Title A Phase I Trial to Determine Safety and Tolerability of Ex Vivo Expanded Human Myeloid Progenitor Cells (CLT-008) Infused 24 Hours Post Transplant to Support Allogeneic Umbilical Cord Blood Transplantation for Hematologic Malignancies
IRB CLNT 1Z09
Hospital Main Campus
Phase Phase 1
Disease Blood & Marrow Transplant (BMT), Hematologic Malignancy, Leukemia, Acute Lymphoblastic (ALL) , Leukemia, Chronic Lymphocytic (CLL), Leukemia, Chronic Myeloid (CML), Lymphoma, Lymphoma, Non - Hodgkin, Multiple Myeloma, Myelodysplastic Syndrome (MDS)
Drug Ex Vivo
- Determine safety and tolerability of single-donor and pooled-donor ex vivo expanded human myeloid progenitor cells (CLT-008) when administered 24 hours after a UCB transplant
- Patients aged 12 to 65 years (inclusive) scheduled to undergo UCB transplant with HLA 4-6/6 matched umbilical cord blood graft containing ≥ 2.5 x 107 nucleated cells/kilogram (cryopreserved) with a hematological malignancy as described below will be considered for participation:
- Acute myeloid leukemia: high risk CR1 (as evidenced by preceding MDS, high risk cytogenetics, ≥ 2 cycles to obtain CR, erythroblastic or megakaryocytic leukemia; CR2+. All patients must be in CR as defined by hematological criteria e.g. < 5% blasts by light microscopy with a marrow cellularity of ≥15%.
- Very high risk pediatric patients with AML. Patients <21 years, however, are eligible with (M2 marrow) with < 25% blasts in marrow after having failed one or more cycles of chemotherapy.
- Acute lymphocytic leukemia: high risk CR1 [t(9;22), t (1:19), t(4;11) or other MLL rearrangements] or > 1 cycle to obtain CR; CR2+. All patients must be in CR as defined by hematological recovery, e.g. <5% blasts by light microscopy with a marrow cellularity of ≥15%.
- Chronic myelogenous leukemia excluding refractory blast crisis. To be eligible in first chronic phase (CP1) patient must have failed or be intolerant to imatinib mesylate or in accelerated phase or in second chronic phase.
- Myelodysplasia (MDS) IPSS Int-2 or High risk (i.e. RAEB, RAEBt) or refractory anemia with severe pancytopenia or high risk cytogenetics. Blasts must be < 10% by a representative bone marrow aspirate morphology.
- Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma or follicular lymphoma that have progressed after at least two prior therapies. Patients with bulky disease (nodal mass greater than 5 cm) should be considered for debulking chemotherapy before transplant.
- Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy in CR1+ or PR1+.
- Large cell non Hodgkin lymphoma (NHL) in > CR2 or > PR2. Patients in CR2 or PR2 with initial short remission (< 6 months) are eligible. Chemotherapy refractory large cell NHL (ie progressive disease after > 2 salvage regimens) is NOT eligible.
- Lymphoblastic lymphoma, Burkitt's lymphoma, and other high-grade NHL after initial therapy if stage III/IV in CR1 or PR1 or after progression if stage I/II < 1 year. Chemotherapy refractory high grade NHL (ie progressive disease after > 2 salvage regimens) is NOT eligible.
- Multiple myeloma beyond PR2. Patients with chromosome 13 abnormalities, first response lasting less than 6 months, or β-2 microglobulin > 3 mg/L, may be considered for this protocol after initial therapy.
- Performance Status and Organ Function: Recipients must have a Karnofsky score (adults) ≥ 80 % or Lansky score ≥ 50% (pediatrics) (appendix II) and have acceptable organ function defined as:
- Renal: creatinine ≤ 1.6 mg/dL
- Hepatic: bilirubin, AST/ALT, ALP < 2 x upper limit of normal,
- Pulmonary function: DLCOcorr > 50% normal,
- Cardiac: left ventricular ejection fraction > 45%.
- Pre-transplant Preparative Regimen: Scheduled to undergo preparative regimen of the following prior to UCB transplant:
- Cyclophosphamide 60 mg/kg IV x 2 days (Days -7 and -6),
- Fludarabine 25 mg/m2 IV x 3 days (Days -8, -7, -6), and
- TBI 1200-1320 cGy in eight fractions (Days -4, -3, -2, -1)
- Symptomatic underlying pulmonary disease (regardless of corrected DLCO) or requiring supplemental oxygen
- Active infection at time of transplantation (including active infection with Aspergillus or other mold within 30 days.)
- Evidence of HIV infection or known HIV positive serology
- Pregnant or breast feeding. The agents used in the preparative regimen are teratogenic to a fetus and there is no information on the excretion of agents into breast milk. Females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy
- If ≤ 18 years old, prior myeloablative transplant within the last 6 months. If > 18 years old prior myeloablative allotransplant or autologous transplant
- Extensive prior chemotherapy and radiotherapy including > 12 months alkylator therapy or > 6 months alkylator therapy with extensive radiation.
- Patients who have received Y-90 ibritumomab (Zevalin) or I-131 tositumomab (Bexxar)) as part of their salvage therapy
- Patients who have an available HLA identical sibling hematopoietic stem cell donor
- Uncontrolled medical condition considered high-risk for investigational new drug treatment