Umbilical Cord Blood Transplantation Using a Myeloablative Preparative Regimen for Hematological Diseases
Umbilical Cord Blood Transplantation Using a Myeloablative Preparative Regimen for the Treatment of Hematological Diseases
Masonic Cancer Center, University of Minnesota
200 participants
Dec 1, 2016
INTERVENTIONAL
Conditions
Summary
This is a treatment guideline for an unrelated umbilical cord blood transplant (UCBT) using a myeloablative preparative regimen for the treatment of hematological diseases, including, but not limited to acute leukemias. The myeloablative preparative regimen will consist of cyclophosphamide (CY), fludarabine (FLU) and fractionated total body irradiation (TBI).
Eligibility
Inclusion Criteria18
- Eligible Disease Status
- Acute Myeloid Leukemia (AML): 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 recovery, AND \<5% blasts by light microscopy within the bone marrow with a 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 (ALL): high risk CR1 as defined by cytogenetics (such as t(9;22), t (1:19), t(4;11), other MLL rearrangements, hypodiploidy, or IKZF1 abnormalities), DNA index \< 0.81, \> 1 cycle to obtain CR or presence minimal residual disease (MRD). Patients in CR2+ are eligible. All patients must be in CR as defined by hematological recovery, AND \<5% blasts by light microscopy within the bone marrow with a cellularity of ≥15%.
- Very high risk pediatric patients with ALL: patients \<21 years are also considered high risk CR1 if they had M2 or M3 marrow at day 42 from the initiation of induction or M3 marrow at the end of induction. They are eligible once they achieved a complete remission.
- 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.
- Plasma Cell Leukemia after initial therapy, who achieved at least a partial remission
- Advanced Myelofibrosis
- 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 are eligible if there was disease progression/relapse within 12 of achieving a partial or complete remission. Patients who had remissions lasting \> 12 months, are eligible after at least two prior therapies. Patients with bulky disease (nodal mass greater than 5 cm) should be considered for de-bulking chemotherapy before transplant.
- Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia are eligible after initial therapy in CR1+ or PR1+.
- Large Cell NHL \> CR2/\> PR2: Patients in CR2/PR2 with initial short remission (\<6 months) are eligible.
- Lymphoblastic Lymphoma, Burkitt's Lymphoma, and other high-grade NHL after initial therapy if stage III/IV in CR1/PR1 or after progression if stage I/II \< 1 year.
- 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.
- Myeloproliferative Syndromes
- Availability of suitable UCB unit(s)
- to 55 years
- Voluntary written consent (adult or parental/guardian)
Exclusion Criteria6
- previous irradiation that precludes the safe administration of TBI - Radiation Oncology will evaluate all patients who have had previous radiation therapy
- chemotherapy refractory large cell and high grade NHL (ie progressive disease after \> 2 salvage regimens)
- if ≤ 18 years old, prior myeloablative transplant within the last 6 months. If \>18 years old prior myeloablative allotransplant or autologous transplant
- extensive prior therapy including \> 12 months alkylator therapy or \> 6 months alkylator therapy with extensive radiation
- pregnant or breastfeeding
- HIV positive
Interventions
25 mg/m\^2 IV of Fludarabine will be given over 1 hour on days -8, -7, and -6 pre-UCB transplant.
60 mg/kg IV of Cyclophosphamide will be given over 2 hours on days -7 and -6 pre-UCB transplant.
165 cGy of total body irradiation will be given twice a day on days -4, -3, -2, and -1.
Cyclosporine A (CSA) will start day -3 and will be administered PO/IV maintaining a trough level between 200 and 400 ng/mL. For adults the initial dose will be 2.5 mg/kg IV over 1 hour every 12 hours. For children \< 40 kg the initial dose will be 2.5 mg/kg IV over 1 hour every 8 hours.
Mycophenylate mofetil (MMF) 3 gram/day IV/PO for patients who are ≥ 40 kg divided in 2 or 3 doses. Pediatric patient (\<40 kilograms) will receive MMF at the dose of 15 mg/kg/dose every 8 hours beginning day -3.
Pre-medications and UCB infusion will be per current institutional policies/guidelines. The infusion of the first UCB unit should begin within 15 minutes, and no later than 30 minutes after arrival on the Unit. If 2 units are used, both cords will be infused within 30-60 minutes of each other as deemed clinically safe by the BMT attending or designee.
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT01962636