Clinical trial NCT00619645: Donor Peripheral Stem Cell Transplant, Fludarabine, and Busulfan in Treating Patients With Hematologic Cancers
Official title: Reduced Intensity Stem Cell Transplantation (RIST) for Patients With Hematological Malignancies Conditioned With Fludarabine and Busulfan
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Keywords: recurrent adult acute myeloid leukemia
adult acute lymphoblastic leukemia in remission
refractory anemia with excess blasts
refractory anemia with ringed sideroblasts
refractory anemia
refractory cytopenia with multilineage dysplasia
previously treated myelodysplastic syndromes
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia in remission
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)
chronic phase chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
refractory chronic lymphocytic leukemia
recurrent adult Hodgkin lymphoma
refractory multiple myeloma
recurrent adult acute lymphoblastic leukemia
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
secondary acute myeloid leukemia
recurrent small lymphocytic lymphoma
stage III small lymphocytic lymphoma
stage IV small lymphocytic lymphoma
stage III grade 1 follicular lymphoma
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage IV grade 1 follicular lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
stage III adult diffuse large cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage IV adult lymphoblastic lymphoma
recurrent adult lymphoblastic lymphoma
stage III adult Burkitt lymphoma
stage IV adult Burkitt lymphoma
recurrent adult Burkitt lymphoma
stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma
de novo myelodysplastic syndromes
secondary myelodysplastic syndromes
Lead sponsor: University of California, Davis
Sponsor class: OTHER
First posted: 2008-02-21
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Giving chemotherapy drugs, such as fludarabine and busulfan, before a donor peripheral stem cell transplant helps stop the growth of cancer cells. It 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 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 before and after the transplant may stop this from happening.

PURPOSE: This phase II trial is studying the side effects of giving donor peripheral stem cell transplant together with fludarabine and busulfan and to see how well it works in treating patients with hematologic cancers.

Detailed description: OUTLINE:

* Conditioning regimen: Patients receive busulfan IV over 3 hours on days -6 and -5 and fludarabine phosphate IV over 30 minutes on days -6 to -2.
* Allogeneic peripheral blood stem cell transplant (PBSC): Patients undergo allogeneic PBSC on day 0.
* Immunosuppressive therapy/graft-versus-host disease (GVHD) prophylaxis: Patients achieve100% donor T-cell chimerism on day 30 without disease recurrence, and cyclosporine A (CSA) IV continuously over 24 hours or orally every 12 hours on days -1 to 60 followed by a taper until day 100 and oral mycophenolate mofetil (MMF) once every 12 hours on days 1-40, in the absence of ≥ grade 2 GVHD.

Patients with recurrent disease or \< 100% donor T-cell chimerism (on day 30) undergo a 12-day CSA and MMF taper followed by escalating doses of previously collected donor leukocyte infusion every 4 weeks until 100% donor T-cell chimerism or disease regression, in the absence of ≥ grade 2 GVHD.

After completion of study treatment, patients are followed periodically.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Diagnosed with any of the following:

  * Acute myeloid leukemia (AML), meeting 1 of the following criteria:

    * Recurrent disease in remission, defined as morphological remission with bone marrow aspirate/biopsy showing ≤ 5% within 4 weeks before the start of study treatment (cytogenetic or molecular remission is not required)
    * In first complete remission (CR1) with poor-risk cytogenetics, antecedent hematological disease (i.e., myelodysplasia), or treatment-related leukemia
  * Acute lymphoblastic leukemia (ALL), meeting 1 of the following criteria:

    * Recurrent disease in remission, defined as morphological remission with bone marrow aspirate/biopsy showing ≤ 5% within 4 weeks before the start of study treatment (cytogenetic or molecular remission is not required)
    * CR1 with Philadelphia chromosome or poor-risk cytogenetics
  * Chronic myelogenous leukemia (CML), meeting the following criteria:

    * First or second chronic phase

      * Must be documented disease progression after imatinib mesylate therapy OR documented lack of cytogenetic response 6 months post-imatinib mesylate initiation OR imatinib mesylate intolerance
  * Chronic lymphocytic leukemia (CLL), meeting the following criteria:

    * Recurrent disease after fludarabine-based therapy

      * Must have chemosensitive disease at the time of relapse, defined as greater than 50% reduction of WBC and lymphadenopathy
  * Recurrent Hodgkin lymphoma, recurrent non-Hodgkin lymphoma (NHL) (low-, intermediate-, or high-grade disease\*), or transformed NHL, meeting 1 of the following criteria:

    * Received prior autologous transplantation and cytoreductive therapy at the time of relapse to achieve complete remission (CR) or CR/unconfirmed (CRu) as defined by the International Workshop
    * Relapsed disease that required more than 2 salvage regimens to achieve CR or CRu
  * Recurrent multiple myeloma, meeting the following criteria:

    * Must have received prior autologous transplantation and demonstrate chemosensitivity at the time of relapse, defined as greater than 50% reduction of M-component or plasma-cell marrow infiltration
  * Myelodysplastic syndrome

    * Refractory anemia (RA)/RA with ringed sideroblasts (RARS), refractory cytopenia with multilineage dysplasia (RCMD)/refractory cytopenia with multilineage dysplasia with ringed sideroblasts (RCMD-RS), or RA with excess blasts (RAEB) I, meeting the following criteria:

      * Must be transfusion-dependent and have an IPSS score ≥ 1.5, based on WHO criteria
      * No RAEB II or del(5q)
* No uncontrolled CNS metastases
* 5-6/6 HLA-matched sibling or 9-10/10 matched unrelated donor (both patient and donor) available

PATIENT CHARACTERISTICS:

* Karnofsky performance status ≥ 50%
* Serum creatinine ≤ 2 mg/dL
* Not pregnant
* Fertile patients must use effective contraception
* 50 years of age or older

  * Patients 18-50 years of age are eligible if meeting 1 of the following criteria:

    * Have a preexisting medical condition
    * Received prior therapy (i.e., autologous transplantation) and are considered to be too high risk for conventional myeloablative transplantation
* Must be willing to accept or comprehend irreversible sterility as a side effect of therapy
* No uncontrolled active infection
* No psychiatric illness or mental deficiency making compliance with treatment or informed consent impossible
* Cardiac ejection fraction ≥ 30%
* Corrected pulmonary-diffusing capacity ≥ 35%
* No serologic evidence of infection with HIV
* No decompensated liver disease with serum bilirubin \> 2.0 mg/dL

PRIOR CONCURRENT THERAPY:

* See Disease Characteristics

Primary outcomes:
measure: Number of Patients With Day 100 Transplant-related Mortality
timeFrame: 24 months after day 100 transplant
Secondary outcomes:
measure: Number of Patients Without Progression After Day 100 Transplant
timeFrame: 24 months after day 100 transplant
measure: Number of Patients Alive 24 Months Post Day 100 Transplant
timeFrame: 24 months post day 100 transplant
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: University of California Davis Cancer Center
state: California
Study officials:
affiliation: University of California, Davis
name: Carol M. Richman, MD
role: STUDY_CHAIR
References: