Brief Title
Adoptive TReg Cell for Suppression of aGVHD After UCB HSCT for Heme Malignancies
Official Title
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Number of Participants Survived
Secondary Outcome
Number of Participants With Grade II-IV aGVHD
Condition
Acute Lymphoblastic Leukemia
Intervention
Infusion of Treg
Study Arms / Comparison Groups
Treg Infusion
Description: The Treg cell infusion is given no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
3
Start Date
February 16, 2017
Completion Date
June 20, 2019
Primary Completion Date
June 20, 2019
Eligibility Criteria
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
Gender
All
Ages
18 Years - 75 Years
Accepts Healthy Volunteers
No
Contacts
Claudio Brunstein, MD, PhD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT02991898
Organization ID
2016LS107
Secondary IDs
MT2016-17
Responsible Party
Sponsor
Study Sponsor
Masonic Cancer Center, University of Minnesota
Study Sponsor
Claudio Brunstein, MD, PhD, Principal Investigator, Masonic Cancer Center, University of Minnesota
Verification Date
September 2020