cryopreserved mmud bm with ptcy for hematologic malignancies

Conditions: Acute Leukemia; Myelodysplastic Syndromes; T-lymphoblastic Lymphoma; Acute Lymphocytic Leukemia; Acute Myeloid Leukemia; Acute Biphenotypic Leukemia; Acute Undifferentiated Leukemia

Summary: multicenter single arm study to assess the safety and efficacy of allogeneic transplantation using cryopreserved bone marrow from deceased mmud and ptcy, sirolimus and mmf for gvhd prophylaxis.


Eligibility criteria:
inclusion criteria: * provision of signed and dated informed consent form * stated willingness to comply with all study procedures and availability for the duration of the study * male or female, aged ≥ 18 and \< 71 years (note: hiv-negative subjects with mds must be aged \<50 at the time of signing the informed consent form) * diagnosed with * acute leukemias or t-lymphoblastic lymphoma (t-lbl) in 1st or subsequent cr * acute lymphocytic leukemia (all) or t-lbl as defined by the following: * \< 5% blasts in the bone marrow * normal maturation of all cellular components in the bone marrow * no currently active extramedullary disease (emd) (e.g., central nervous system (cns), soft tissue disease) * anc ≥ 1,000/mm3 * acute myeloid leukemia (aml) defined by the following: * \< 5% blasts in the bone marrow * no blasts with auer rods * normal maturation of all cellular components in the bone marrow * no currently active emd (e.g., cns, soft tissue disease) * anc ≥ 1,000/mm3 * acute biphenotypic leukemia (abl)/acute undifferentiated leukemia (aul) defined by the following: * \< 5% blasts in the bone marrow * normal maturation of all cellular components in the bone marrow * no currently active emd (e.g., cns, soft tissue disease) * anc ≥ 1,000/mm3 * myleodysplastic syndromes (mds), fulfilling the following criteria: * subjects with de novo mds who have or have previously had intermediate-2 or high-risk disease as determined by the ipss. current intermediate-2 or high- risk disease is not a requirement * subjects must have \< 20% bone marrow blasts, assessed within 60 days of informed consent * subjects may have received prior therapy for the treatment of mds prior to enrollment * performance status: karnofsky ≥ 60% * adequate organ function defined as: * cardiac: lvef at rest ≥ 35% (ric cohort) or lvef at rest ≥ 40% (fic cohort), or lvfs ≥ 25% * pulmonary: dlco, fev1, fvc ≥ 50% predicted by pulmonary function tests (pfts). dlco value may be corrected or uncorrected for hemoglobin * hepatic: total bilirubin ≤ 2.5 mg/dl, and alt, ast, and alp \< 5 x uln (unless alt, ast, and/or alp are disease related) * renal: scr within normal range for age (see table 5.1b). if scr is outside normal range for age, crcl \> 40 ml/min/1.73m2 must be obtained (measured by 24-hour (hr) urine specimen or nuclear glomerular filtration rate (gfr), or calculated gfr (by cockcroft-gault formula) * subjects must have the ability to give informed consent according to applicable regulatory and local institutional requirements * availability of deceased hla mmud cryopreserved product through ossium cryobank * hla mmud defined as 4-7/8 hla-allele matching at mhc class (a, b, or c) or mhc class ii (drb1) * additional mhc class ii hla (dp and dq) typing will be collected, but not incorporated in donor selection exclusion criteria: * pediatric patients (17 years or younger) * suitable hla-matched related or 8/8 allele matched (hla-a, -b, -c, -drb1) unrelated donor excluding ossium product * autologous hct \< 3 months prior to the time of signing the informed consent form * pregnancy or lactation * treatment with an investigational drug or other interventional gvhd clinical trials * current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings) * prior allogeneic hct * primary myelofibrosis or myelofibrosis secondary to essential thrombocythemia or polycythemia vera * subjects with mds may not receive ric and must be \< 50 years of age at the time of signing the informed consent form * any condition(s) or diagnosis, both physical or psychological, or physical exam finding that in the investigator's opinion precludes participation

Keywords: leukemia mds t-lbl all aml abl aul bone marrow transplant