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Phase I/II Study of Engineered T Cell Receptor-Modified NK Cells Targeting PRAME in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapse/Refractory Myeloid Malignancies | Clinical Trials | Clareo Health

RECRUITINGPHASE1/PHASE2

Phase I/II Study of Engineered T Cell Receptor-Modified NK Cells Targeting PRAME in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapse/Refractory Myeloid Malignancies

NCT06383572•M.D. Anderson Cancer Center

View on ClinicalTrials.gov

Summary

To find a recommended dose of PRAME-TCR-NK cells that can be given to patients with AML or MDS.

Detailed Description

PRIMARY OBJECTIVE: I. To assess dose-limiting toxicity (DLT) and determine the safety, day 30 response rate, day 180 treatment failure rate (defined as disease progression or death) and optimal cell dose of T cell receptor (TCR) modified cord blood-natural killer (CB-NK) cells (TCR-NK) targeting PRAME in patients with relapsed/refractory myeloid malignances, for each of the following diseases; AML, and MDS/CMML. The day 30 response rate and day 180 treatment failure rate will be estimated, and the estimates will be used to identify an optimal dose of PRAME-TCR-NK cells. SECONDARY OBJECTIVES: I. To assess the preliminary efficacy of PRAME-TCR-NK cells (day+ 30 complete and partial response rates; day 180 progression-free survival rate) in patients with relapsed/refractory AML and MDS. II. To quantify persistence of infused allogeneic donor PRAME-TCR CB-derived NK cells in the recipient as an integrated evaluation. III. To conduct comprehensive immune reconstitution studies. IV. To obtain preliminary data on quality of life and patient experience (Patient Reported Outcomes Measurement Information Systems \[PROMIS\]-29 quality of life questionnaire score). OUTLINE: This is a phase I dose-escalation study of PRAME-TCR-NK followed by a phase II study. Patients receive dexamethasone orally (PO) on days -10, -9, -8, -7, and -6, decitabine intravenously (IV) over 1 hour on days -6, -5, and -4, fludarabine IV over 30 minutes and cyclophosphamide IV over 60 minutes on days -5, -4, and -3 and PRAME-TCR-NK cells IV over 2-20 minutes on day 0. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) and computed tomography (CT) or chest x-ray pre-treatment and bone marrow aspiration and biopsy, and blood sample collection throughout the study. After completion of study treatment, patients are followed up for 24 months then for at least 15 years per protocol PA17-0483. Sponsor: M D Anderson Cancer Center Lead Organization: M D Anderson Cancer Center Principal Investigator: Ramdial, Jeremy Responsible Party: Sponsor Overall Official: Ramdial, Jeremy (Principal Investigator), M D Anderson Cancer Center

Eligibility

Age

18 - 80 years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. 18- 80 years of age. English and non-English speaking patients are eligible.
•2. Patients with one of the following hematological malignances: AML, MDS/CMML. Patients must meet disease specific eligibility criteria (see below)
•3. Patients at least 7 days from last cytotoxic chemotherapy at the time of starting lymphodepleting chemotherapy, except for Hydroxyurea which is allowed for peripheral blood count control in AML patients until the day prior to administration of lymphodepleting chemotherapy. Patients may continue tyrosine kinase inhibitors or other targeted therapies until up to three days prior to administration of lymphodepleting chemotherapy.
•4. Localized radiotherapy to one or more disease sites is allowed prior the infusion provided that there are additional disease sites that are not irradiated to assess response.
•5. Karnofsky Performance Scale \> 50%.
•6. Adequate organ function: as described in 7-10
•7. Renal: Serum creatinine \</= 2.0 mg/dL and estimated Glomerular Filtration Rate (eGFR using the CKD-EPI equation).GFR = 141 x \[min(Scr/k), 1)a x max (Scr/k), 1) -1.209\] x Age-0.993 x 1.018 \[if female\] x \[ 1.157 if Black\] (a is 0.329 for females and 0.411 for males; min indicates minimum of Scr/k or 1, and max indicates maximum of Scr/k or 1)
•8. Hepatic: ALT/AST \</= 2.5 x ULN or \</= 5 x ULN if documented liver metastases, Total bilirubin \</= 1.5 mg/dL, except in subjects with Gilbert's Syndrome in whom total bilirubin must be \</= 3.0 mg/dL. No history of liver cirrhosis. No ascites.
•9. Cardiac: Cardiac ejection fraction \>/= 40%, no clinically significant pericardial effusion as determined by an ECHO/MUGA, and no uncontrolled arrhythmias or symptomatic cardiac disease.
•10. Pulmonary: No clinically significant pleural effusion (per PI discretion), baseline oxygen saturation \> 92% on room air and adequate pulmonary function with FEV1, FVC and DLCO (corrected for Hgb) \>50%.
+9 more criteria

Exclusion Criteria

•1. Relapsed AML is defined as patients who had a first complete remission (CR) before developing recurrent disease.
•2. Refractory AML is defined as patients that have not achieved a CR after 2 cycles of standard induction chemotherapy.
•OR determining the eligibility of the patient. For example, patients who received hypomethylating agents and venetoclax for the treatment of the MDS are not required to receive again hypomethylating agents and venetoclax to treat the secondary AML to be eligible. Similarly, patients who received two lines of therapy for the management of the MDS or MPD are not required to receive an additional two lines of therapy for the management of the AML to be eligible. Patients who relapse after allogeneic stem cell transplantation are eligible irrespective of the number and type of therapy received prior transplant.
•Myelodysplastic syndromes (MDS)/Chronic myelomonocytic leukemia (CMML):one of the following:
•1. Patients with high risk or intermediate risk MDS/CMML who have received at least two lines of therapy and have positive MRD at a level of \>0.1% measured by multiparameter flow cytometry or are not in morphological remission.
•OR
•2. Patients with relapse high risk or intermediate risk MDS/CMML after at least 2 lines of therapy. Relapse is defined as positive MRD at a level of \>0.1% measured by multiparameter flow cytometry or loss of morphological remission.
•OR
•3. CMML patients with refractory disease defined as failure to achieve complete remission after 4 therapy cycles of hypomethylating agent therapy or relapse or progression after any number of cycles of therapy.
•4. Patients with MDS/CMML who relapse after allogeneic stem cell transplantation are eligible irrespective of the number and type of therapy received prior to transplant.
+32 more criteria

Locations (1)

MD Anderson Cancer Center

Houston, Texas, United States

Key Dates

Start Date

June 26, 2024

Primary Completion Date

April 1, 2027

Completion Date

April 1, 2029

Last Updated

December 23, 2025

Enrollment

ESTIMATED participants

Conditions

Lymphodepleting ChemotherapyMyeloid Malignancies

Interventions

Cyclophosphamide

DRUG

Fludarabine phosphate

DRUG

Decitabine

DRUG

Dexamethasone

DRUG

Contacts

Jeremy Ramdial, MD

CONTACT

(713) 745-0146 jlramdial@mdanderson.org

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: December 23, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Phase I/II Study of Engineered T Cell Receptor-Modified NK Cells Targeting PRAME in Conjunction With Lymphodepleting Chemotherapy for the Management of Relapse/Refractory Myeloid Malignancies

Inclusion Criteria

Exclusion Criteria

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