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

NCT ID: NCT05945849

Last Updated: 2025-06-29

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-23
• Study Completion Date: 2044-02-23

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

CD33KO-HSPC followed by CART33

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

Group Type: EXPERIMENTAL

CD33KO-HSPC; CART33

Intervention Type: 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.

Interventions

CD33KO-HSPC; CART33

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Male or female 18 years of age or older

2. Subjects with AML unlikely to be cured with currently available therapies

1. 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:

2. 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:

3. Subjects with relapsed disease after prior transplant must be off systemic immunosuppression for at least 1 month at the time of enrollment.

3. Subjects must have a suitable stem cell donor.

4. Satisfactory organ function

1. Creatinine clearance > 40 ml/min

2. ALT/AST must be ≤ 5x upper limit of normal unless related to disease and < 20 x upper limit of normal if related to disease

3. Direct bilirubin < 2.0 mg/dl, unless subject has Gilbert's syndrome (≤ 3.0 mg/dL)

5. Left ventricular ejection fraction ≥ 40% as confirmed by echocardiogram or MUGA

6. DLCO > 45% predicted

7. ECOG performance status 0-1

8. Written informed consent is given

9. Subjects of reproductive potential must agree to use acceptable birth control methods

Exclusion Criteria

1. Pregnant or lactating (nursing) women

2. Active hepatitis B or hepatitis C or HIV infection

3. Concurrent use of systemic steroids or immunosuppressant medications

4. Any uncontrolled active medical disorder that would preclude participation as outlined

5. Subjects with signs or symptoms indicative of CNS involvement.

6. Known history of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40)

7. Class III/IV cardiovascular disability according to New York Heart Association Classification

8. 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.

9. Subjects with clinically apparent arrhythmia, or arrhythmias that are not stable on medical management, within 2 weeks of the screening/enrollment visit.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Noelle Frey, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Abramson Cancer Center Clinical Trials Service

Role: CONTACT

PMCancerResearch@pennmedicine.upenn.edu

215-349-8245

Facility Contacts

Abramson Cancer Center Clinical Trials Service

Role: primary

PMCancerResearch@pennmedicine.upenn.edu

215-349-8245

Other Identifiers

IRB # 854325, UPCC # 26423

Identifier Type: -

Identifier Source: org_study_id