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

NCT02991898 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2016LS107MT2016-17
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants Survived

  Count of patients who survived 2 years post intervention

  2 years

Secondary Outcomes (13)

• Number of Participants With Grade II-IV aGVHD

  Assessed weekly until day 100, then day 180, 360

• Number of Participants Experiencing Treatment Related Mortality (TRM)

  6 months

• Number of Participants Who Experienced Relapse

  1 year

• Number of Participants With Incidence of Bacterial, Viral and Fungal Infections

  1 year

• Number of Participant With Detectable Treg Cells at d14

  14 days

Study Arms (1)

Treg Infusion

EXPERIMENTAL

The Treg cell infusion is given no sooner than 1 hour, but within 24 hours after the 2nd cord blood infusion

Biological: Infusion of Treg

Interventions

Infusion of Treg BIOLOGICAL

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.

Also known as: T regulatory cells

Treg Infusion

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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)
• CML in blast crisis
• Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressing on salvage therapy.
• Active central nervous system malignancy

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Burkitt Lymphoma; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myelodysplastic Syndromes; Dendritic Cell Sarcoma, Interdigitating; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Leukemia, Prolymphocytic; Hodgkin Disease; Multiple Myeloma; Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Leukemia, Myeloid; Myeloproliferative Disorders; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Histiocytic Disorders, Malignant; Histiocytosis; Leukemia, B-Cell; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Results Point of Contact

• Title: Claudio Brunstein
• Organization: Masonic Cancer Center, University of Minnesota

bruns072@umn.edu

612-625-3918

Study Officials

• Claudio Brunstein, MD, PhD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2016
• First Posted: December 14, 2016
• Study Start: February 16, 2017
• Primary Completion: June 20, 2019
• Study Completion: June 20, 2019
• Last Updated: September 29, 2020
• Results First Posted: July 24, 2020

Record last verified: 2020-09

Locations

US (1)