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Inducible Regulatory T Cells (iTregs) in Non-Myeloablative Sibling Donor Peripheral Blood Stem Cell Transplantation

NCT01634217

Description:

This is a phase I single center dose escalation study with an extension at the best available dose to determine the tolerability of inducible regulatory T cells (iTregs) when given to adult patients undergoing non-myeloablative HLA-identical sibling donor peripheral blood stem cell (PBSC) transplantation for the treatment of a high risk malignancy. Up to 5 dose cohorts will be tested. Once the tolerable dose is determined for iTregs, enrollment will continue with an additional 10 patients using sirolimus/Mycophenolate mofetil (MMF) graft-versus-host disease (GVHD) prophylaxis to gain further safety information and to provide pilot data in this treatment setting.

Related Conditions:
  • Acute Lymphoblastic Leukemia
Recruiting Status:

Completed

Phase:

Phase 1

Trial Eligibility

Document

Inducible Regulatory T Cells (iTregs) in Non-Myeloablative Sibling Donor Peripheral Blood Stem Cell Transplantation

Title

  • Brief Title: Inducible Regulatory T Cells (iTregs) in Non-Myeloablative Sibling Donor Peripheral Blood Stem Cell Transplantation
  • Official Title: Dose Escalation Study With Extension of Inducible Regulatory T Cells (iTregs) in Adult Patients Undergoing Non-Myeloablative HLA Identical Sibling Donor Peripheral Blood Stem Cell Transplantation
  • Clinical Trial IDs

    NCT ID: NCT01634217

    ORG ID: 2012LS019

    NCI ID: MT2012-06R

    Trial Conditions

    Acute Myelogenous Leukemia

    Acute Lymphocytic Leukemia

    Chronic Myelogenous Leukemia

    Non-Hodgkin Lymphoma

    Hodgkin Lymphoma

    Chronic Lymphocytic Leukemia

    Multiple Myeloma

    Myelodysplastic Syndrome

    Trial Interventions

    Drug Synonyms Arms

    Trial Purpose

    This is a phase I single center dose escalation study with an extension at the best
    available dose to determine the tolerability of inducible regulatory T cells (iTregs) when
    given to adult patients undergoing non-myeloablative HLA-identical sibling donor peripheral
    blood stem cell (PBSC) transplantation for the treatment of a high risk malignancy. Up to 5
    dose cohorts will be tested. Once the tolerable dose is determined for iTregs, enrollment
    will continue with an additional 10 patients using sirolimus/Mycophenolate mofetil (MMF)
    graft-versus-host disease (GVHD) prophylaxis to gain further safety information and to
    provide pilot data in this treatment setting.

    Detailed Description

    Co-enrollment in University Of Minnesota protocol MT2001-10 is required and transplantation
    will be according to that protocol with iTregs administered the morning of day 0 followed no
    sooner than 4 hours later by the PBSC transplantation.

    Trial Arms

    Name Type Description Interventions
    Cohort 1 Experimental Administered 3 x 10^6 iTregs/kg infusion
    Cohort 2 Experimental Administered 3 x 10^7 iTregs/kg infusion
    Cohort 3 Experimental Administered 3 x 10^8 iTregs/kg infusion
    Cohort 4 Experimental Administered 10 x 10^8 iTregs/kg infusion
    Cohort 5 Extension Experimental Administered 10 x 10^8 iTregs/kg or best available dose using sirolimus/MMF as graft-versus-host disease (GVHD) prophylaxis. Immunosuppression will consist of a combination of sirolimus and mycophenolate mofetil (MMF). Sirolimus will be administered starting at day -3 with 8mg-12mg oral loading dose followed by single dose 4 mg/day. MMF will be administered starting on day -3 at a dose of 3 gram/day divided in 2 or 3 doses. Intravenous (IV) route between days -3 and +5, then may change to PO between days +6 and +30. Stop MMF at day +30 or 7 days after engraftment, whichever day is later, if no acute GVHD.

    Eligibility Criteria

    Inclusion Criteria:

    - 18 - 75 years of age with an HLA-identical sibling donor

    - One of the following disease categories:

    - Acute myelogenous leukemia - high risk CR1 (as evidenced by preceding MDS,
    intermediate to high risk cytogenetics, 2 cycles to obtain CR, erythroblastic
    or megakaryocytic leukemia; CR2+. All patients must be in CR as defined by
    hematological recovery (ANC > 0.5x 109/L), AND <5% blasts by light microscopy
    within the bone marrow with a cellularity of 15%.

    - Acute lymphocytic leukemia - high risk CR1 [t(9;22), t (1:19), t(4;11) or other
    MLL rearrangements] or >1cycle to obtain CR; CR2+. All patients must be in CR as
    defined by hematological recovery (ANC > 0.5x 109/L), AND <5% blasts by light
    microscopy within the bone marrow with a cellularity of 15%.

    - Chronic myelogenous leukemia all types except blast crisis (note treated blast
    crisis in chronic phase is eligible)

    - Non-Hodgkin lymphoma or Hodgkin lymphoma demonstrating chemosensitive disease

    - Myelodysplastic syndrome with severe pancytopenia, leading to either transfusion
    dependency or increased risk for infections

    - Performance status: Karnofsky 60%

    - Adequate organ function within 28 days of study enrollment defined as:

    - Liver: SGOT and SGPT < 5.0 x ULN; total bilirubin < 3 x ULN

    - Renal: serum creatinine < 2.0 mg/dl or glomerular filtration rate (GFR) > 40
    mL/min/1.73m2. Patients with a creatinine > 1.2 mg/dl or a history of renal
    dysfunction must have glomerular filtration rate (GFR) > 40 mL/min/1.73m2

    - Albumin: > 2.5 g/dL

    - Cardiac: No decompensated CHF or uncontrolled arrhythmia; ejection fraction >
    35% within 6 weeks prior to study enrollment

    - Pulmonary: No O2 requirements; DLCO > 30% predicted within 6 weeks prior to
    study enrollment

    - If recent mold infection (e.g. aspergillus) must have minimum of 30 days of therapy
    and responsive disease and be cleared by Infectious Disease

    - Sexually active females of child bearing potential and males must agree to use
    effective contraception for the duration of the transplant period

    - Voluntary written consent

    Exclusion Criteria:

    - Pregnancy or breast feeding - women of childbearing potential must have a negative
    pregnancy test within 28 days of study enrollment.

    - Prior myeloablative transplant within previous 3 months of study enrollment.

    - Evidence of HIV infection or known HIV positive serology.

    - Active serious infection.

    Minimum Eligible Age: 18 Years

    Maximum Eligible Age: 75 Years

    Eligible Gender: Both

    Primary Outcome Measures

    Incidence of grade 3-5 infusional toxicity

    Secondary Outcome Measures

    Cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD)

    Incidence of chronic graft-versus-host disease (GVHD)

    Relapse of Disease

    Survival

    Survival

    Trial Keywords