CD33KO-HSPC Infusion Followed by CART-33 Infusion(s) for Refractory/Relapsed AML

NCT05945849 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: IRB # 854325, UPCC # 26423
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to provide a new type of treatment for AML. This treatment combines a new type of stem cell transplant along with treatment using chimeric antigen receptor (CAR) T cells that have been engineered to recognize and attack your AML cells. The first treatment is a modified stem cell transplant, using blood-forming stem cells donated from a healthy donor. From the same donor, we will also make CAR T-cells, which are leukemia fighting cells, which will be given to the patient via an infusion into the vein after the transplanted stem cells have started to grow healthy blood cells. The modification of the stem cell transplant means that the healthy bone marrow cells will be "invisible" to the CAR T-cells that are trying to kill the leukemia cells.

Conditions

Leukemia, Myeloid, Acute

Outcome Measures

Primary Outcomes (3)

• Manufacturing feasibility

  Proportion of subjects whose Product 1 (CD33KO-HSPC) meets release criteria.

  1 month

• Occurrence of dose-limiting toxicities related to CD33KO-HSPC

  Safety of alloHSCT: occurrence of dose-limiting toxicities related to CD33KO-HSPC

  3 months

• Occurrence of dose-limiting toxicities related to CART-33

  Safety of CART-33: occurrence of dose-limiting toxicities related to CART-33

  6 months

Secondary Outcomes (5)

• Efficacy of CD33KO-HSPC

  1 month

• Efficacy of at least 1 dose of CART-33

  6 months

• Overall Survival (OS)

  6 months, 12 months

• Progression free survival (PFS)

  6 months, 12 months

• Duration of Response (DOR)

  15 years

Study Arms (1)

CD33KO-HSPC followed by CART33

EXPERIMENTAL

All subjects will receive CD33KO-HSPC, followed by 1-3 CART-33 infusions

Biological: CD33KO-HSPC; CART33

Interventions

CD33KO-HSPC; CART33 BIOLOGICAL

CD33KO-HSPC: Stem cell transplant (also known as bone marrow transplant) is a common treatment used for patients with blood cancers, but for this transplant we will first modify the cells, in order to make the CAR T-cell treatment safer for when the patient receives them later. The modification is a type of gene editing - this means changing the DNA of the cells, so that a protein that the bone marrow stem cells usually show on their surface is not shown any more. This makes the bone marrow cells "invisible" to the CAR T-cells, and makes this therapy safer for the patient. The protein is called CD33. CART33: Chimeric Antigen Receptor T-cells (CART) are immune cells which are modified by adding a CAR molecule, which makes them much more efficient at finding and killing cancer cells. In this case, the CAR T-cells are programmed to target a protein called CD33, which is found on the surface of leukemia cells, and on healthy bone marrow cells.

CD33KO-HSPC followed by CART33

Eligibility Criteria

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

You may qualify if:

• Male or female 18 years of age or older
• Subjects with AML unlikely to be cured with currently available therapies
• AML that has not achieved a complete remission or morphologic leukemia free state by ELN criteria; partial remission or refractory disease (including primary refractory) are eligible; 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 HCT is eligible; OR:
• Subjects with relapsed disease after prior transplant must be off systemic immunosuppression for at least 1 month at the time of enrollment.
• Subjects must have a suitable stem cell donor.
• Satisfactory organ function
• Creatinine clearance \> 40 ml/min
• ALT/AST must be ≤ 5x upper limit of normal unless related to disease and \< 20 x upper limit of normal if related to disease
• Direct bilirubin \< 2.0 mg/dl, unless subject has Gilbert's syndrome (≤ 3.0 mg/dL)
• Left ventricular ejection fraction ≥ 40% as confirmed by echocardiogram or MUGA
• DLCO \> 45% predicted
• ECOG performance status 0-1
• Written informed consent is given
• Subjects of reproductive potential must agree to use acceptable birth control methods

You may not qualify if:

• Pregnant or lactating (nursing) women
• Active hepatitis B or hepatitis C or HIV infection
• Concurrent use of systemic steroids or immunosuppressant medications
• Any uncontrolled active medical disorder that would preclude participation as outlined
• Subjects with signs or symptoms indicative of CNS involvement.
• Known history of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)
• Class III/IV cardiovascular disability according to New York Heart Association Classification
• Subjects with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the central nervous system, and unrelated to leukemia or previous leukemia treatment.
• Subjects with clinically apparent arrhythmia, or arrhythmias that are not stable on medical management, within 2 weeks of the screening/enrollment visit.

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Noelle Frey, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abramson Cancer Center Clinical Trials Service

CONTACT

215-349-8245; PMCancerResearch@pennmedicine.upenn.edu

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: July 6, 2023
• First Posted: July 14, 2023
• Study Start: February 23, 2024
• Primary Completion (Estimated): February 23, 2029
• Study Completion (Estimated): February 23, 2044
• Last Updated: June 29, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)