Relapsed/Refractory Hematopoietic Malignancies, Acute Myeloid Leukemia and MDSPhase 1RESOLVENCT02203903
Multi-institutional Prospective Research of Expanded Multi-antigen Specifically Oriented Lymphocytes for the Treatment of VEry High Risk Hematopoietic Malignancies
A Phase 1 study testing Tumor associated antigen lymphocytes (TAA-T) in people with Relapsed/Refractory Hematopoietic Malignancies, Acute Myeloid Leukemia and MDS, run by Catherine Bollard at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 months to 80 years
- Conditions the study is for
- Relapsed/Refractory Hematopoietic Malignancies, Acute Myeloid Leukemia and MDS
- What is being tested?
- Tumor associated antigen lymphocytes (TAA-T)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 2 sitesUnited States
- Study dates
- 2 Apr 2015to 28 Jun 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Recipient Inclusion Criteria to Enter Protocol:
- Aged 6 months to 80 years.
- Anticipated myeloablative or non-myeloablative allogeneic hematopoietic stem cell transplant.
- Patients with high risk AML and MDS who have received or will receive 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
Recipient Exclusion Criteria to Enter Protocol:
- Patients with uncontrolled infections.
- Current evidence of GVHD > grade 2 or bronchiolitis obliterans syndrome, sclerotic GVHD, or serositis.
- Pregnancy (female of childbearing potential).
Recipient Inclusion Criteria for TAA-T Administration:
- 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 in the context of no escalation of treatment within the preceding 2 weeks
- 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 TAA-T Administration:
- 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.
- Uncontrolled infections.
- Active Bronchiolitis obliterans syndrome, sclerotic GVHD, or serositis.
- Active acute GVHD or chronic GVHD requiring escalation of treatment within preceding 2 weeks of any grade is exclusion for Arm C patients.
- Pregnancy or lactating (female of childbearing potential).
- Patients who have or will be receiving 2nd allogeneic HSCT
Donor Inclusion Criteria:
- 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 Exclusion Criteria:
- Donation of cells would pose a physical or psychological risk to the donor.
- Female donors of childbearing age who are known to be pregnant.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Tania Jain, MD
Baltimore, Maryland, 21287
Tania Jain, MD, tjain2@jhmi.edu
Tania Jain, MD
- Recruiting
Childrens National Medical Center
Washington D.C., District of Columbia, 20010
Keri Toner, MD, 202-476-7538, KToner@childrensnational.org
Keri Toner, MD
About this study
Official title: Multi-institutional Prospective Phase I Research of Expanded Multi-antigen Specifically Oriented Lymphocytes for the Treatment of VEry High Risk Hematopoietic Malignancies
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.
Read the 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.
- Being tested
- Tumor associated antigen lymphocytes (TAA-T)
- Medical subject headings
- Recurrence, Hematologic Neoplasms, Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Tumor associated antigen lymphocytes (TAA-T)Biological
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).
| Study group | Role | What they receive |
|---|---|---|
| Tumor associated antigen lymphocytes (TAA-T) | Experimental | 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. Receives: Biological: Tumor associated antigen lymphocytes (TAA-T) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of investigational product (TAA-T)
Acute GVHD grades III-IV within 45 days of the last dose of TAA-T
Measured: 45 days
Safety of TAA-T cells
Grades 3-5 infusion-related adverse events within 45 days of the last dose of TAA-T
Measured: 45 days
Safety of TAA-Ts
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
Measured: 45 days
Event-free survival
To determine if event-free survival (EFS) at twelve months post-HSCT is improved with TAA-T administration for AML and MDS (Arm C).
Measured: Twelve months post-HSCT
Secondary outcomes (1)
Tumor associated antigen lymphocytes (TAA-T) responses
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
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jul 2014 (estimated)
- Study start2 Apr 2015
- Primary completion30 Nov 2026 (estimated)
- Study completion28 Jun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Relapsed/Refractory Hematopoietic Malignancies, Acute Myeloid Leukemia and MDSStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Catherine Bollard
- Sponsor type
- University, hospital or other
- Collaborators
- Children's National Research Institute, Johns Hopkins University
- Responsible party
- Sponsor-investigator, Catherine Bollard, Children's National Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02203903
- Sponsor's protocol ID
- Pro00005533
- Acronym
- RESOLVE
- Status last verified
- Aug 2026
- First submitted
- 25 Jul 2014
- Last updated
- 14 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Kinoshita H, Cooke KR, Grant M, Stanojevic M, Cruz CR, Keller M, Fortiz MF, Hoq F, Lang H, Barrett AJ, Liang H, Tanna J, Zhang N, Shibli A, Datar A, Fulton K, Kukadiya D, Zhang A, Williams KM, Dave H, Dome JS, Jacobsohn D, Hanley PJ, Jones RJ, Bollard CM. Outcome of donor-derived TAA-T cell therapy in patients with high-risk or relapsed acute leukemia post allogeneic BMT. Blood Adv. 2022 Apr 26;6(8):2520-2534. doi: 10.1182/bloodadvances.2021006831.
PubMed 35244681
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-institutional Prospective Phase I Research of Expanded Multi-antigen Specifically Oriented Lymphocytes for the Treatment of VEry High Risk Hematopoietic Malignancies
- ClinicalTrials.gov ID
- NCT02203903
- Acronym / sponsor ID
- RESOLVE / Pro00005533
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Catherine BollardUniversity, hospital or other
- Collaborators
- Children's National Research Institute, Johns Hopkins University
- Study start
- 2 Apr 2015 (actual)
- Primary completion
- 30 Nov 2026 (estimated)
- Study completion
- 28 Jun 2027 (estimated)
- First posted
- 30 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tumor associated antigen lymphocytes (TAA-T) | Experimental | Biological: 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. |
Who may qualify
- Ages
- 6 months to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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). | Biological | Tumor associated antigen lymphocytes (TAA-T) |
Primary outcome
Safety of investigational product (TAA-T)
Time frame: 45 days
Acute GVHD grades III-IV within 45 days of the last dose of TAA-T
Safety of TAA-T cells
Time frame: 45 days
Grades 3-5 infusion-related adverse events within 45 days of the last dose of TAA-T
Safety of TAA-Ts
Time frame: 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
Event-free survival
Time frame: 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).
1 secondary outcome
Tumor associated antigen lymphocytes (TAA-T) responses
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2026.
- Derived from this study: PubMed 35244681Kinoshita H, Cooke KR, Grant M, Stanojevic M, Cruz CR, Keller M, Fortiz MF, Hoq F, Lang H, Barrett AJ, Liang H, Tanna J, Zhang N, Shibli A, Datar A, Fulton K, Kukadiya D, Zhang A, Williams KM, Dave H, Dome JS, Jacobsohn D, Hanley PJ, Jones RJ, Bollard CM. Outcome of donor-derived TAA-T cell therapy in patients with high-risk or relapsed acute leukemia post allogeneic BMT. Blood Adv. 2022 Apr 26;6(8):2520-2534. doi: 10.1182/bloodadvances.2021006831.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Tumor associated antigen lymphocytes (TAA-T) in people with Relapsed/Refractory Hematopoietic Malignancies, Acute Myeloid Leukemia and MDS, run by Catherine Bollard at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Fahmida Hoq, MBBS, MS (202-476-3634, fhoq@childrensnational.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of investigational product (TAA-T) (time frame: 45 days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02203903, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2026.