoietic Stem Cell Transplantation After Nonmyeloablative Conditioning For Patients With Hematological Malignancies

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

Primary Outcome Measures:

Treatment-related mortality [ Designated as safety issue: Yes ]
Engraftment [ Designated as safety issue: No ]

Secondary Outcome Measures:

Regimen-related toxicities [ Designated as safety issue: Yes ]
Graft-versus-host-disease [ Designated as safety issue: Yes ]
Relapse [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Failure-free survival [ Designated as safety issue: No ]
100-day transplant-related mortality [ Designated as safety issue: Yes ]

Estimated Enrollment:	52
Study Start Date:	January 2003
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

To investigate whether unrelated donor hematopoietic stem cell transplantation using a nonmyeloablative conditioning regimen comprising busulfan, fludarabine phosphate, and anti-thymocyte globulin can reduce treatment-related mortality in patients with hematologic malignancies.
To investigate whether this regimen can be sufficiently immunosuppressive to enable engraftment of HLA-matched unrelated hematopoietic stem cells.

OUTLINE: This is a multicenter study.

Prior to receiving the conditioning chemotherapy regimen, all patients with acute leukemia, chronic myelogenous leukemia (CML), and high-risk myelodysplastic syndromes (chronic myelomonocytic leukemia, atypical CML, and refractory anemia with excess blasts) receive one dose of intrathecal (IT) methotrexate. These patients also receive leucovorin calcium IV or orally 4 hours after IT methotrexate and every 6 hours for a total of 8 doses.

Nonmyeloablative conditioning regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -2, busulfan IV over 3 hours on days -7 to -6, anti-thymocyte globulin IV over 4 hours on days -4 to -2.
Allogeneic bone marrow stem cell transplantation (SCT): Patients undergo allogeneic bone marrow SCT on day 0.
Graft-versus-host-disease (GVHD) prophylaxis: Patients receive cyclosporine (CSA) IV over 2-4 hours every 12 hours starting on day -1 and continuing until day 180 (CSA can be given orally every 12 hours once oral medication can be tolerated) and methotrexate IV on days 1, 3 , 6 , and 11.

Once blood counts recover, patients with acute leukemia or CML in blast crisis resume IT methotrexate once every 2 weeks for a total of 3 doses. Patients also receive leucovorin calcium IV or orally 4 hours after IT methotrexate and then every 6 hours for a total of 8 doses.

Patients are followed for at least 10 years after SCT.

Eligibility

Ages Eligible for Study:	15 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of any 1 of the following:
- Acute leukemia
- Chronic myelogenous leukemia
- Myelodysplastic syndromes
Must have an unrelated donor available who is matched for HLA-A and -B by serology and for DRB1 by molecular typing

PATIENT CHARACTERISTICS:

Karnofsky performance status 70-100%
Bilirubin < 3.0 mg/dL
Creatinine < 2.0 mg/dL
AST and ALT < 3 times the upper limit of normal
Not pregnant or nursing
Ejection fraction ≥ 45% by MUGA scan or ECHO
No major illness or organ failure
No severe psychiatric disorder or mental deficiency that makes compliance with the treatment unlikely and informed consent impossible

PRIOR CONCURRENT THERAPY:

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00627666

Locations

Korea, Republic of
Asan Medical Center - University of Ulsan College of Medicine	Recruiting
Seoul, Korea, Republic of, 138-736
Contact: Kyoo H. Lee, MD 82-2-2224-3210 khlee2@amc.seoul.kr

Sponsors and Collaborators

Asan Medical Center

Investigators

Study Chair:

Kyoo H. Lee, MD

Asan Medical Center

More Information

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

Study ID Numbers:	CDR0000583220, AMC-UUCM-2003-0207
Study First Received:	February 29, 2008
Last Updated:	September 22, 2008
ClinicalTrials.gov Identifier:	NCT00627666
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

adult acute lymphoblastic leukemia in remission
recurrent adult acute lymphoblastic leukemia
untreated adult acute lymphoblastic leukemia
adult acute myeloid leukemia in remission
recurrent adult acute myeloid leukemia
untreated adult acute myeloid leukemia
acute lymphocytic leukemia
secondary acute myeloid leukemia
acute undifferentiated leukemia
mast cell leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
meningeal chronic myelogenous leukemia

relapsing chronic myelogenous leukemia
chronic myelomonocytic 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)
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
atypical chronic myeloid leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
refractory anemia with excess blasts in transformation
refractory anemia with excess blasts

Study placed in the following topic categories:

Blast Crisis
Leukemia, Lymphoid
Chronic myelogenous leukemia
Precancerous Conditions
Chronic myelomonocytic leukemia
Refractory anemia
Leucovorin
Leukemia, Myeloid, Chronic-Phase
Leukemia, Myeloid, Acute
Acute lymphoblastic leukemia, adult
Leukemia
Preleukemia
Anemia, Refractory
Neoplasm Metastasis
Methotrexate

Acute myeloid leukemia, adult
Congenital Abnormalities
Leukemia, mast-cell
Acute myelocytic leukemia
Myelodysplastic syndromes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Hematologic Diseases
Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative
Leukemia, Myelomonocytic, Chronic
Leukemia, Mast-Cell
Myelodysplasia
Myelodysplastic Syndromes
Acute myelogenous leukemia
Myeloproliferative Disorders
Anemia

Additional relevant MeSH terms:

Antimetabolites
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Reproductive Control Agents
Pathologic Processes
Syndrome
Therapeutic Uses
Vitamins
Abortifacient Agents
Micronutrients
Alkylating Agents
Dermatologic Agents

Nucleic Acid Synthesis Inhibitors
Disease
Neoplasms by Histologic Type
Vitamin B Complex
Growth Substances
Enzyme Inhibitors
Folic Acid Antagonists
Abortifacient Agents, Nonsteroidal
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Antirheumatic Agents

ClinicalTrials.gov processed this record on January 16, 2009