Clinical trial NCT02991898: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: 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
Keywords: CML
MDS
CLL
ALL
AML
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2016-12-14
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of Participants Survived
timeFrame: 2 years
Secondary outcomes:
measure: Number of Participants With Grade II-IV aGVHD
timeFrame: Assessed weekly until day 100, then day 180, 360
measure: Number of Participants Experiencing Treatment Related Mortality (TRM)
timeFrame: 6 months
measure: Number of Participants Who Experienced Relapse
timeFrame: 1 year
measure: Number of Participants With Incidence of Bacterial, Viral and Fungal Infections
timeFrame: 1 year
measure: Number of Participant With Detectable Treg Cells at d14
timeFrame: 14 days
measure: Number of Participants With Immune Reconstitution
timeFrame: Assessed at Day 4, weekly for 8 weeks
measure: Number of Participants Experiencing Treg Cell Infusion Toxicity
timeFrame: 48 hours post infusion
measure: Length of Treg Survival
timeFrame: 24 hours post infusion
measure: Percentage of Donor Cell Chimerism
timeFrame: Day +100
measure: Number of Participants Survived One Year Post-transplant
timeFrame: 1 year
measure: Number of Participants With Neutrophil Recovery
timeFrame: Day 42
measure: Number of Participants With Platelet Recovery
timeFrame: 1 year
measure: Number of Participants With Chronic GVHD
timeFrame: 1 year
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center at University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Claudio Brunstein, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: