New treatment combining stem cell transplant and CAR T-cell therapy for acute leukemia

Phase 1 Study of Lentivirally Transduced T Cells Engineered to Contain Anti-CD33 Linked to TCRζ And 4-1BB Signaling Domains In Combination With CD33KO-HSPC In Subjects With Refractory Or Relapsed Acute Myeloid Leukemia

This study is testing a new treatment that combines a stem cell transplant with special CAR T-cells to see if it can help people with hard-to-treat acute myeloid leukemia.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of Pennsylvania (Academic / other)
• Drugs / interventions: CAR T, chimeric antigen receptor
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT05945849 on ClinicalTrials.gov

What this trial studies

This study aims to develop a novel treatment for acute myeloid leukemia (AML) by combining a modified stem cell transplant with engineered CAR T-cells that target AML cells. The approach involves infusing blood-forming stem cells from a healthy donor, followed by CAR T-cells that are designed to attack leukemia cells while avoiding damage to the transplanted healthy cells. This innovative method seeks to enhance the effectiveness of treatment for patients with refractory or relapsed AML who have limited options available.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with AML that is unlikely to be cured by existing therapies.

Not a fit: Patients who have achieved complete remission or have AML that is easily treatable with current therapies may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new hope for patients with refractory or relapsed AML, potentially improving their chances of remission.

How similar studies have performed: Other studies have shown promise with similar approaches, but this specific combination of therapies is relatively novel.

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.

Where this trial is running

Philadelphia, Pennsylvania

• University of Pennsylvania — Philadelphia, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Noelle Frey, MD — University of Pennsylvania
• Study coordinator: Abramson Cancer Center Clinical Trials Service

Conditions Leukemia, Myeloid, Acute