Multi-institutional Prospective Research of Expanded Multi-antigen Specifically Oriented Lymphocytes for the Treatment of VEry High Risk Hematopoietic Malignancies (RESOLVE)
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT02203903 |
Recruitment Status :
Recruiting
First Posted : July 30, 2014
Last Update Posted : July 14, 2020
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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 |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
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 |

Arm | Intervention/treatment |
---|---|
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.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 6 Months to 80 Years (Child, Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Recipient procurement Inclusion criteria:
- Aged 6 months to 80 years
- Received prior or anticipated myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant
-
Patients (Arm A) who have undergone allo-HSCT with high risk or relapse or residual/recurrent disease (see below) OR patients (Arm B) with high risk or relapsed/refractory disease (> 2 regimens with greater than M1 marrow or persistent HD) with anticipated allo-HSCT:
- Acute lymphoblastic leukemia (ALL), Acute myeloid leukemia (AML), Ambiguous lineage leukemia or lymphoma, Chronic Myelogenous leukemia (CML), CMML, MDS:
- Evidence of active leukemia or lymphoma disease by flow cytometry, morphology, or cytogenetic evaluation within the marrow or extramedullary sites.
- Hodgkin's Lymphoma that has failed or are intolerant of Brentuximab, Non-Hodgkin Lymphoma (NHL) including Grey Zone Lymphoma, Anaplastic large cell lymphoma (ALCL), and mantle cell lymphoma:
- Evidence of lymphoma by morphology, Positron Emission Tomography (PET)/ Computed tomography (CT) uptake in a site of previous disease in the absence of other etiologies.
- ARM C only includes patients with high risk AML and MDS who have received an allo-HSCT and have not had hematologic relapse of disease.
- Karnofsky/Lansky score of ≥ 50
- Agree to use contraceptive measures during study protocol participation (when age appropriate)
- Patient or parent/guardian capable of providing informed consent.
- T cell chimerism > 94% if collected from recipient of allo-HSCT (performed within the last 6 months)
- If the product is procured from the recipient in the autologous (Arm B) setting, the absolute lymphocyte count should be greater than or equal to 600 for procurement. Please note: If a patient has already undergone an allogeneic HSCT, it is NOT allowed to generate TAA-T from patient blood collected post-HSCT under Arm A or C
Recipient Procurement Exclusion Criteria:
- Patients with uncontrolled infections
- Current evidence of GVHD > grade 2 or bronchiolitis obliterans syndrome, sclerotic GVHD, or serositis Pregnancy or lactating (female of childbearing potential) Recipient Inclusion criteria for initial TAA-T administration and for subsequent infusions
-
Patients (Arm A) who have undergone allo-HSCT with high risk or relapse or residual/recurrent disease (see below) OR patients (Arm B) with high risk or relapsed/refractory disease (> 2 regimens with greater than M1 marrow or persistent HD) with anticipated allo-HSCT:
o Acute lymphoblastic leukemia (ALL), Acute myeloid leukemia (AML), Ambiguous lineage leukemia or lymphoma, Chronic Myelogenous leukemia (CML), CMML, MDS: Evidence of active leukemia or lymphoma disease by flow cytometry, morphology, or cytogenetic evaluation within the marrow or extramedullary sites.
o Hodgkin's Lymphoma that has failed or are intolerant of Brentuximab, NHL including Grey Zone Lymphoma, ALCL, and mantle cell lymphoma: Evidence of lymphoma by morphology, PET/CT uptake in a site of previous disease in the absence of other etiologies.
o ARM C only includes patients with high risk AML and MDS who have received an allo-HSCT and have not had hematologic relapse of disease.
- Steroids less than 0.5 mg/kg/day prednisone or equivalent.
- Karnofsky/Lansky score of ≥ 50.
- Bilirubin < 2.5 mg/dL, AST/ALT <5x upper limit of normal, Serum creatinine < 1.0 or 2x the upper limit of normal (whichever is higher).
- Pulse oximetry of > 90% on room air.
- Absolute neutrophil count > 250/ µL (may be supported with Granulocyte colony-stimulating factor (GCSF)).
- Agree to use contraceptive measures during study protocol participation (when age appropriate).
- Patient or parent/guardian capable of providing informed consent.
- LVEF > 50% or LVSF > 27% (performed within the last 6 months) if history of TBI >500 cGy for arm A and B.
- Total chimerism > 50%; or if cancer cells preclude this, donor T cell chimerism > 50% (performed within the last 6 months).
Recipient Exclusion criteria for initial and subsequent TAA-T infusions
- Patients who received ATG, Campath, or other T cell immunosuppressive monoclonal antibodies within 28 days prior to TAA-T infusion.
- No investigational therapies (under IND, not extensively studied in the current clinical context) within 28 days prior to TAA-T infusion.
For allogeneic HSCT recipients PD-1 inhibitors or other T cell activating agents will be excluded. For Arm B, if the patient has tolerated these agents without autoimmunity, these may be continued with the TAA-T infusion.
- Uncontrolled infections
- Active Bronchiolitis obliterans syndrome, sclerotic GVHD, or serositis
- Current evidence of GVHD > grade 2 for Arm A and B; Active GVHD of any grade is exclusion for arm C patients.
- Pregnancy or lactating (female of childbearing potential)

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, MS | 202-476-3634 | fhoq@cnmc.org |
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 |
Responsible Party: | Catherine Bollard, Director- Center for Cancer and Immunology Research, Children's National Research Institute |
ClinicalTrials.gov Identifier: | NCT02203903 |
Other Study ID Numbers: |
Pro00005533 |
First Posted: | July 30, 2014 Key Record Dates |
Last Update Posted: | July 14, 2020 |
Last Verified: | July 2020 |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Neoplasms Hematologic Neoplasms Neoplasms by Site Hematologic Diseases |