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 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2024-0196NCI-2024-03505
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Lymphodepleting Chemotherapy; Myeloid Malignancies

Outcome Measures

Primary Outcomes (1)

• Safety and adverse events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year.

Study Arms (1)

Phase 1 (Dose Escalation and Dose Expansion)

EXPERIMENTAL

Participants will be assigned to a dose level of the NK cell treatment based on when you join this study. Up to 4 dose levels of the treatment will be tested. The first group of participants will receive the lowest dose level. Each new group will receive a higher dose than the group before it, if no intolerable side effects were seen. This will continue until the highest tolerable dose of the NK cell treatment is found.

Drug: Cyclophosphamide; Drug: Fludarabine phosphate; Drug: Decitabine; Drug: Dexamethasone

Interventions

Cyclophosphamide DRUG

Given by IV

Also known as: Cytoxan®, Neosar®

Phase 1 (Dose Escalation and Dose Expansion)

Fludarabine phosphate DRUG

Given by IV

Also known as: Fludarabine, Fludara®

Phase 1 (Dose Escalation and Dose Expansion)

Decitabine DRUG

Given by IV

Also known as: Dacogen

Phase 1 (Dose Escalation and Dose Expansion)

Dexamethasone DRUG

Given by mouth

Also known as: Decadron

Phase 1 (Dose Escalation and Dose Expansion)

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age. English and non-English speaking patients are eligible.
• Patients with one of the following hematological malignances: AML, MDS/CMML. Patients must meet disease specific eligibility criteria (see below)
• 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.
• 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.
• Karnofsky Performance Scale \> 50%.
• Adequate organ function: as described in 7-10
• 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)
• 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.
• Cardiac: Cardiac ejection fraction \>/= 40%, no clinically significant pericardial effusion as determined by an ECHO/MUGA, and no uncontrolled arrhythmias or symptomatic cardiac disease.
• 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%.
• Able to provide written informed consent.
• All participants who are able to have children must practice effective birth control while on study and up to 3 months post completion of study therapy. Acceptable forms of birth control for female patients include: hormonal birth control, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence, for the length of the study. If the participant is a female and becomes pregnant or suspects pregnancy, she must immediately notify her doctor. If the participant becomes pregnant during this study, she will be taken off this study.
• a. Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physicaian immediately.
• Men treated or enrolled on this protocol must also agree to use adequate contraception, such as subject post vasectomy, partner with implantable or oninjectable contraceptives, and condoms plus spermicide, prior to the study, for the duration of study participation, and 4 months after completion of study agent administration. Men who are able to have children must use effective birth control while on the study. If the male participant fathers a child or suspects that he has fathered a child while on the study, he must immediately notify his doctor.
• Signed consent to long-term follow-up protocol PA17-0483 to fulfill the institutional responsibilities to various regulatory agencies.

You may not qualify if:

• Positive beta HCG in female of child-bearing potential defined as not postmenopausal for 24 months or no previous surgical sterilization or lactating females.
• Presence of clinically significant Grade 3 or greater toxicity from the previous treatment, as determined by PI.
• Presence of uncontrolled fungal, bacterial, viral, or other infection not responding to appropriate therapy.
• Known active hepatitis B or C.
• Known HIV with detectable viral load
• Presence of active neurological disorder(s).
• Active autoimmune disease within 12 months of enrollment
• Active cerebral or meningeal involvement by the malignancy
• Active (defined as requiring therapy) acute or chronic GVHD
• Any other malignancy known to be active, except for treated cervical intra-epithelial neoplasia and non-melanoma skin cancer.
• Presence of any other serious medical condition that may endanger the patient at investigator discretion.
• Major surgery \<4 weeks prior to first dose of the preparatory chemotherapy
• Allogeneic SCT or DLI \<12 weeks prior to first dose of preparatory chemotherapy
• Concomitant use of other investigational agents.
• Concomitant use of other anti-cancer agents.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Interventions

Cyclophosphamide; fludarabine phosphate; fludarabine; Decitabine; Dexamethasone; Calcium Dobesilate

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Azacitidine; Aza Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Jeremy Ramdial, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jeremy Ramdial, MD

CONTACT

(713) 745-0146; jlramdial@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2024
• First Posted: April 25, 2024
• Study Start: June 26, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2029
• Last Updated: December 23, 2025

Record last verified: 2025-12

Locations

US (1)