Clinical Study of Anti-FLT3 CAR-T Cells for the Treatment of Relapsed/Refractory AML

NCT06786533 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: HEM-001-AML-1101IND 029573
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 1 dose escalation study to determine the safety of anti-FLT3 CAR-T in subjects with R/R AML. The primary objective is to assess safety. Up to 18 evaluable adult and 18 evaluable pediatric subjects will be enrolled. Evaluable subjects are defined as those who have received an infusion of HG-CT-1. Primary clinical objectives: i. Determine the safety of HG-CT-1 based on the proportion of subjects infused with HG-CT-1 who experience a dose limiting toxicity (DLT). Secondary clinical objectives: i. Estimate the efficacy of HG-CT-1 according to standard clinical response criteria for AML. ii. Estimate overall survival of evaluable subjects. iii. Estimate progression-free survival of evaluable subjects. iv. Estimate duration of response in evaluable subjects who achieve a response. Secondary scientific objectives: i. Describe the persistence and trafficking of HG-CT-1. ii. Describe HG-CT-1 bioactivity and its predictors.

Conditions

Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)

Outcome Measures

Primary Outcomes (1)

• Determine the safety of HG-CT-1 cells based on the proportion of subjects infused with HG-CT-1 who experience a DLT.

  Occurrence of dose-limiting toxicities related to HG-CT-1. First-in-human study with unknown safety of infusion of HG-CT-1.

  From the time of HG-CT-1 infusion until Day 28

Secondary Outcomes (4)

• Estimate the efficacy of HG-CT-1 cells as defined by clinical response according to established criteria for AML.

  Day 14, Day 28, Month 3, Month 6 and Month 12

• Estimate the Overall Survival (OS).

  At 6 months and 1 year

• Estimate the progression-free survival (PFS).

  At 6 months and 1 year

• Estimate the Duration of response (DOR).

  At 6 months and 1 year

Study Arms (4)

Dose level 1: 7x10^7 Transduced CAR+ HG-CT-1

EXPERIMENTAL

Drug: Anti-FLT3 CAR-T cells

Dose level 2: 1.4x10^8 Transduced CAR+ HG-CT-1

EXPERIMENTAL

Dose level 3: 3.5x10^8 Transduced CAR+ HG-CT-1

EXPERIMENTAL

Drug: Anti-FLT3 CAR-T cells

Dose level -1: 3.5 x 10^7 Transduced CAR+ HG-CT-1

EXPERIMENTAL

Drug: Anti-FLT3 CAR-T cells

Interventions

Anti-FLT3 CAR-T cells DRUG

Anti-FLT3 CAR-T cells is administered by intravenous infusion following standard lymphodepleting chemotherapy consisting of fludarabine and cyclophosphamide.

Also known as: HG-CT-1

Dose level -1: 3.5 x 10^7 Transduced CAR+ HG-CT-1; Dose level 1: 7x10^7 Transduced CAR+ HG-CT-1; Dose level 3: 3.5x10^8 Transduced CAR+ HG-CT-1

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older at enrollment. Patients ≥12 and \<18 12 to 17 years of age weighing ≥ 35 kg at enrollment may be included once safety evaluation at the corresponding adult dose escalation protocol have been completed.
• Subjects with AML unlikely to be cured with currently available therapies. Specifically, the following groups are eligible:
• Refractory AML: i.e., newly diagnosed AML that after two cycles of intensive chemotherapy has not achieved a complete remission or morphologic leukemia free state by ELN criteria.1 Intensive chemotherapy must have included either the combination of cytarabine and an anthracycline (7+3 or similar) or combination of venetoclax with a hypomethylating agent.
• Patients with FLT3 ITD must also have failed treatment with a FLT3 inhibitor and patients with IDH1 or IDH2 mutations must have failed treatment containing ivosidenib or enasidenib respectively (i.e., progression on treatment, or failure to achieve CR after six months of treatment,) OR:
• AML relapsed following allogeneic stem cell transplantation (including MDS evolved to AML post-allogeneic stem cell transplantation). Note: morphologic relapse is not required; persistent/recurrent disease-associated molecular, phenotypic, or cytogenetic abnormalities (measurable residual disease, MRD) at any time after allogeneic HSCT is eligible. OR:
• AML that has relapsed within 12 months after initial induction and consolidation therapy OR:
• AML that has relapsed more than 12 months after initial induction but that has failed to achieve CR or morphologic leukemia free state after one reinduction OR:
• AML after second or subsequent relapse.
• FLT3 expression must be detectable in AML blast by flow cytometric analysis.
• Subjects must have a suitable stem cell transplant donor. Donor may be matched or mismatched and must be found to be suitable according to the institution's standard criteria. That donor shall be "cleared" for donation by institutional standards prior to administration of HG-CT-1. Adult donors can be either related or unrelated, HLA-matched or partially matched. Matched or partially matched umbilical cord blood donors are also eligible.
• Subjects with relapsed disease after prior allogeneic transplant must be off systemic immunosuppression for at least 1 month at the time of enrollment without GvHD that requires systemic immunosuppression.
• Satisfactory organ functions:
• Creatinine ≤ 1.6 mg/dl and Creatinine clearance (CrCl) as calculated by the Cockcroft-Gault formula ≥ 60 mL/min.
• ALT/AST must be ≤ 3 x upper limit of normal unless related to disease.
• Direct bilirubin \< 2.0mg/dl unless subject has Gilbert's syndrome (in which case it should be ≤3.0 mg/dL).

You may not qualify if:

• Pregnant or lactating (nursing) women.
• Active second malignancy will not be eligible with the following exceptions:
• Carcinoma in situ of the cervix (which may be considered for enrollment),
• Indolent, non-metastatic prostate cancer
• Non melanoma skin cancer
• Other indolent and controlled malignancies not requiring urgent treatment.
• Subjects with a history of a prior allogeneic stem cell transplantation are excluded if:
• Subjects are less than 100 days post-transplant OR
• Subjects have evidence of ongoing active GvHD and are taking immunosuppressive agents (\>0.5mg/kg/methylprednisolone equivalents or other immunosuppression for GvHD treatment) OR
• Subjects have received DLI within 30 days prior to enrollment.
• Concurrent use of immunosuppressant medications such as calcineurin inhibitors, methotrexate, or alemtuzumab.
• Uncontrolled, symptomatic, intercurrent illness including but not limited to infection, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the site Pl would pose an unacceptable risk to the subject.
• Active or uncontrolled viral, bacterial, or fungal infection. May be receiving ongoing therapy for controlled infection.
• Known history of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
• Hyperleukocytosis (\>50,000 blasts/µL) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy.

Sponsors & Collaborators

• Hemogenyx Pharmaceuticals LLC: lead
• M.D. Anderson Cancer Center: collaborator

Study Sites (1)

MD Anderson

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Recurrence; Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Dose and route of administration HG-CT-1 cells will be administered by intravenous infusion following standard lymphodepleting chemotherapy consisting of fludarabine and cyclophosphamide. Statistical Design The trial will use a modified toxicity probability interval (mTPI-2) design while matching the cohort size with the traditional 3 + 3 design. Dose Levels Dose level 1: 7x10\^7 Transduced CAR+ HG-CT-1 Dose level 2: 1.4x10\^8 Transduced CAR+ HG-CT-1 Dose level 3: 3.5x10\^8 Transduced CAR+ HG-CT-1 If Dose level 1 is found not to be safe, dose will be de-escalated to 3.5 x 10\^7 Transduced CAR+ HG-CT-1. (Dose level -1) Pediatric Dosing: Enrollment on any pediatric (≥12 and \<18 years of age) cohort shall begin after the corresponding adult cohort has been safely completed.

Study Record Dates

• First Submitted: January 10, 2025
• First Posted: January 22, 2025
• Study Start: January 23, 2025
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: August 14, 2025

Record last verified: 2025-08

Locations

US (1)