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

Phase 1

Recruiting

• Conditions: Leukemia, Myeloid, Acute
• Interventions: Biological: CD33KO-HSPC; CART33

• Registration Number: NCT05945849
• Lead Sponsor: University of Pennsylvania

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-07-06
• Study First Submitted QC: 2023-07-06
• Study First Posted: 2023-07-14
• Study Start: 2024-02-23
• Status Verified: 2024-08
• Last Update Submitted: 2024-08-21
• Last Update Posted: 2024-08-22
• Primary Completion: 2029-02-23
• Study Completion: 2044-02-23

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 16

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
CD33KO-HSPC followed by CART33	CD33KO-HSPC; CART33	All subjects will receive CD33KO-HSPC, followed by 1-3 CART-33 infusions

Primary Outcome Measures

Name	Time	Method
Occurrence of dose-limiting toxicities related to CD33KO-HSPC	3 months	Safety of alloHSCT: occurrence of dose-limiting toxicities related to CD33KO-HSPC
Manufacturing feasibility	1 month	Proportion of subjects whose Product 1 (CD33KO-HSPC) meets release criteria.
Occurrence of dose-limiting toxicities related to CART-33	6 months	Safety of CART-33: occurrence of dose-limiting toxicities related to CART-33

Secondary Outcome Measures

Name	Time	Method
Efficacy of CD33KO-HSPC	1 month	Proportion of subjects with hematopoietic engraftment according to standard criteria
Efficacy of at least 1 dose of CART-33	6 months	Proportion of subjects with residual or recurrent AML before CART-33 infusion who attain a clinical response
Overall Survival (OS)	6 months, 12 months	Proportion of patients who are alive at 6 months and at 12 months
Duration of Response (DOR)	15 years	Median number of months in remission. Median time to relapse in patients who receive CART-33 and attain a response.
Progression free survival (PFS)	6 months, 12 months	Proportion of patients who remained in response at 6 and 12 months after attaining a response to the first CART-33 infusion. Median time to progression of AML from infusion of CART-33.

Trial Locations

Locations (1)

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States