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

Primary Purpose

Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms

Status

Completed

Phase

Phase 2

Locations

Korea, Republic of

Study Type

Interventional

Intervention

anti-thymocyte globulin

busulfan

fludarabine phosphate

leucovorin calcium

methotrexate

allogeneic bone marrow transplantation

allogeneic hematopoietic stem cell transplantation

nonmyeloablative allogeneic hematopoietic stem cell transplantation

About this trial

This is an interventional treatment trial for Leukemia focused on measuring 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, BCR-ABL1 negative, myelodysplastic/myeloproliferative neoplasm, unclassifiable, refractory anemia with excess blasts in transformation, refractory anemia with excess blasts

Eligibility Criteria

15 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Asan Medical Center - University of Ulsan College of Medicine

Outcomes

Primary Outcome Measures

Treatment-related mortality

Engraftment

Secondary Outcome Measures

Regimen-related toxicities

Graft-versus-host-disease

Relapse

Overall survival

Failure-free survival

100-day transplant-related mortality

Full Information

NCT ID

NCT00627666

First Posted

February 29, 2008

Last Updated

March 25, 2013

Sponsor

Asan Medical Center

1. Study Identification

Unique Protocol Identification Number

NCT00627666

Brief Title

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

Official Title

Unrelated Donor Hematopoietic Stem Cell Transplantation After Nonmyeloablative Conditioning For Patients With Hematological Malignancies

Study Type

Interventional

2. Study Status

Record Verification Date

July 2009

Overall Recruitment Status

Completed

Study Start Date

January 2003 (undefined)

Primary Completion Date

June 2010 (Actual)

Study Completion Date

June 2010 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Asan Medical Center

4. Oversight

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms

Keywords

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, BCR-ABL1 negative, myelodysplastic/myeloproliferative neoplasm, unclassifiable, refractory anemia with excess blasts in transformation, refractory anemia with excess blasts

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Masking

None (Open Label)

Enrollment

52 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type

Biological

Intervention Name(s)

anti-thymocyte globulin

Intervention Type

Drug

Intervention Name(s)

busulfan

Intervention Type

Drug

Intervention Name(s)

fludarabine phosphate

Intervention Type

Drug

Intervention Name(s)

leucovorin calcium

Intervention Type

Drug

Intervention Name(s)

methotrexate

Intervention Type

Procedure

Intervention Name(s)

allogeneic bone marrow transplantation

Intervention Type

Procedure

Intervention Name(s)

allogeneic hematopoietic stem cell transplantation

Intervention Type

Procedure

Intervention Name(s)

nonmyeloablative allogeneic hematopoietic stem cell transplantation

Primary Outcome Measure Information:

Title

Treatment-related mortality

Title

Engraftment

Secondary Outcome Measure Information:

Title

Regimen-related toxicities

Title

Graft-versus-host-disease

Title

Relapse

Title

Overall survival

Title

Failure-free survival

Title

100-day transplant-related mortality

10. Eligibility

Sex

All

Minimum Age & Unit of Time

15 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kyoo H. Lee, MD

Organizational Affiliation

Asan Medical Center

Official's Role

Study Chair

Facility Information:

Facility Name

Asan Medical Center - University of Ulsan College of Medicine

City

Seoul

ZIP/Postal Code

138-736

Country

Korea, Republic of

12. IPD Sharing Statement

Citations:

PubMed Identifier

21523798

Citation

Lee KH, Choi SJ, Lee JH, Lee JH, Kim DY, Seol M, Lee YS, Kang YA, Jeon M, Yun SC, Joo YD, Lee WS, Kang MJ, Kim H, Park JH, Bae SH, Ryoo HM, Kim MK, Hyun MS. Clinical effect of reduced-intensity conditioning regimen containing antithymocyte globulin for hematopoietic cell transplantation from unrelated-donors. Am J Hematol. 2011 May;86(5):399-405. doi: 10.1002/ajh.21989.

Results Reference

result

Learn more about this trial

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

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