reduced intensity flu/mel/tbi conditioning for haplo hct patients with hematologic malignancies

Conditions: Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Biphenotypic Acute Leukemia; Undifferentiated Leukemia; Prolymphocytic Leukemia; Myelodysplastic Syndromes; Chronic Myelogenous Leukemia; Myeloproliferative Neoplasm; Relapsed Large Cell Lymphoma; Mantle Cell Lymphoma; Hodgkin Lymphoma; Burkitt Lymphoma; Relapsed T-Cell Lymphoma; Relapsed Chronic Lymphocytic Leukemia; Relapsed Small Lymphocytic Lymphoma; Relapsed Marginal B-cell Lymphoma; Relapsed Follicular Lymphoma; Lymphoplasmacytic Lymphoma

Summary: this is a single arm, phase ii trial of hla-haploidentical related hematopoietic cells transplant (haplo-hct) using reduced intensity conditioning (fludarabine and melphalan and total body irradiation). peripheral blood is the donor graft source. this study is designed to estimate disease-free survival (dfs) at 18 months post-transplant.


Eligibility criteria:
inclusion criteria: * age ≥ 55 years or hct co-morbidity score (hct-ci) \>/=3 * lack of a suitable 8/8 hla-matched sibling donor * adequate performance status is defined as karnofsky score ≥ 70% * patients and selected donor must be hla typed at high resolution using dna based typing at the following hla-loci: hla-a, -b, -c and drb1. donors must be hla-haploidentical relatives including, but not limited to, children, siblings, or parents, defined as having a shared hla haplotype between donor and patient at hla-a, -b, -c, and -drb1. * acute myeloid leukemia (aml): must be in remission with morphology (\<5% blasts) * acute lymphoblastic leukemia (all)/lymphoma second or greater complete remission (cr) first cr unable to tolerate consolidation chemotherapy due to chemotherapy-related toxicities, first cr high-risk all * biphenotypic/undifferentiated/prolymphocytic leukemias in first or subsequent cr * myelodysplastic syndrome: any subtype including refractory anemia (ra) if severe pancytopenia or complex cytogenetics. blasts must be less than 5%. if 5% of more requires chemotherapy for cytoreduction to \</=5% prior to transplantation. * chronic myelogenous leukemia in accelerated phase: patient must have failed at least two different tyrosine kinase inhibitor (tki)s, been intolerant to all tkis, or have t315l mutation * myeloproliferative neoplasms/myelofibrosis: blasts must be less than 5%. if 5% or more requires chemotherapy for cytoreduction to \</=5% prior to transplantation * relapsed large-cell lymphoma, mantle-cell lymphoma or hodgkin lymphoma that is chemotherapy sensitive and has failed or ineligible for an autologous transplant * burkitt's lymphoma in second cr or subsequent cr * relapsed t-cell lymphoma that is chemotherapy sensitive in cr/partial response (pr) that has failed or ineligible for an autologous transplant * natural killer cell malignancies * relapsed chronic lymphocytic leukemia/small lymphocytic lymphoma (cll/sll), marginal zone b-cell lymphoma, follicular lymphoma with any of the following: * progressed within 12 months of achieving a partial or complete remission patients who had remissions lasting up * patients who had remission lasting \> 12 months are eligible after at least two prior therapies * patients with primary, refractory disease. bulky disease and an estimated tumor doubling time of less than one month require debulking therapy prior to transplant. * lymphoplasmacytic lymphoma is eligible after initial therapy if chemotherapy sensitive * adequate organ function as defined per protocol * sexually active females of child bearing potential and males with partners of child bearing potential must agree to use adequate birth control during study treatment exclusion criteria: * pregnant or breastfeeding * untreated active infection * active hiv infection * prior allogenic transplant at any time prior or less than 6 months since prior autologous transplant (if applicable) * active central nervous system malignancy * favorable risk aml defined as per protocol * active central nervous system malignancy * favorable risk aml defined as having one of the following: * t(8,21) without ckit mutation or evidence of immunophenotypic, cytogenetic or molecular minimal residual disease (mrd) * inv(16) or t(16;16) without ckit mutation or evidence of mrd * normal karyotype with mutated npm1 but flt3-itd wild type without evidence of mrd * normal karyatype with double mutated cebpa without evidence of mrd