Melphalan, Fludarabine, and Alemtuzumab Followed by Peripheral Stem Cell Transplant in Treating Patients With Hematologic Cancer
Condition: Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms
MeSH terms: Lymphoma; Leukemia; Neoplasms; Multiple Myeloma; Neoplasms, Plasma Cell; Preleukemia; Plasmacytoma; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome
Intervention: alemtuzumab; cyclosporine; fludarabine phosphate; melphalan; allogeneic bone marrow transplantation; peripheral blood stem cell transplantation
Intervention description: Consenting individuals will receive pretransplant immunosuppressive cytoreduction, which will consist of 4 days of Campath-1H, 5 days of fludarabine, and two days of melphalan. All therapy should be completed approximately 24-36 hours before administration of the primary allograft.
Campath-1H (20mg/dose/day) will be administered for each of four days from day -8 to day -5, inclusive. Each dose will be infused intravenously over 8 hours.; Patients will be treated with Cyclosporine as prophylaxis against GvHD. Cyclosporine will be initiated at least 1 day prior to transplant at a dose of 1.5 mg / kg IV q12h (3 mg / kg / day = total daily dose). Dose will thereafter be adjusted to maintain a trough serum level of 200-300 ng /ml. Cyclosporine will be administered intravenously until the patient tolerates full alimentation, at which time conversion to oral dosing to sustain therapeutic levels will be initiated according to standard BMT service guidelines.; Fludarabine, 25mg/m2/d will be administered for each of five days from day -8 to day -4, inclusive. Each dose will be infused intravenously over 30 minutes.; Melphalan will be administered intravenously over 30 minutes on each of two days from day -3 to day -2, inclusive. The dose for recipients of HLA-matched related grafts will be 50 mg/m2/day x 2. The dose for recipients of HLA-matched unrelated and HLA-single allele disparate related or unrelated marrow or PBSC transplants will be 70 mg/m2/day x 2.
Intervention MeSH terms: Cyclosporine; Fludarabine; Fludarabine phosphate; Melphalan; Alemtuzumab; Cyclosporins
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 51.0
Sex: All
Maximum age: 70 Years
Healthy volunteers: No
Keywords: recurrent childhood acute lymphoblastic leukemia; recurrent adult Hodgkin lymphoma; refractory multiple myeloma; stage II multiple myeloma; stage III multiple myeloma; recurrent childhood lymphoblastic lymphoma; recurrent childhood acute myeloid leukemia; recurrent adult acute myeloid leukemia; recurrent adult acute lymphoblastic leukemia; relapsing chronic myelogenous leukemia; refractory chronic lymphocytic leukemia; recurrent/refractory childhood Hodgkin lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent grade 3 follicular lymphoma; recurrent adult diffuse small cleaved cell lymphoma; recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent adult lymphoblastic lymphoma; recurrent adult Burkitt lymphoma; previously treated myelodysplastic syndromes; recurrent childhood small noncleaved cell lymphoma; recurrent childhood large cell lymphoma; recurrent mantle cell lymphoma; Waldenström macroglobulinemia; childhood chronic myelogenous leukemia; atypical chronic myeloid leukemia, BCR-ABL1 negative; myelodysplastic/myeloproliferative neoplasm, unclassifiable; recurrent marginal zone lymphoma; recurrent small lymphocytic lymphoma; extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue; nodal marginal zone B-cell lymphoma; splenic marginal zone lymphoma; adult acute myeloid leukemia with 11q23 (MLL) abnormalities; childhood myelodysplastic syndromes

Summary:

      RATIONALE: Giving low doses of chemotherapy, such as melphalan and fludarabine, and a
      monoclonal antibody, such as alemtuzumab, before a donor bone marrow or 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). Sometimes the transplanted cells from a donor can also make an immune response
      against the body's normal cells. Giving cyclosporine after the transplant may stop this from
      happening.

      PURPOSE: This phase II trial is studying how well fludarabine, melphalan, alemtuzumab, and
      peripheral stem cell transplant work in treating patients with hematologic cancer.
    

Eligibility criteria:

        INCLUSION CRITERIA:

          -  Disease criteria: This trial is primarily designed for: 1) patients with relapsed or
             primary refractory non-Hodgkin's lymphoma, 2) chemosensitive relapsed or refractory
             acute and chronic lymphocytic leukemias, 3) relapsed or primary refractory Hodgkin's
             Disease, or advanced (Durie-Salmon stage II or III) multiple myeloma, advanced
             Waldenstrom macroglobulinemia, who, by virtue of advanced age, intensity of prior
             radiation and/or chemotherapy, history of prior toxicity associated with
             chemo/radiotherapy or existing organ dysfunction, would be at undue risk of regimen
             associated mortality if transplanted according to protocols involving myeloablative
             conditioning regimens.

          -  Patients with aggressive NHL histologies must have chemo/radiosensitive disease, or
             have non-progressive disease, or have stable disease on therapy, and be ineligible for
             an autologous HSC transplant because of disease in the marrow.

          -  Patients with chronic myeloid leukemia and high risk forms of acute myelogenous
             leukemia or myelodysplastic syndromes are also eligible in the absence of an
             alternative active higher priority allogeneic transplant protocol for which they are
             eligible.

          -  Age criteria: Patients may be up to 70 years of age. There is no lower age threshold.
             Patients above the age of 70 may also participate, after evaluation and approval by
             the BMT Service attendings.

          -  Absence of active or uncontrolled bacterial, viral, or fungal infection that would
             contraindicate the use of myelosuppressive chemotherapy.

          -  Patients must have a healthy HLA-compatible donor, either a matched or single HLA
             allele disparate related donor or a similarly compatible unrelated donor recruited
             through the National Marrow Donor Program. Related donors must be willing to
             participate as research subjects and be willing to receive G-CSF to mobilize PBPC and
             undergo leukapheresis to donate PBSC. Unrelated donors identified by the NMDP may
             elect to donate either PBSC after treatment with G-CSF, or bone marrow. These
             unrelated donors will provide informed consent and their PBSC or bone marrow donations
             will be obtained at a qualified donor center participating in the NMDP.

          -  Each patient must be willing to participate as a research subject and must sign an
             informed consent form after discussion of the nature and risks of the study prior to
             entering the protocol. Parents or legal guardians of patients who are minors will sign
             the consent form for these patients after discussion of the nature and risks of the
             study.

        EXCLUSION CRITERIA:

          -  Female patients who are pregnant or lactating.

          -  Active or uncontrolled viral (including HIV-1), bacterial or fungal infection.

          -  Severe renal insufficiency (creatinine >2.0 or creatinine clearance < 30mL/minute)

          -  Severe hepatic dysfunction, as defined by: total bilirubin greater than 2.5 mg/dL and
             AST and ALT >3xnl, unless the liver is involved with disease.

          -  Severe cardiac insufficiency, defined as a resting left ventricular ejection of less
             than 30% as measured by echocardiography or radionuclide cardiac angiography. Patients
             on cardiac medications for congestive heart failure are eligible, as long as their
             LVEF is greater than 30% on medication.

          -  Severe pulmonary insufficiency, as defined by an adjusted diffusing capacity of less
             than 40% of predicted value.

          -  Karnofsky or Lansky score <40%