Clinical trial NCT00740467: Stem Cell Transplant in Treating Patients With Hematological Cancer or Other Disorders
Official title: Allograft of Hematopoietic Stem Cells With Reduced-intensity Conditioning From a HLA-haploidentical Family Donor: Phase II Study of Combined Immunosuppression Before and After Transplantation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Graft Versus Host Disease
Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Precancerous Condition
Keywords: graft versus host disease
adult 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)
recurrent adult acute myeloid leukemia
adult acute lymphoblastic leukemia in remission
recurrent adult acute lymphoblastic leukemia
accelerated phase chronic myelogenous leukemia
chronic phase chronic myelogenous leukemia
refractory multiple myeloma
relapsing chronic myelogenous leukemia
recurrent adult Hodgkin lymphoma
adult nasal type extranodal NK/T-cell lymphoma
anaplastic large cell lymphoma
angioimmunoblastic T-cell lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
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 adult T-cell leukemia/lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent grade I lymphomatoid granulomatosis
recurrent grade II lymphomatoid granulomatosis
recurrent mantle cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
splenic marginal zone lymphoma
refractory chronic lymphocytic leukemia
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2008-08-25
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

Brief summary: RATIONALE: Giving chemotherapy, such as fludarabine, busulfan, and cyclophosphamide, together with antithymocyte globulin before a donor stem cell transplant helps stop the growth of cancer and abnormal cells. Giving chemotherapy before or after transplant also stops 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). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well stem cell transplant works in treating patients with hematological cancer or other disorders.

Detailed description: OBJECTIVES:

Primary

* Evaluate the incidence of graft acceptance in patients with hematological disorders treated with combined immunosuppression before and after HLA-haploidentical hematopoietic stem cell transplantation.

Secondary

* Evaluate efficacy of this regimen in these patients.
* Evaluate toxicity of this regimen in these patients.
* Assess survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

* Reduced-intensity conditioning: Patients receive fludarabine phosphate IV on days -6 to -1, busulfan IV on days -6 to -5, and anti-thymocyte globulin IV on days -4 to -1.
* Transplantation: Patients undergo transplantation of donor hematopoietic stem cells on day 0. Patients also receive cyclophosphamide IV on day 3 and filgrastim (G-CSF) beginning on day 4 and continuing until blood counts recover.
* Immunosuppression: Patients receive cyclosporine IV beginning on day -2 and continuing for 6 months and mycophenolate mofetil 4 times a day on days 4-84.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosis of any of the following hematological cancers with a poor prognosis:

  * Acute myeloid leukemia meeting 1 of the following criteria:

    * Third complete remission (CR3) or beyond
    * CR2 after an early bone marrow relapse (\< 24 months)
    * Refractory disease after ≥ 2 chemotherapy courses of induction therapy
  * Acute lymphoblastic leukemia meeting 1 of the following criteria:

    * CR3 after ≥ 1 bone marrow relapse
    * CR2 after early bone marrow relapse (currently or within 6 months after stopping maintenance therapy)
  * Chronic myelogenous leukemia meeting the following criteria:

    * Accelerated phase
    * Second chronic phase
    * No other treatment options
  * Multiple myeloma meeting the following criteria:

    * Failed conventional therapy (including autologous hematopoietic stem cell transplantation)
    * No other treatment alternatives
  * Chronic lymphocytic leukemia meeting the following criteria:

    * Failed conventional therapy
    * No other treatment alternatives
  * Hodgkin lymphoma meeting the following criteria:

    * Failed conventional therapy
    * No other treatment alternatives
  * Non-Hodgkin lymphoma meeting the following criteria:

    * Failed conventional therapy
    * No other treatment alternatives
* Not eligible for standard myeloablative allograft due to increased toxicity
* Healthy related donor available and meeting the following criteria:

  * Brother, sister, father, mother, cousin, uncle, or aunt
  * At least an identical HLA haplotype

    * Identical genotype on 1 haplotype (in terms of HLA-A, B, C, and DR)
    * Different on ≤ 4 alleles on the other haplotype
* No HLA-identical intra- or extra-familial donor cord blood available within the next 3 months

PATIENT CHARACTERISTICS:

* Karnofsky performance status 70-100%
* Not pregnant or nursing
* Fertile patients must use effective contraception
* No contraindication to allogeneic transplantation, including any of the following:

  * Cardiac systolic ejection fraction \< 40%
  * DLCO level limiting use of fludarabine
  * Creatinine clearance \< 30 mL/min
  * Transaminases and/or bilirubin \> 3 times upper limit of normal (unless due to Gilbert disease or cancer)
  * HIV seropositivity
  * Human T-cell lymphotrophic virus type 1 seropositivity
  * Uncontrolled bacterial, viral, or fungal infection
* No contraindication to any of the study drugs
* No prior or concurrent psychiatric illness
* No other cancer in the past 5 years except for basal cell skin cancer or carcinoma in situ of the cervix
* No concurrent serious, uncontrolled condition
* No patients deprived of liberty or subject to legal protection

PRIOR CONCURRENT THERAPY:

* No participation in a study of allografts in the past month

Primary outcomes:
measure: Incidence of graft acceptance
Secondary outcomes:
Other outcomes:
Locations:
city: Marseille
country: France
facility: Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes
Study officials:
affiliation: Institut Paoli-Calmettes
name: Didier Blaise, MD
role: STUDY_CHAIR
References: