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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT02991898
Other study ID # 2016LS107
Secondary ID MT2016-17
Status Terminated
Phase Phase 2
First received
Last updated
Start date February 16, 2017
Est. completion date June 20, 2019

Study information

Verified date September 2020
Source Masonic Cancer Center, University of Minnesota
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Terminated
Enrollment 3
Est. completion date June 20, 2019
Est. primary completion date June 20, 2019
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility 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, including 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

Study Design


Related Conditions & MeSH terms

  • Acute Lymphoblastic Leukemia
  • Acute Myelogenous Leukemia
  • Biphenotypic Leukemia
  • Burkitt Lymphoma
  • Chronic Lymphocytic Leukemia
  • Chronic Myelogenous Leukemia
  • Follicular Lymphoma
  • Hodgkin Lymphoma
  • Large-cell Lymphoma
  • Leukemia
  • Leukemia, Lymphocytic, Chronic, B-Cell
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukemia, Myeloid
  • Leukemia, Myeloid, Acute
  • Leukemia, Prolymphocytic
  • Lymphoma
  • Lymphoma, B-Cell, Marginal Zone
  • Lymphoma, Mantle-Cell
  • Lymphoplasmacytic Lymphoma
  • Mantle-Cell Lymphoma
  • Marginal Zone B-Cell Lymphoma
  • Multiple Myeloma
  • Myelodysplastic Syndromes
  • Natural Killer Cell Malignancies
  • Neoplasms
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Prolymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • Undifferentiated Leukemia
  • Waldenstrom Macroglobulinemia

Intervention

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 single 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.

Locations

Country Name City State
United States Masonic Cancer Center at University of Minnesota Minneapolis Minnesota

Sponsors (1)

Lead Sponsor Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Participants Survived Count of patients who survived 2 years post intervention 2 years
Secondary Number of Participants With Grade II-IV aGVHD Probability of grade II-IV aGVHD Assessed weekly until day 100, then day 180, 360
Secondary Number of Participants Experiencing Treatment Related Mortality (TRM) Evaluated with descriptive statistics and plots or cumulative incidence curves if enough evaluable patients are available for time-to-event endpoints. 6 months
Secondary Number of Participants Who Experienced Relapse Evaluated with descriptive statistics and plots or cumulative incidence curves if enough evaluable patients are available for time-to-event endpoints. 1 year
Secondary Number of Participants With Incidence of Bacterial, Viral and Fungal Infections Evaluated with descriptive statistics and plots or cumulative incidence curves if enough evaluable patients are available for time-to-event endpoints. 1 year
Secondary Number of Participant With Detectable Treg Cells at d14 The proportion of patients with detectable Treg cells at day 14 post infusion 14 days
Secondary Number of Participants With Immune Reconstitution 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. Assessed at Day 4, weekly for 8 weeks
Secondary Number of Participants Experiencing Treg Cell Infusion Toxicity Incidence of Adverse Events 48 hours post infusion
Secondary Length of Treg Survival Length of Treg survival after infusion of Treg. 24 hours post infusion
Secondary Percentage of Donor Cell Chimerism The incidence of chimerism in patients treated Day +100
Secondary Number of Participants Survived One Year Post-transplant The probability of survival, one year post-treatment 1 year
Secondary Number of Participants With Neutrophil Recovery The incidence of neutrophil recovery, that is return of neutrophil counts to = 5 X 10^8/L in treated patients Day 42
Secondary Number of Participants With Platelet Recovery The incidence of platelet recovery (return of platelet counts to > 20,000/µL) in treated patients 1 year
Secondary Number of Participants With Chronic GVHD The incidence of chronic GVHD in treated patients after one year 1 year
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