Pentostatin and Alemtuzumab as a Preparative Regimen for Allogeneic Peripheral Blood Stem Cell Transplantation
Condition: Leukemia; Lymphoma; Hodgkin's Disease; Hematologic Neoplasms; Multiple Myeloma; Carcinoma, Renal Cell
MeSH terms: Leukemia; Multiple Myeloma; Hodgkin Disease; Carcinoma, Renal Cell; Hematologic Neoplasms
Intervention: Pentostatin; Alemtuzumab; Allogeneic hematopoietic stem cell transplantation
Intervention description: Days - 8 through -6: pentostatin 4 mg/m2/24 hr as a continuous intravenous infusion (CIVI) (total cumulative dose, 12 mg/m2 over 3 days); Days - 5 through - 1: alemtuzumab 20 mg per dose intravenously over 8 hours daily for 5 doses (total cumulative dose, 100 mg); Infusion of related or unrelated donor peripheral blood progenitor cells on day 0.
Intervention MeSH terms: Alemtuzumab; Pentostatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Allogeneic Hematopoietic Cell Transplantation; Preparative Regimen; Pentostatin; Alemtuzumab; Hodgkin Disease and Lymphoma, non-Hodgkin; leukemia, myeloid, acute; leukemia, lymphocytic, acute; leukemia, myeloid, chronic; leukemia, lymphocytic, chronic; Multiple Myeloma; Myelodysplastic Syndromes; Carcinoma, Renal Cell

Summary:

      This study tests the hypothesis that a purely immunosuppressive preparative regimen allows
      engraftment of related or unrelated allogeneic hematopoietic stem cells in subjects with
      high-risk malignancies, without causing the post-transplant myelosuppression (e.g.,
      neutropenia, thrombocytopenia) that occurs with currently used reduced-intensity
      (nonmyeloablative) preparative regimens. This study incorporates both safety and efficacy
      endpoints and evaluates a novel preparative regimen of alemtuzumab plus continuous-infusion
      pentostatin, two immunosuppressive agents with different mechanisms of action, in recipients
      of related or unrelated allogeneic hematopoietic stem cell transplantation.
    

Eligibility criteria:

        Inclusion Criteria:

        One of these diagnoses:

          -  Acute myeloid leukemia in complete or partial remission

          -  Acute lymphocytic leukemia in complete or partial remission

          -  Chronic myeloid leukemia in first or subsequent chronic phase or accelerated phase

          -  Chronic lymphocytic leukemia that has recurred or failed after at least one course of
             front-line therapy

          -  Hodgkin's disease or non-Hodgkin's lymphoma that has failed front-line therapy, is in
             second or subsequent remission, or is in chemosensitive relapse

          -  Multiple myeloma that is in complete or partial remission or in chemosensitive relapse

          -  Myelodysplastic Syndrome classified as intermediate-2 or high risk according to
             International Prognostic Scoring System

          -  Metastatic renal cell carcinoma that has failed at least one previous front-line
             chemotherapy and/or biological therapy regimen and that is radiographically detectable
             and evaluable

          -  Treatment with at least one previous course of chemotherapy or biological therapy for
             the malignancy for which allogeneic PBPCT is being considered (i.e., a subject cannot
             be enrolled on this study for initial treatment of a malignancy).

        AND at least one of the following:

          -  Age 50 years or older.

          -  Previous transplant with autologous or allogeneic hematopoietic cells (peripheral
             blood, bone marrow, or placental blood).

          -  High-risk status of hematologic malignancy, i.e., not in first complete remission or
             first chronic phase.

          -  Presence of other medical condition that could place subject at unacceptably high risk
             of regimen-related mortality such as documented chronic bronchitis or emphysema;
             decreased cardiac ejection fraction (but with ejection fraction at least 30%), or
             history of coronary artery disease; renal insufficiency (but with creatinine clearance
             at least 30 mL/min); hepatic cirrhosis (but with normal hepatic synthetic function);
             or documented or presumed invasive fungal infection requiring treatment with
             intravenous antifungal agent(s).

        Exclusion Criteria:

          -  Eligibility for another clinical therapeutic protocol or standard-of-care treatment
             that offers higher probability of cure or long-term control of subject's malignancy.

          -  Progressive Hodgkin's disease, non-Hodgkin's lymphoma, Hodgkin disease or multiple
             myeloma that is refractory to salvage chemotherapy.

          -  Acute leukemia (AML or ALL) in relapse, CML in blast phase/blast crisis, or MDS with
             greater than 30% marrow involvement (MDS-AML). Subjects with these disease
             characteristics may be considered for this study if complete or partial remissions
             (CRs or PRs) occur after salvage chemotherapy.

          -  Severe organ dysfunction, such as: cardiac ejection fraction below 30% or symptomatic
             ischemic cardiac disease; creatinine clearance below 30 mL/min; carbon monoxide
             diffusing capacity (DLCO) below 35% and/or need for supplemental oxygen; severe
             hepatic cirrhosis with ascites and/or varices; hepatic dysfunction associated with
             abnormal synthetic function (e.g., coagulopathy) and/or bilirubin greater than two
             times upper limit of normal and/or transaminases (AST or ALT) above four times upper
             limit of normal.

          -  Untreated or progressive central nervous system involvement by malignancy

          -  Subject is pregnant or breast-feeding.

          -  Karnofsky score below 50

          -  Seropositivity for human immunodeficiency virus (HIV).

          -  Life expectancy less than 12 weeks with conventional treatments.

          -  For subjects who are fertile, refusal to practice contraception upon entering this
             study and for at least 12 months after PBPCT or after cessation of immunosuppressive
             treatments (e.g., cyclosporine), whichever occurs later.

          -  Failure to obtain at least 5.0 x 106 allogeneic donor CD34+ cells per kg of recipient
             weight in PBPC product.