Clinical trial NCT00521430: Donor Stem Cell Transplant After Conditioning Therapy in Treating Patients With Hematologic Cancer, Recurrent or Metastatic Solid Tumor, or Other Disease
Official title: NON-T-CELL DEPLETED HLA-HAPLOIDENTICAL FAMILIAL DONOR HEMATOPOIETIC CELL TRANSPLANTATION AFTER REDUCED INTENSITY CONDITIONING
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Nonmalignant Neoplasm
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: recurrent childhood grade III lymphomatoid granulomatosis
childhood diffuse large cell lymphoma
recurrent childhood large cell lymphoma
childhood immunoblastic large cell lymphoma
recurrent childhood lymphoblastic lymphoma
childhood nasal type extranodal NK/T-cell lymphoma
recurrent childhood small noncleaved cell lymphoma
adult acute myeloid leukemia in remission
adult acute lymphoblastic leukemia in remission
aplastic anemia
recurrent childhood acute lymphoblastic leukemia
childhood acute lymphoblastic leukemia in remission
childhood acute myeloid leukemia in remission
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)
refractory anemia with excess blasts in transformation
refractory anemia with excess blasts
refractory anemia with ringed sideroblasts
refractory anemia
refractory multiple myeloma
chronic myelomonocytic leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
recurrent adult Hodgkin lymphoma
recurrent adult T-cell leukemia/lymphoma
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent mycosis fungoides/Sezary syndrome
adult nasal type extranodal NK/T-cell lymphoma
Waldenström macroglobulinemia
recurrent adult Burkitt lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult grade III lymphomatoid granulomatosis
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
cutaneous B-cell non-Hodgkin lymphoma
unspecified adult solid tumor, protocol specific
childhood chronic myelogenous leukemia
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma
recurrent adult acute lymphoblastic leukemia
recurrent adult acute myeloid leukemia
recurrent childhood acute myeloid leukemia
recurrent/refractory childhood Hodgkin lymphoma
secondary myelodysplastic syndromes
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2007-08-27
Enrollment: 30
Sex: ALL
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Giving chemotherapy before a donor stem cell transplant helps stop the growth of cancer or abnormal cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine and methotrexate before and after transplant may stop this from happening.

PURPOSE: This clinical trial is studying the side effects and how well donor stem cell transplant works when given after conditioning therapy in treating patients with hematologic cancer, recurrent or metastatic solid tumor, or other disease.

Detailed description: OBJECTIVES:

* Determine the safety and efficacy of non-T-cell depleted, HLA-haploidentical related donor hematopoietic stem cell transplantation after a reduced-intensity conditioning regimen comprising busulfan, fludarabine phosphate, anti-thymocyte globulin, and methylprednisolone in patients with hematologic cancer, recurrent or metastatic solid tumors, or other diseases.

OUTLINE:

* Reduced-intensity conditioning regimen: Patients receive busulfan IV 4 times daily on days -7 and -6; fludarabine phosphate IV over 30 minutes on days -7 to -2; and methylprednisolone IV over 30 minutes followed by anti-thymocyte globulin IV over 4 hours on days -4 to -1.
* Donor hematopoietic stem cell transplantation: Patients receive donor peripheral blood stem cells IV over 1 hour on days 0 and 1.
* Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV over 2-4 hours or orally twice daily beginning on day -1 and continuing until day 60, followed by a taper in the absence of GVHD. Patients also receive methotrexate IV on days 2, 4, 7, and 12.

After the transplant, patients are followed periodically.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of 1 of the following:

  * High-risk acute leukemia, including any of the following:

    * Refractory acute leukemia
    * Acute leukemia beyond first remission
    * Acute leukemia in first remission with poor prognostic features (e.g., chromosomal changes suggesting poor prognosis)
  * Chronic myelogenous leukemia in second chronic, accelerated, or blastic phase
  * Severe aplastic anemia that is not responsive to immunosuppressive therapy
  * Myelodysplastic syndromes, including any of the following:

    * Refractory anemia (RA) or RA with ringed sideroblasts with severe cytopenia
    * RA with excess blasts (RAEB)
    * RAEB in transformation
    * Chronic myelomonocytic leukemia
  * Refractory or relapsed non-Hodgkin or Hodgkin lymphoma
  * Multiple myeloma
  * Biopsy proven measurable solid tumor meeting 1 of the following criteria:

    * Recurrent disease after primary treatment and deemed incurable to standard treatment
    * Metastatic disease for which no known standard therapy that is potentially curative or definitely capable of extending life expectancy exists
* Must have a related HLA-haploidentical mismatched (3/6 or fewer loci) donor available

PATIENT CHARACTERISTICS:

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

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics

Primary outcomes:
measure: Engraftment (neutrophil, platelet, and red blood cells)
measure: Frequency and kinetics of mixed chimerism as assessed by polymerase chain reaction
measure: Frequency and severity of regimen-related toxicities
measure: Frequency of acute and chronic graft-versus-host disease
measure: Immune reconstitution
Secondary outcomes:
measure: Tumor response rate
measure: Duration of tumor response
measure: Survival
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: STUDY_CHAIR
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.