Multi-institutional Prospective Research of Expanded Multi-antigen Specifically Oriented Lymphocytes for the Treatment of VEry High Risk Hematopoietic Malignancies (RESOLVE)
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|ClinicalTrials.gov Identifier: NCT02203903|
Recruitment Status : Recruiting
First Posted : July 30, 2014
Last Update Posted : July 14, 2020
|Condition or disease||Intervention/treatment||Phase|
|Relapsed/Refractory Hematopoietic Malignancies, Acute Myeloid Leukemia and MDS||Biological: Tumor associated antigen lymphocytes (TAA-T)||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||90 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Multi-institutional Prospective Phase I Research of Expanded Multi-antigen Specifically Oriented Lymphocytes for the Treatment of VEry High Risk Hematopoietic Malignancies|
|Actual Study Start Date :||January 1, 2015|
|Estimated Primary Completion Date :||November 30, 2024|
|Estimated Study Completion Date :||June 28, 2025|
Experimental: Tumor associated antigen lymphocytes (TAA-T)
For Arm A Patients (post-HSCT): TAA-T will be infused any time after neutrophil engraftment post-HSCT or day 30, whichever comes first.
For Arm B Patients (pre-HSCT): TAA-T will be infused any time > 7 days after previous therapy for relapsed disease.
For Arm C Patients (post-HSCT): 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.
Five different dosing levels will be evaluated. Two to four patients will be evaluated on each dosing schedule (see below). This protocol is designed as a phase I dose-escalation study.
Dose Level One: 5 x 106 cells/m2 Dose Level Two: 1 x 107 cells/m2 Dose Level Three: 2 x 107 cells/m2 Dose Level Four: 4 x 107 cells/m2 Dose Level Five: 1 x 108 cells/m2 (ONLY applicable to Arm A patients)
Arm C patients will ONLY be enrolled at: Dose Level Four (4 x 107 cells/m2)
Biological: Tumor associated antigen lymphocytes (TAA-T)
TAA-T may be generated from donors or recipients and will be tested for specificity to 3 tumor antigens commonly found in hematological malignancies (WT1, PRAME, and SURVIVIN,). The goal of this cell infusion will be to initiate an immune response to residual leukemia or lymphoma that includes multiple antigens and may prevent tumor evasion (through decreased expression of a single antigen).
- Safety of investigational product (TAA-T) [ Time Frame: within 45 days of the last dose of TAA-T ]Safety including acute GVHD grades III-IV within 45 days of the last dose of TAA-T or grades 3-5 infusion-related adverse events within 45 days of the last TAA-T dose or grades 4-5 non-hematological attributable adverse events within 45 days of the last 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 NCI Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03. For Arm C, the primary endpoint is to determine if event-free survival (EFS) is improved with TAA-T administration at six months after HSCT for patients with high risk acute myeloid leukemia and MDS.
- Tumor associated antigen lymphocytes (TAA-T) responses [ Time Frame: 2 years ]- To determine the number of patients who respond to tumor associated antigen lymphocytes (TAA-T) for the treatment for relapsed/refractory hematopoietic malignancies as defined by those who achieve CR, PR, MR, or SD following cell infusion and evaluate if this was associated with in vivo persistence of TAA-T.
- The incidence and severity of acute and/or chronic GVHD [ Time Frame: 2 years ]To determine the incidence and severity of acute and/or chronic GVHD in patients treated with TAA-T and compare this to historical controls
- Event free and overall survival [ Time Frame: 1 year ]- Event free and overall survival at 1 year for patients enrolled under Arm A and B. Event-free survival at 6 months and overall survival at 1 year after HSCT for patients enrolled under Arm C.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02203903
|Contact: Fahmida Hoq, MBBS, MSemail@example.com|
|United States, District of Columbia|
|Childrens National Medical Center||Recruiting|
|Washington, District of Columbia, United States, 20010|
|Contact: David Jacobsohn, MD 202-476-6250 DAJacobs@childrensnational.org|
|Principal Investigator: David Jacobsohn, MD|
|United States, Maryland|
|Kenneth R. Cooke, MD||Recruiting|
|Baltimore, Maryland, United States, 21287|
|Contact: Kenneth R. Cooke, MD kcooke5@JHMI.edu|
|Principal Investigator: Kenneth R. Cooke, MD|