Multi-institutional Prospective Research of Expanded Multi-antigen Specifically Oriented Lymphocytes for the Treatment of VEry High Risk Hematopoietic Malignancies
- Conditions
- Relapsed/Refractory Hematopoietic Malignancies, Acute Myeloid Leukemia and MDS
- Interventions
- Biological: Tumor associated antigen lymphocytes (TAA-T)
- Registration Number
- NCT02203903
- Lead Sponsor
- Catherine Bollard
- Brief Summary
This Phase I dose-escalation trial is designed to evaluate the safety of administering rapidly -generated tumor multi-antigen associated -specific cytotoxic T lymphocytes, to HSCT recipients with high risk AML and MDS.
- Detailed Description
Patients with evidence of high-risk or relapsed or persistent hematopoietic malignancies (for example but not limited to: acute myeloid leukemia and myelodysplastic syndrome (MDS)) will be eligible for this study.
Patients with high risk for relapse will be eligible to receive planned infusion of allogeneic TAA-T after HSCT (with high risk AML and MDS who have undergone allo-HSCT and are in a hematologic remission).
We will utilize our established protocol for the manufacture of tumor multi-antigen associated specific cytotoxic T lymphocytes. Peripheral blood mononuclear cells will be exposed to antigen presenting cells pulsed with peptides to tumor antigens (PRAME, WT1, Survivin) in a cytokine milieu favorable to T cell expansion/activation, inducing selective expansion of T cells targeted to kill tumor cells. Patients would be monitored for the development of toxicity. In patients with disease at the time of TAA-T infusion, efficacy would be evaluated as a secondary endpoint using standard criteria. Exploratory investigational analyses would include monitoring of cytokine and cellular milieu pre- and post- TAA-T infusion and in vitro characterization of the host tumor, donor lymphocyte product, and TAA-T product.
TAA-T will be infused any time after neutrophil engraftment post-HSCT or day 30, whichever comes first at dose level 4 . Infusions will be within first 5 months post-HSCT.
Patients will receive a TAA-T cell dose of 4 x 107 cells/m2.
Each patient will receive at least one infusion according to the enrolled dose level, where the expected volume of infusion is 1 to 10 cc.
If patients with active disease (defined as MRD+ at the time of TAA-T infusion) do not have ≥ grade 3 toxicity that is possibly, probably, or definitely attributed to TAA-T infusion and fail to rapidly progress with disease requiring urgent therapy, patients may receive a subsequent TAA-T cell dose (infusion #2). A subsequent dose (infusion #2) will also be available for those patients who have stable disease or a mixed, partial, or complete response (including continued complete response) by the International Working Group (IWG) criteria (see section 4.2.1) at the evaluation after the first TAA-T infusion.
Patients who have received at least 2 infusions of TAA-T are eligible to receive up to 6 additional doses (infusion #3 to #8) of TAA-T at monthly intervals each of which will consist of the same cell number as their enrolled dose level. Patients will not be able to receive additional doses until the initial safety profile is completed at 28 days following the second infusion. Notably, these doses will be identical to the treated dose for this patient (i.e. no subsequent dose escalation). Patients would then receive additional doses starting greater than 28 days from second infusion and be treated at the same dose level as he/she has previously received.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 50
-
Donors for allogeneic (i.e. HLA matched or mismatched related or unrelated) stem cell transplants who have undergone eligibility evaluation as per FDA regulations outlined in 21 CFR 1271 subpart C. If a donor has been chosen for the transplant based on urgent medical need, that same donor will also be used for TAA-T generation provided that there are no new reasons for ineligibility since the transplant donor evaluation.
-
Aged 6 months to 80 years.
-
Donor or guardian of pediatric capable of providing informed consent.
-
Donor must have completed infectious Disease (ID) testing up to 7 days before or after the collection of blood from the donor (related or unrelated) for TAA-T manufacturing. The following tests will be performed:
- HBsAg
- HB Core antibody
- HIV1/2 NAT
- Syphilis (T. Pallidum IgG)
- HTLV I/II
- CMV total
- HBV/HCV NAT
- West Nile Virus NAT.
- Cruz (Chagas) antibody
- Hepatitis C
-
Female donors of childbearing age must have a negative pregnancy test within 7 days of blood collection for TAA-T manufacturing.
Donor
- Donation of cells would pose a physical or psychological risk to the donor.
- Female donors of childbearing age who are known to be pregnant.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Tumor associated antigen lymphocytes (TAA-T) Tumor associated antigen lymphocytes (TAA-T) TAA-T will be infused any time after neutrophil engraftment post-HSCT or day 30, whichever comes first. All infusions will be within 5 months post-HSCT. Patients will receive a TAA-T cell dose of 4 x 107 cells/m2.
- Primary Outcome Measures
Name Time Method Safety of investigational product (TAA-T) 45 days Acute GVHD grades III-IV within 45 days of the last dose of TAA-T
Event-free survival Twelve months post-HSCT To determine if event-free survival (EFS) at twelve months post-HSCT is improved with TAA-T administration for AML and MDS (Arm C).
Safety of TAA-T cells 45 days Grades 3-5 infusion-related adverse events within 45 days of the last dose of TAA-T
Safety of TAA-Ts 45 days Grades 4-5 non-hematological attributable adverse events within 45 days of TAA-T dose and that are not due to the pre-existing infection or the original malignancy or pre-existing co-morbidities as defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0
- Secondary Outcome Measures
Name Time Method Tumor associated antigen lymphocytes (TAA-T) responses 2 years To determine the number of patients who respond to tumor multi-antigen associated specific cytotoxic lymphocytes (TAA-T) for treatment for high risk or relapsed or refractory hematopoietic malignancies as defined by those who maintain or achieve CR, PR, MR or SD following TAA-T infusion and evaluate if this was associated with in vivo persistence of TAA-T
Trial Locations
- Locations (2)
Tania Jain, MD
🇺🇸Baltimore, Maryland, United States
Childrens National Medical Center
🇺🇸Washington, District of Columbia, United States
Tania Jain, MD🇺🇸Baltimore, Maryland, United StatesTania Jain, MDPrincipal Investigator