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Donor Stem Cell Transplant After Busulfan, Fludarabine, and Antithymocyte Globulin in Treating Patients With Hematologic Cancer or Myelodysplastic Syndrome

Primary Purpose

Leukemia, Myelodysplastic Syndromes

Status

Completed

Phase

Phase 2

Locations

Korea, Republic of

Study Type

Interventional

Intervention

nonmyeloablative allogeneic hematopoietic stem cell transplantation

peripheral blood stem cell transplantation

About this trial

This is an interventional treatment trial for Leukemia focused on measuring accelerated phase chronic myelogenous leukemia, adult acute lymphoblastic leukemia in remission, adult acute myeloid leukemia in remission, acute undifferentiated leukemia, blastic phase chronic myelogenous leukemia, childhood acute lymphoblastic leukemia in remission, childhood acute myeloid leukemia in remission, childhood chronic myelogenous leukemia, childhood myelodysplastic syndromes, chronic phase chronic myelogenous leukemia, chronic myelomonocytic leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, recurrent childhood acute lymphoblastic leukemia, recurrent childhood acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, relapsing chronic myelogenous leukemia, secondary myelodysplastic syndromes

Eligibility Criteria

undefined - 75 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS:

Diagnosis of 1 of the following hematological malignancies:
- Acute leukemia, including any of the following:
  - Refractory acute leukemia
  - Acute leukemia beyond first remission
  - Acute leukemia in first remission with intermediate to poor prognostic features as suggested by chromosomal findings
- Chronic myelogenous leukemia (CML)
  - Second chronic phase
  - Accelerated phase
  - Blastic phase
- Myelodysplastic syndrome (MDS)
  - High-risk MDS (refractory anemia with excess blasts [RAEB], RAEB in transformation, and chronic myelomonocytic leukemia) can be transplanted without prior therapy or after prior therapy failure with hypomethylating agents
  - Low-risk MDS can be considered for transplantation after prior therapy failure with immunosuppressive or hypomethylating agents
No willing, suitable HLA-matched donor in family or in donor registries
- Patients with active hematologic malignancy, who are felt to be in urgent need of allogeneic hematopoietic cell transplantation, can enroll without a search for HLA-matched unrelated donors
Related donor with HLA-haploidentical mismatch at 3 or less of 6 loci available

PATIENT CHARACTERISTICS:

Karnofsky performance status 70-100%
Bilirubin < 2.0 mg/dL
Creatinine < 2.0 mg/dL
AST < 3 times upper limit of normal
Ejection fraction > 40% by MUGA

PRIOR CONCURRENT THERAPY:

See Disease Characteristics

Sites / Locations

Asan Medical Center - University of Ulsan College of Medicine

Outcomes

Primary Outcome Measures

tumor response

leukemia CR, CR duration

Secondary Outcome Measures

Donor cell engraftment (neutrophil, platelet, and red blood cells)

neutrophi count over 500/ul

Acute and chronic graft-versus-host disease

ocurrence of acute or chronic GVHD

Full Information

NCT ID

NCT00732316

First Posted

August 8, 2008

Last Updated

July 16, 2012

Sponsor

Asan Medical Center

Collaborators

Pusan National University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT00732316

Brief Title

Donor Stem Cell Transplant After Busulfan, Fludarabine, and Antithymocyte Globulin in Treating Patients With Hematologic Cancer or Myelodysplastic Syndrome

Official Title

HLA-HAPLOIDENTICAL FAMILIAL DONOR HEMATOPOIETIC CELL TRANSPLANTATION AFTER REDUCED INTENSITY CONDITIONING OF BUSULFAN, FLUDARABINE, AND ANTI-THYMOCYTE GLOBULIN FOR ADULT PATIENTS WITH HEMATOLOGIC MALIGNANCIES AND MYELODYSPLASTIC SYNDROME - A PHASE 2 STUDY

Study Type

Interventional

2. Study Status

Record Verification Date

July 2012

Overall Recruitment Status

Completed

Study Start Date

April 2008 (undefined)

Primary Completion Date

December 2009 (Actual)

Study Completion Date

May 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Asan Medical Center

Collaborators

Pusan National University Hospital

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

RATIONALE: Giving low doses of chemotherapy and antithymocyte globulin before a donor stem cell transplant helps stop the growth of cancer and abnormal 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 and abnormal cells (graft-versus-tumor effect). PURPOSE: This phase II trial is studying how well a donor stem cell transplant works after busulfan, fludarabine, and antithymocyte globulin in treating patients with hematologic cancer or myelodysplastic syndrome.

Detailed Description

OBJECTIVES: To evaluate the efficacy of HLA-haploidentical familial donor hematopoietic cell transplantation with a reduced-intensity conditioning regimen of busulfan, fludarabine phosphate, and anti-thymocyte globulin in patients with hematologic malignancies or myelodysplastic syndromes. OUTLINE: Before receiving the reduced-intensity conditioning regimen, patients receive one dose of intrathecal (IT) methotrexate, then leucovorin calcium IV or orally 4 hours after methotrexate and every 6 hours for a total of 8 doses. Reduced-intensity conditioning regimen: Patients receive busulfan IV over 6 hours on days -7 and -6, fludarabine phosphate IV over 30 minutes on days -7 to -2, anti-thymocyte globulin (ATG) IV over 4 hours on days -4 to -1, and methylprednisolone IV over 30 minutes on days -4 to -1. HLA-haploidentical familial donor hematopoietic stem cell transplantation (HSCT): Patients undergo allogeneic HSCT over 1 hour on days 0 and 1. Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV* over 2-4 hours every 12 hours on days -1 to 30 followed by a taper until day 60 and methotrexate IV on days 2, 4 , 7, and 12. NOTE: *Cyclosporine can be given orally once oral medication can be tolerated CNS prophylaxis: When blood counts recover, patients with acute leukemia or chronic myelogenous leukemia in blastic crisis resume IT methotrexate once every 2 weeks for a total of 4 doses (including the dose given before the conditioning regimen) and leucovorin calcium IV or orally 4 hours after (each dose of methotrexate) and every 6 hours for a total of 8 doses. After completion of study treatment, patients are followed periodically for up to 3 years.

6. Conditions and Keywords

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

Leukemia, Myelodysplastic Syndromes

Keywords

accelerated phase chronic myelogenous leukemia, adult acute lymphoblastic leukemia in remission, adult acute myeloid leukemia in remission, acute undifferentiated leukemia, blastic phase chronic myelogenous leukemia, childhood acute lymphoblastic leukemia in remission, childhood acute myeloid leukemia in remission, childhood chronic myelogenous leukemia, childhood myelodysplastic syndromes, chronic phase chronic myelogenous leukemia, chronic myelomonocytic leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, recurrent childhood acute lymphoblastic leukemia, recurrent childhood acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, relapsing chronic myelogenous leukemia, secondary myelodysplastic syndromes

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

54 (Actual)

8. Arms, Groups, and Interventions

Intervention Type

Procedure

Intervention Name(s)

nonmyeloablative allogeneic hematopoietic stem cell transplantation

Intervention Description

administration of conditioning therapy including immunosuppressive agents plus alkylating agents and infusing hematopoietic progenitor cells collected from the donor

Intervention Type

Procedure

Intervention Name(s)

peripheral blood stem cell transplantation

Intervention Description

infusion of donor hematopoietic cells collected by leukapheresis after mobilization with growth factor

Primary Outcome Measure Information:

Title

tumor response

Description

leukemia CR, CR duration

Time Frame

about 4-8 weeks after transplantation

Secondary Outcome Measure Information:

Title

Donor cell engraftment (neutrophil, platelet, and red blood cells)

Description

neutrophi count over 500/ul

Time Frame

10-35 days after transplantation

Title

Acute and chronic graft-versus-host disease

Description

ocurrence of acute or chronic GVHD

Time Frame

15-100 days; 100 days to 4 years

10. Eligibility

Sex

All

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

DISEASE CHARACTERISTICS: Diagnosis of 1 of the following hematological malignancies: Acute leukemia, including any of the following: Refractory acute leukemia Acute leukemia beyond first remission Acute leukemia in first remission with intermediate to poor prognostic features as suggested by chromosomal findings Chronic myelogenous leukemia (CML) Second chronic phase Accelerated phase Blastic phase Myelodysplastic syndrome (MDS) High-risk MDS (refractory anemia with excess blasts [RAEB], RAEB in transformation, and chronic myelomonocytic leukemia) can be transplanted without prior therapy or after prior therapy failure with hypomethylating agents Low-risk MDS can be considered for transplantation after prior therapy failure with immunosuppressive or hypomethylating agents No willing, suitable HLA-matched donor in family or in donor registries Patients with active hematologic malignancy, who are felt to be in urgent need of allogeneic hematopoietic cell transplantation, can enroll without a search for HLA-matched unrelated donors Related donor with HLA-haploidentical mismatch at 3 or less of 6 loci available PATIENT CHARACTERISTICS: Karnofsky performance status 70-100% Bilirubin < 2.0 mg/dL Creatinine < 2.0 mg/dL AST < 3 times upper limit of normal Ejection fraction > 40% by MUGA PRIOR CONCURRENT THERAPY: See Disease Characteristics

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Kyoo H. Lee, MD

Organizational Affiliation

Asan Medical Center

Official's Role

Principal Investigator

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

21715313

Citation

Lee KH, Lee JH, Lee JH, Kim DY, Seol M, Lee YS, Kang YA, Jeon M, Hwang HJ, Jung AR, Kim SH, Yun SC, Shin HJ. Reduced-intensity conditioning therapy with busulfan, fludarabine, and antithymocyte globulin for HLA-haploidentical hematopoietic cell transplantation in acute leukemia and myelodysplastic syndrome. Blood. 2011 Sep 1;118(9):2609-17. doi: 10.1182/blood-2011-02-339838. Epub 2011 Jun 28.

Results Reference

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Donor Stem Cell Transplant After Busulfan, Fludarabine, and Antithymocyte Globulin in Treating Patients With Hematologic Cancer or Myelodysplastic Syndrome

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