Alemtuzumab and Combination Chemotherapy Followed By Donor Lymphocytes in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer
Condition: Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms
MeSH terms: Lymphoma; Leukemia; Preleukemia; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome
Study type: Interventional
Phase: Phase 1

Summary: 
      RATIONALE: Giving low doses of chemotherapy before a donor peripheral blood 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 system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving
      an infusion of the donor's T cells that have been treated in the laboratory after the
      transplant may help increase this effect. Sometimes the transplanted cells from a donor can
      also make an immune response against the body's normal cells. Giving tacrolimus before and
      after transplant may stop this from happening.

      PURPOSE: This phase I trial is studying the side effects and best dose of donor lymphocytes
      when given after alemtuzumab and combination chemotherapy in treating patients who are
      undergoing donor stem cell transplant for hematologic cancer.
    

Detailed description: 
      OBJECTIVES:

        -  Determine the feasibility and efficacy of a reduced-intensity conditioning regimen
           comprising alemtuzumab, fludarabine, melphalan, and thiotepa followed by allogeneic
           peripheral blood stem cell transplantation (PBSCT) in patients with hematologic
           malignancies.

        -  Determine the toxicity of this regimen in these patients.

        -  Determine the safety of LMB-2 immunotoxin-treated, selectively-depleted donor T cells,
           administered after allogeneic PBSCT, in these patients.

      OUTLINE: This is a dose-escalation study of LMB-2 immunotoxin-treated, selectively-depleted
      donor T cells.

        -  T cell preparation: Patients and donors undergo apheresis to obtain peripheral blood
           mononuclear cells (PBMCs), which are expanded in culture. Patients' PBMCs are irradiated
           and mixed with donor PBMCs. LMB-2 immunotoxin is added to the PBMCs in order to
           selectively deplete T cells from the donor PBMCs.

        -  Conditioning: Patients receive alemtuzumab IV over 2 hours on days -9 to -5, fludarabine
           IV over 30 minutes on days -8 to -5, melphalan IV over 15-20 minutes on day -4, and
           thiotepa IV on days -3 to -2.

        -  Immunosuppression: Patients receive tacrolimus IV continuously on days -10 to 1.

        -  Allogeneic peripheral blood stem cell (PBSC) transplantation: Patients undergo
           allogeneic PBSC transplantation on day 0.

        -  LMB-2 immunotoxin-treated, selectively-depleted donor T cells: Patients receive LMB-2
           immunotoxin-treated, selectively-depleted donor T cells IV over 30-60 minutes on
           approximately day 28.

      Cohorts of 3-6 patients receive escalating dose of LMB-2 immunotoxin-treated,
      selectively-depleted donor T cells until the maximum tolerated dose (MTD) is determined. The
      MTD is defined as the dose preceding that at which 2 of 6 patients experience
      dose-limiting-toxicity.

      After completion of study treatment, patients are followed weekly for 100 days
      post-transplantation and then periodically for survival.

      PROJECTED ACCRUAL: A total of 15-20 patients will be accrued for this study.
    

Intervention name(s): alemtuzumab; therapeutic allogeneic lymphocytes; fludarabine phosphate; melphalan; tacrolimus; thiotepa; peripheral blood stem cell transplantation
Intervention type(s): Biological; Biological; Drug; Drug; Drug; Drug; Procedure
Intervention MeSH terms: Fludarabine; Fludarabine phosphate; Melphalan; Alemtuzumab; Thiotepa; Tacrolimus
Primary purpose: Treatment
Keywords: accelerated phase chronic myelogenous leukemia; recurrent adult Burkitt lymphoma; stage IV adult Burkitt lymphoma; recurrent adult lymphoblastic lymphoma; stage IV adult lymphoblastic lymphoma; recurrent adult immunoblastic large cell lymphoma; stage IV adult immunoblastic large cell lymphoma; refractory anemia with excess blasts in transformation; refractory anemia with excess blasts; secondary myelodysplastic syndromes; chronic myelomonocytic leukemia; blastic phase chronic myelogenous leukemia; chronic eosinophilic leukemia; primary myelofibrosis; chronic neutrophilic leukemia; essential thrombocythemia; polycythemia vera; 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; refractory chronic lymphocytic leukemia; stage III chronic lymphocytic leukemia; stage IV chronic lymphocytic leukemia; stage III adult Burkitt lymphoma; stage III adult immunoblastic large cell lymphoma; stage III adult lymphoblastic lymphoma; myelodysplastic/myeloproliferative neoplasm, unclassifiable; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; atypical chronic myeloid leukemia, BCR-ABL1 negative