Reduced-intensity, Related-donor Bone Marrow Transplantation Followed by High-dose Cyclophosphamide for Hematologic Cancers
Condition: Lymphoma; Leukemia; Myelodysplastic Syndrome
MeSH terms: Lymphoma; Leukemia; Preleukemia; Myelodysplastic Syndromes
Intervention: Fludarabine; Busulfan; Cyclophosphamide; Mycophenolate Mofetil; Tacrolimus
Intervention description: 30 mg/m^2 IV daily on Day -6 through Day -2.; 1 mg/kg PO OR 0.8 mg/kg IV four times daily on Day -6 through Day -3.; 50 mg/kg IV daily on Day +3 and Day +4.; 15 mg/kg PO three times daily (max daily dose of 3g) starting on Day +5.; Dosed based on drug levels; begin on Day +5 at 1 mg IV daily.
Intervention MeSH terms: Mycophenolic Acid; Cyclophosphamide; Busulfan; Fludarabine; Tacrolimus
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 6 Months
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Lymphoma; Hodgkin's lymphoma; Non hodgkin's lymphoma; Leukemia; Acute myeloid leukemia (AML); Acute lymphoblastic leukemia(ALL); Chronic myeloid leukemia (CML); Chronic Myelomonocytic (CMML); Myelodysplastic syndrome (MDS); High-risk acute leukemia in first remission; Relapsed leukemia in remission; Cyclophosphamide; High-dose cyclophosphamide; Fludarabine; Busulfan; Allogeneic; Nonmyeloablative; Reduced intensity; Haploidentical; Bone marrow transplant (BMT)

Summary:

      This research is being done to learn more about reduced-intensity bone marrow transplantation
      (BMT), also known as a "mini" transplant for patients with blood cancers, using bone marrow
      from a relative.

      The main goal of the study is to determine how quickly the donor's bone marrow "takes" in
      your body. Other goals include describing how many people accept the bone marrow and how
      quickly the blood counts come up; describing Graft-versus-host disease (GVHD) and other
      complications; and describing how many people survive without progressive cancer and survive
      overall
    

Eligibility criteria:

        Inclusion Criteria:

          -  First-degree related donor who is at minimum HLA haploidentical

          -  Eligible diagnoses:

               1. Low-grade non-Hodgkin's lymphoma or plasma cell neoplasm that has progressed
                  during multiagent therapy, failed at least two prior therapies (excluding single
                  agent rituximab and single agent steroids), or in the case of lymphoma undergone
                  histological conversion:

                    -  Follicular grade 1 or 2 lymphoma

                    -  Follicular lymphoma not otherwise specified

                    -  Marginal zone (or MALT) lymphoma

                    -  Lymphoplasmacytic lymphoma / Waldenstrom's macroglobulinemia

                    -  Hairy cell leukemia

                    -  Small lymphocytic lymphoma (SLL) or chronic lymphocytic leukemia (CLL)

                    -  Prolymphocytic leukemia

                    -  Low grade B-cell lymphoma, unspecified

                    -  Multiple myeloma

                    -  Plasma cell leukemia

               2. Poor-risk SLL or CLL, defined by an 11q or 17p deletion, histological conversion,
                  or disease progression < 6 months after a purine analog-containing regimen

               3. Aggressive lymphoma that has failed at least one prior regimen of multiagent
                  chemotherapy, and patient is either ineligible for autologous BMT or autologous
                  BMT is not recommended:

                    -  Hodgkin lymphoma

                    -  Follicular grade 3 lymphoma

                    -  Mantle cell lymphoma or leukemia

                    -  Diffuse large B-cell lymphoma (excluding primary CNS lymphoma). Eligible
                       subtypes include primary mediastinal large B-cell lymphoma, T-cell rich
                       large B-cell lymphoma, and large B-cell lymphoma not otherwise specified.

                    -  Burkitt's lymphoma/leukemia

                    -  Atypical Burkitt's lymphoma/leukemia (high grade B-cell lymphoma,
                       unclassified, including that with features intermediate between Burkitt's
                       and diffuse large B-cell lymphoma)

                    -  Anaplastic large cell lymphoma

                    -  Plasmablastic lymphoma

                    -  Peripheral T-cell lymphoma

               4. Relapsed or refractory acute leukemia in second or subsequent remission

               5. Poor-risk acute leukemia in first remission

               6. AML with at least one of the following:

                    -  AML arising from MDS or a myeloproliferative disorder, or secondary AML

                    -  Presence of Flt3 internal tandem duplications

                    -  Poor-risk cytogenetics

                    -  Primary refractory disease

                         -  ALL (leukemia and/or lymphoma) with at least one of the following:

                    -  Adverse cytogenetics

                    -  Clear evidence of hypodiploidy

                    -  Primary refractory disease

                         -  Biphenotypic leukemia

                         -  MDS with at least one of the following features:

                         -  Poor-risk cytogenetics

                         -  IPSS score of INT-2 or greater

                         -  Treatment-related MDS

                         -  MDS diagnosed before age 21 years

                         -  Progression on or lack of response to standard DNA-methyltransferase
                            inhibitor therapy

                         -  Life-threatening cytopenias, including those generally requiring
                            greater than weekly transfusions

               7. Interferon- or imatinib-refractory CML in first chronic phase, or non-blast
                  crisis CML beyond first chronic phase

               8. Philadelphia chromosome negative myeloproliferative disease (including
                  myelofibrosis)

               9. Chronic myelomonocytic leukemia

              10. Juvenile myelomonocytic leukemia

                    -  For patients with SLL, CLL, or prolymphocytic leukemia, < 20% of bone marrow
                       cellularity involved by this process

                    -  Adequate end-organ function:

          -  Left ventricular ejection fraction greater than or equal to 35%

          -  Bilirubin ≤ 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis), and ALT and AST
             < 5 x ULN

          -  FEV1 and FVC > 40% of predicted; or in pediatric patients, if unable to perform
             pulmonary function tests due to young age, oxygen saturation >92% on room air

               -  ECOG performance status < 2 or Karnofsky or Lansky score > 60

        Exclusion Criteria:

          -  Pregnant or breast-feeding

          -  Uncontrolled infection Note: Infection is permitted if there is evidence of response
             to medication. Eligibility of HIV infected patients will be determined on a
             case-by-case basis.

          -  Any previous BMT within 3 months prior to start of conditioning

          -  Active extra-medullary leukemia or known active Central Nervous System (CNS)
             involvement by malignancy. Such disease treated into remission is permitted.