Clinical trial NCT00732316: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: Asan Medical Center
Sponsor class: OTHER
Collaborators: name: Pusan National University Hospital
First posted: 2008-08-11
Enrollment: 54
Sex: ALL
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: tumor response
timeFrame: about 4-8 weeks after transplantation
Secondary outcomes:
measure: Donor cell engraftment (neutrophil, platelet, and red blood cells)
timeFrame: 10-35 days after transplantation
measure: Acute and chronic graft-versus-host disease
timeFrame: 15-100 days; 100 days to 4 years
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center - University of Ulsan College of Medicine
Study officials:
affiliation: Asan Medical Center
name: Kyoo H. Lee, MD
role: PRINCIPAL_INVESTIGATOR
References:
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.