Antithymocyte Globulin, Clofarabine, and Rituximab in Treating Patients After an Unsuccessful Stem Cell Transplant
Condition: Cancer
Intervention: anti-thymocyte globulin; rituximab; clofarabine; stem cell transplantation
Intervention description: administer 3 mg/kg intravenously (IV) over 4 hours on days -6, -5 and -4.; administered 375 mg/m^2 intravenously (IV) in 1 mg/mL normal saline on day -7.; administered 30 mg/m^2 intravenously (IV) over 1 hour on Days -4, -3, and -2.; administered on Day 0 per institutional guidelines.
Intervention MeSH terms: Rituximab; Clofarabine; Thymoglobulin; Antilymphocyte Serum
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 12.0
Sex: All
Healthy volunteers: No
Keywords: chronic myelogenous leukemia; acute lymphoblastic leukemia; chronic myeloid leukemia; lymphoblastic leukemia; acute myeloid leukemia; chronic eosinophilic leukemia; primary myelofibrosis; chronic myelomonocytic leukemia; chronic neutrophilic leukemia; de novo myelodysplastic syndromes; disseminated neuroblastoma; juvenile myelomonocytic leukemia; Burkitt lymphoma; rhabdomyosarcoma; myelodysplastic syndromes; Hodgkin lymphoma; lymphoblastic lymphoma; breast cancer; follicular lymphoma; mantle cell lymphoma; marginal zone lymphoma; recurrent neuroblastoma; recurrent ovarian epithelial cancer; recurrent ovarian germ cell tumor; recurrent small lymphocytic lymphoma; recurrent malignant testicular germ cell tumor; recurrent Wilms tumor and other childhood kidney tumors; recurrent/refractory childhood Hodgkin lymphoma; refractory hairy cell leukemia; refractory multiple myeloma; relapsing chronic myelogenous leukemia; secondary acute myeloid leukemia; secondary myelodysplastic syndromes; splenic marginal zone lymphoma; stage I multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; stage II ovarian epithelial cancer; stage III adult Burkitt lymphoma; stage III adult diffuse large cell lymphoma; stage III adult diffuse mixed cell lymphoma; stage III adult diffuse small cleaved cell lymphoma; stage III adult Hodgkin lymphoma; stage III adult immunoblastic large cell lymphoma; stage III adult lymphoblastic lymphoma; stage III chronic lymphocytic leukemia; stage III grade 1 follicular lymphoma; stage III grade 2 follicular lymphoma; stage III grade 3 follicular lymphoma; stage III mantle cell lymphoma; stage III marginal zone lymphoma; stage III ovarian epithelial cancer; stage III small lymphocytic lymphoma; stage III malignant testicular germ cell tumor; stage IIIA breast cancer; stage IIIB breast cancer; stage IIIC breast cancer; stage IV adult Burkitt lymphoma; stage IV adult diffuse large cell lymphoma; stage IV adult diffuse mixed cell lymphoma; stage IV adult diffuse small cleaved cell lymphoma; stage IV adult Hodgkin lymphoma; stage IV adult immunoblastic large cell lymphoma; stage IV adult lymphoblastic lymphoma; stage IV breast cancer; stage IV chronic lymphocytic leukemia; stage IV grade 1 follicular lymphoma; stage IV grade 2 follicular lymphoma; stage IV grade 3 follicular lymphoma; stage IV mantle cell lymphoma; stage IV marginal zone lymphoma; stage IV ovarian epithelial cancer; stage IV small lymphocytic lymphoma; refractory chronic lymphocytic leukemia

Summary:

      RATIONALE: Antithymocyte globulin, clofarabine, and rituximab may stop the patient's immune
      system from rejecting the donor's stem cells when they do not exactly match the patient's
      blood. 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 antithymocyte
      globulin before transplant and cyclosporine and mycophenolate mofetil before and after
      transplant may stop this from happening.

      PURPOSE: This phase II trial is studying how well giving antithymocyte globulin together with
      clofarabine and rituximab works in treating patients after an unsuccessful stem cell
      transplant.
    

Eligibility criteria:

        Patient Inclusion Criteria:

          -  Timing of relevant evaluations: Taking in account the need for rapid intervention, if
             white blood count is less than 200 on day +20, bone marrow aspirate should be
             performed on day +21. Unless there is an increase in absolute neutrophil count (ANC)
             to > 500 in the following 7 days, bone marrow aspirate should be repeated on day +28.
             If the white blood count is still less than 200 and bone marrow is acellular, bone
             marrow (BM) or peripheral blood stem cell (PBSC) donor should be reactivated and
             availability of cord blood (CB) units assessed. If the BM or PBSC donor is not
             confirmed within 14 days of the request for the donation (typically second donation
             from the same donor), CB unit should be used instead.

        Primary or secondary graft failure after hematopoietic stem cell transplantation defined as
        a > 50% loss of donor chimerism from previous maximum or less than 25% donor beyond day +42
        with pancytopenia and no evidence of relapse. Patients with any diagnosis, type of donor,
        hematopoietic cell graft or conditioning regimen should be considered for this study.

          -  primary graft failure is defined as:

               -  ANC < 500

               -  BM < 10% on two occasions (Day +21 and Day +28)

               -  Donor chimerism need not to be considered, provided there is no evidence of
                  malignancy

          -  secondary graft failure is defined as < 5% cellularity and ANC < 500 for more than 7
             days any time after primary engraftment).

               -  Women of childbearing potential must agree to use adequate contraception
                  (diaphragm, birth control pills, injections, intrauterine device [IUD], surgical
                  sterilization, subcutaneous implants, or abstinence, etc.) for the duration of
                  treatment.

               -  Patients or their guardian are able and willing to provide written informed
                  consent.

        Patient Exclusion Criteria:

        The presence of any of the following excludes a patient from study enrollment:

          -  Uncontrolled active infection defined as more than one week with no response to
             appropriately chosen antibiotics

          -  Evidence of recurrence of primary malignancy.

          -  Pregnant or lactating. The agents used in this study may be teratogenic to a fetus and
             there is no information on the excretion of agents into breast milk. All females of
             childbearing potential must have a blood test or urine study within 2 weeks prior to
             registration to rule out pregnancy. Women of childbearing age must use appropriate
             methods as described.

          -  Allergy to rituximab.

          -  Evidence of HIV infection or positive HIV serology.

          -  Autologous recovery defined as defined as greater than 90% recipient PCR product in
             the competitive VNTR PCR performed on gradually increasing white blood cell count.

        Donor Inclusion Criteria:

          -  Related donors must be 2-75 years of age and in good health.

          -  Meets match criteria

          -  Able and willing to undergo cell collection procedures (bone marrow cell collection or
             leukapheresis)

          -  Not pregnant or lactating.

          -  HIV-1, HIV-2 negative; HTLV-1, HTLV-2 negative, Hepatitis B and C negative.

          -  Patients or their guardian are able and willing to provide informed consent