Status:

WITHDRAWN

T-Regulatory Cell and CD3 Depleted Double Umbilical Cord Blood Transplantation in Hematologic Malignancies

Lead Sponsor:

Masonic Cancer Center, University of Minnesota

Conditions:

Hematologic Malignancy

Acute Myeloid Leukemia

Eligibility:

All Genders

18-55 years

Phase:

PHASE1

PHASE2

Brief Summary

This is a unique dose-escalation trial that will titrate doses of umbilical cord blood (UCB) Treg and CD3+ Teff cells with the goal of infusing as many CD3+ Teff cells as possible without conferring g...

Detailed Description

Based on prior studies, the first patient will start at lowest dose combination (3 x 10\^6/kg of Treg and 3 x 10\^6/kg of CD3+ Teff cells). One patient will be entered at each level with a minimum of...

Eligibility Criteria

Inclusion

  • Only patients requiring a double umbilical cord blood (UCB) transplant are to be considered for this study.
  • UCB Requirements
  • Three UCB units are required - one for Treg production and two for UCB transplant. The unrelated UCB donors must be 4-6/6 HLA-A, B, DRB1 matched with the recipient (HLA matching using molecular techniques: A and B to antigen level resolution and DR to allele level resolution). Suitable UCB units will be selected according to the University Of Minnesota UCB Graft Selection Algorithm.
  • Suitable UCB units must be ABO matched.
  • Disease Criteria:
  • Patients aged 18 to 55 years
  • Acute Myeloid Leukemia: with morphologically persistent disease in a representative bone marrow aspirate sample with ≤ 10% blasts after at least 1 cycles of chemotherapy (if patient refuses or is disqualified from alternative protocols), or in 3rd or higher complete remission (CR).
  • Acute Lymphocytic Leukemia: with morphologically persistent disease in a representative bone marrow aspirate sample with ≤ 10% blasts after at least 1 cycles of chemotherapy, or in 3rd or higher CR
  • Chronic Myelogenous Leukemia in Blast Crisis: with ≤10% residual blasts in the bone marrow aspirate after at least 1 cycle of induction chemotherapy in combination with a tyrosine kinase inhibitor (TKI)
  • Refractory Anemia with Excess Blasts: (≤ 10%) in representative bone marrow aspirate sample of blasts after 1 cycle of induction chemotherapy. If treated with hypomethylating agents, patients are eligible if blast count is ≤ 10% after 4 cycles or evidence of stable or progressive disease after at least 2 cycles.
  • Chronic Myeloproliferative Disease
  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Marginal Zone B-Cell Lymphoma or Follicular Lymphoma: disease must be refractory after at least two chemotherapy regimens or is chemotherapy sensitive but has residual nodal disease of ≥ 5 cm
  • Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia: disease must be refractory after at least two chemotherapy regimens or is chemotherapy sensitive but has residual nodal disease of ≥ 5 cm
  • Large Cell Non-Hodgkin's Lymphoma: disease must be refractory after at least two chemotherapy regimens or is chemotherapy sensitive but has residual nodal disease of ≥ 5 cm
  • Lymphoblastic Lymphoma, Burkitt's Lymphoma, and other High-Grade NHL: disease must be refractory after at least two chemotherapy regimens or is chemotherapy sensitive but has residual nodal disease of ≥ 5 cm
  • Performance Status, Age, and Organ Function
  • Adequate performance status defined as a Karnofsky score ≥ 80%
  • Adequate organ function defined as:
  • Renal: creatinine \< 2.0 mg/dL,
  • Hepatic: bilirubin, AST/ALT, ALP \< 5 x upper limit of normal,
  • Pulmonary function: DLCOcorr \> 50% normal,
  • Cardiac: left ventricular ejection fraction \> 45%
  • Voluntary written informed consent signed before performance of any study-related procedure not part of normal medical care

Exclusion

  • Available medically suitable HLA-identical related donor
  • Active infection at time of transplantation (including active infection with Aspergillus or other mold within 30 days)
  • History of HIV infection
  • Pregnant or breast feeding. The agents used in this study may be 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 14 days prior to registration to rule out pregnancy
  • Prior myeloablative transplant within the last 6 months
  • Extensive prior therapy 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 (not eligible for myeloablative umbilical cord blood transplant)

Key Trial Info

Start Date :

January 1 2014

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

January 1 2015

Estimated Enrollment :

Patients enrolled

Trial Details

Trial ID

NCT01163201

Start Date

January 1 2014

End Date

January 1 2015

Last Update

December 2 2017

Active Locations (1)

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Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States, 55445