Allogeneic Hematopoietic Stem Cell Transplantation With Reduced Intensity Pre-transplant Conditioning for the Treatment of High-risk Hematological Malignancies (V3)
Condition: Hematological Malignancies
MeSH terms: Neoplasms; Hematologic Neoplasms
Intervention: Regimen A; Regimen B; Regimen C
Intervention description: Chronic Lymphocytic Leukemia/ Chronic Prolymphocytic Leukemia, Multiple Myeloma.; Other malignancies not addressed in A or C; B-Cell Lymphomas
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 78.0
Sex: All
Minimum age: 1 Year
Maximum age: 75 Years
Healthy volunteers: No
Keywords: high-risk hematological malignancies

Summary:

      This is study is for patients that have been diagnosed with high-risk hematological
      malignancies. The main purpose of this study is to confirm previously published results of
      stem cell transplantation with reduced intensity pre-transplant conditioning. Patients will
      be assigned to 1 of 3 regimens depending on the patient's diagnosis. Participants will be
      followed by the transplant team for the remainder of the patient's life. Patient's will visit
      MUSC daily, then visits will be reduced to frequent visits for up to 6 months. After 6
      months, the visits will be reduced more depending on the patient's condition.
    

Eligibility criteria:

        Inclusion Criteria:

          -  A proven diagnosis of one of the conditions in Table 1.

          -  Prior therapy including blood or marrow transplant will not exclude patients for
             reduced intensity transplant.

          -  Age < 75 years. Pediatric patients are eligible from the ages of 1 month to 18 years
             if the transplant physician believes that co-morbid conditions significantly increase
             the risk for a standard transplant regimen.

          -  HIV antibody negative.

          -  ECOG performance status 0-3, (or equivalent Karnofsky and Lansky performance scores
             for patients <18yrs, see appendix 2)

          -  Availability of an HLA-identical related donor or suitable alternative donor, (≥7/8
             allele match at A, B, C and DRB). Syngeneic transplants will not be allowed in this
             protocol.

          -  Due to the complexity of the study, all patients prior to enrollment will be assessed
             by the PI or co-PI.

          -  Patient with marrow failure states or immune deficiency syndromes undergoing stem cell
             transplants must be reviewed by one of the investigators to determine eligibility for
             study.

          -  Adequate insurance coverage (or financial resources) to cover the costs associated
             with the patient's transplant and, in the case of patients eligible for cohort C, to
             cover the costs associated with I 131 Tositumomab treatment.

        Exclusion Criteria:

          -  Active CNS involvement with malignant disease.

          -  Pregnancy.

          -  Fertile men or women unwilling to use contraceptive techniques during the study
             period.

          -  Creatinine clearance < 30 ml/min.

          -  Left ventricular ejection fraction <30% or clinical cardiac failure uncontrolled by
             medical therapy.

          -  Pulmonary disease requiring supplemental oxygen therapy.

          -  Patients with estimated life span less than 1 year due to medical illnesses other than
             the condition being treated on the study.

        Donor Selection:

        Inclusion Criteria

          -  Major HLA identical relative or genotypically matched unrelated donor (7-8/8 alleles)
             .

          -  Donors must meet the selection criteria as defined by the Foundation for the
             Accreditation of Cell Therapy (FACT) and will be screened per the American Association
             of Blood Banks (AABB) guidelines.

        Exclusion Criterion

          -  Positive anti-donor HLA antibody.

          -  Identical twin.