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Adoptive TReg Cell for Suppression of aGVHD After UCB HSCT for Heme Malignancies

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ClinicalTrials.gov Identifier: NCT02991898
Recruitment Status : Suspended (Considering new technology for product.)
First Posted : December 14, 2016
Last Update Posted : September 6, 2018
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Tracking Information
First Submitted Date  ICMJE December 7, 2016
First Posted Date  ICMJE December 14, 2016
Last Update Posted Date September 6, 2018
Actual Study Start Date  ICMJE February 16, 2017
Estimated Primary Completion Date January 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 26, 2018)
Efficacy of Intervention [ Time Frame: 2 years ]
Measured by the length of Treg survival after infusion of Treg
Original Primary Outcome Measures  ICMJE
 (submitted: December 9, 2016)
Feasibility determined by the proportion of patients receiving the full course of IL-2 treatment [ Time Frame: 2 years ]
Change History Complete list of historical versions of study NCT02991898 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 7, 2018)
  • Grade II-IV aGVHD [ Time Frame: Assessed weekly until day 100, then day 180, 360 ]
    Probability of grade II-IV aGVHD
  • Grade III-IV aGVHD [ Time Frame: Assessed weekly until day 100, then day 180, 360 ]
    Probability of grade III-IV aGVHD
  • Treatment related mortality (TRM) [ Time Frame: 6 months ]
    Evaluated with descriptive statistics and plots or cumulative incidence curves if enough evaluable patients are available for time-to-event endpoints.
  • Relapse [ Time Frame: 1 year ]
    Evaluated with descriptive statistics and plots or cumulative incidence curves if enough evaluable patients are available for time-to-event endpoints.
  • Incidence of viral and fungal infections [ Time Frame: 1 year ]
    Evaluated with descriptive statistics and plots or cumulative incidence curves if enough evaluable patients are available for time-to-event endpoints.
  • Detectable Treg cells [ Time Frame: Day 14 ]
    The proportion of patients with detectable Treg cells at day 14 post infusion
  • Immune reconstitution [ Time Frame: Assessed at Day 4, weekly for 8 weeks ]
    The proportion of patients with immune reconstitution. Continuous endpoints will be described by medians, ranges and interquartile ranges as well as means and standard deviations if normally distributed.
  • Treg Cell Infusion Toxicity [ Time Frame: 48 hours post infusion ]
    Incidence of Adverse Events
  • Treg Survival [ Time Frame: 24 hours post infusion ]
    Length of Treg survival after infusion of Treg.
  • Chimerism [ Time Frame: Day +100 ]
    The incidence of chimerism in patients treated
  • Survival [ Time Frame: 1 year ]
    The probability of survival, one year post-treatment
  • Neutrophil Recovery [ Time Frame: Day 42 ]
    The incidence of neutrophil recovery in treated patients
  • Platelet Recovery [ Time Frame: 1 year ]
    The incidence of platelet recovery in treated patients
  • Chronic GVHD [ Time Frame: 1 year ]
    The incidence of chronic GVHD in treated patients after one year
Original Secondary Outcome Measures  ICMJE
 (submitted: December 9, 2016)
  • Grade II-IV aGVHD [ Time Frame: Assessed weekly until day 100, then day 180, 360, 720 ]
    Probability of grade II-IV aGVHD
  • Treatment related mortality (TRM) [ Time Frame: 6 months ]
  • Relapse [ Time Frame: 1 year ]
  • Incidence of viral and fungal infections [ Time Frame: 1 year ]
  • Detectable Treg cells [ Time Frame: Day 14 ]
    The proportion of patients with detectable Treg cells at day 14 post infusion
  • Immune reconstitution [ Time Frame: Assessed at Day 4, weekly for 8 weeks ]
  • Toxicity [ Time Frame: 48 hours post infusion ]
    Toxicity and adverse events will be classified according to NCI's Common Terminology Criteria for Adverse Events V 4.0 (CTCAE).
  • Treg Survival [ Time Frame: 24 hours post infusion ]
    Length of Treg survival after infusion of Treg.
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Adoptive TReg Cell for Suppression of aGVHD After UCB HSCT for Heme Malignancies
Official Title  ICMJE Adoptive Transfer of T Regulatory Cell for Suppression of Acute Graft-vs-Host-Disease After an Umbilical Cord Blood Transplant for Hematologic Malignancies
Brief Summary This is a single center pilot study of a non-myeloablative umbilical cord blood transplant for the treatment of a hematological malignancy with a single infusion of T regulatory (Treg) given shortly after UCB transplantation.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Lymphoblastic Leukemia
  • Burkitt Lymphoma
  • Natural Killer Cell Malignancies
  • Chronic Myelogenous Leukemia
  • Myelodysplastic Syndromes
  • Large-cell Lymphoma
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • Marginal Zone B-Cell Lymphoma
  • Follicular Lymphoma
  • Lymphoplasmacytic Lymphoma
  • Mantle-Cell Lymphoma
  • Prolymphocytic Leukemia
  • Hodgkin Lymphoma
  • Multiple Myeloma
  • Acute Myelogenous Leukemia
  • Biphenotypic Leukemia
  • Undifferentiated Leukemia
Intervention  ICMJE Biological: Infusion of Treg

Allopurinol on day -7 to day 0 Cyclophosphamide 50 mg/kg IV over 2 hours on day -6 Fludarabine 30mg/m2 IV over 1 hour on day -6, -5, -4, -3, and -2 Total Body Irradiation 200 cGy as a single dose

Sirolimus 8mg-12mg oral loading dose followed by signle dose 4mg/day. Levels are to be monitored 3 times/week in the first week, weekly until day +60, and as clinically indicated until day +100 post-transplantation.

Mycophenolate Mofetil (MMF) 3 gram/day IV/PO divided in 2 or 3 doses. Stop MMF at day +30 or 7 days after neutrophil recovery, whichever day is later, if no acute GVHD.

DUCBT followed Tregs - double umbilical cord blood transplant (FIRST) followed by the Treg cell infusion (SECOND) no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion.

Other Name: T regulatory cells
Study Arms Experimental: Treg Infusion
The Treg cell infusion is given no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion
Intervention: Biological: Infusion of Treg
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Suspended
Estimated Enrollment  ICMJE
 (submitted: December 9, 2016)
10
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date January 2025
Estimated Primary Completion Date January 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Must be ≥18, but < 70 years of age with no matched 7/8 or 8/8 sibling donor - patients ≥ 70 and ≤ 75 years of age may be eligible if they have a Co-Morbidity score ≤ 2 (http://www.qxmd.com/calculate-online/hematology/hct-ci)
  • UCB unit(s) composing the graft will be selected according to the current University of Minnesota umbilical cord blood graft selection algorithm and an additional cord blood unit to be used as the source to manufacture the Treg product. This UCB unit must be matched at 4-6/6 to the patient, considering HLA-A, B at the antigen level and DRB1 at the allele level
  • Acute Leukemias: Must be in remission by morphology. Also a small percentage of blasts that is equivocal between marrow regeneration versus early relapse are acceptable provided there are no associated cytogenetic markers consistent with relapse. Refer to Section 5.2 for complete definitions.
  • Burkitt's Lymphoma in CR2 or subsequent CR
  • Natural Killer Cell Malignancies
  • Chronic Myelogenous Leukemia: all types except refractory blast crisis. Chronic phase patients must have failed at least two different tyrosine-kinase inhibitors (TKIs), or been intolerant to all available TKIs or have T315I mutation.
  • Myelodysplastic Syndrome: IPSS INT-2 or High Risk; R-IPSS High or Very High; WHO classification: RAEB-1, RAEB-2; Severe Cytopenias: ANC < 0.8, Anemia or thrombocytopenia requiring transfusion; Poor or very poor risk cytogenetics based on IPSS or R-IPSS definitions; therapy-related MDS. Blasts must be be < 5%, preferably < 20% blasts by morphology by bone marrow aspirate morphology.. If ≥ 5% blasts, chemotherapy for cytoreduction to <5% blasts prior to transplantation may be considered.
  • Chronic myeloid neoplasms, inlcuding but not limited to CMML with blasts must around 5% blasts, preferably < 20% blasts by morphology by bone marrow aspirate morphology. If ≥5% blasts, chemotherapy for cytoreduction to <5% blasts prior to transplantation may be considered.
  • Large-Cell Lymphoma, Hodgkin Lymphoma and Multiple Myeloma with chemotherapy sensitive disease that has failed or patients who are ineligible for an autologous transplant.
  • Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL), Marginal Zone B-Cell Lymphoma, Follicular Lymphoma, which have progressed within 12 months 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 should be considered for debulking chemotherapy before transplant. Patients with refractory disease are eligible, unless has bulky disease and an estimated tumor doubling time of less than one month.
  • Lymphoplasmacytic Lymphoma, Mantle-Cell Lymphoma, Prolymphocytic Leukemia are eligible after initial therapy if chemotherapy sensitive.
  • Patients must have undergone an autologous transplant ≤ 12 months prior to transplant on this study or have received multi-agent or immunosuppressive chemotherapy within 3 months of the preparative regimen.

Performance Status, Organ Function, Contraception Use

  • Karnofsky score ≥ 70% (Appendix II)
  • Adequate organ function within 14 days (30 days for cardiac and pulmonary) of registration on-study defined as:

    • Renal: creatinine ≤ 2.0 mg/dL, for patient with a creatinine > 1.2 mg/dL or a history of renal dysfunction an estimated glomerular filtration rate ≥ 40 mL/min/1.73 m2 is required
    • ALT, AST and alkaline phosphatase ≤ 5 x upper limit of normal and total bilirubin ≤ 2.5 mg/dL except for patients with Gilbert's syndrome or hemolysis
    • Pulmonary function: DLCO, FEV1, FVC ≥ 40% predicted, and absence of O2 requirements.
    • Cardiac: Absence of decompensated congestive heart failure, or uncontrolled arrhythmia and left ventricular ejection fraction ≥ 40%.
  • Sexually active females of childbearing potential and males with partners of child-bearing potential must agree to use adequate birth control during study treatment.
  • Voluntary written consent

Exclusion Criteria:

  • Untreated active infection
  • 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 allogeneic transplantation
  • Less than 3 months from myeloablative conditioning for autologous transplantation (if applicable)
  • Evidence of progressive disease by imaging modalities or biopsy - persistent PET activity, though possibly related to lymphoma, is not an exclusion criterion in the absence of CT changes indicating progression.
  • CML in blast crisis
  • Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressing on salvage therapy.
  • Active central nervous system malignancy
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02991898
Other Study ID Numbers  ICMJE 2016LS107
MT2016-17 ( Other Identifier: University of Minnesota Blood and Marrow Transplant Program )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party Masonic Cancer Center, University of Minnesota
Study Sponsor  ICMJE Masonic Cancer Center, University of Minnesota
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Claudio Brunstein, MD, PhD Masonic Cancer Center, University of Minnesota
PRS Account Masonic Cancer Center, University of Minnesota
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP