CD123 Redirected T Cells for AML in Pediatric Subjects

Launched by UNIVERSITY OF PENNSYLVANIA · Dec 16, 2020

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment for children and young adults with relapsed or hard-to-treat Acute Myeloid Leukemia (AML). The treatment involves using specially modified immune cells, called T cells, that are designed to attack the cancer cells. This trial is in its early stages and aims to find out how safe this treatment is for young patients aged 1 to 29 who have had their leukemia return or have not responded to previous treatments.

To participate in this trial, eligible patients must have AML that has returned at least once after treatment or have leukemia that is resistant to previous therapies. They should also have a suitable donor for a stem cell transplant ready within a couple of months after receiving the treatment. Participants can expect to receive the treatment through an IV, and doctors will closely monitor their health and how well the treatment works. It’s important to know that there are specific health conditions that could prevent someone from joining, such as certain infections or severe health issues, so a thorough evaluation will take place before enrollment.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Male and female patients ≥ 1 and ≤ 29 years of age at time of consent.
• 2. AML in second or greater relapse, post-transplant relapse, or chemotherapy-refractory disease. Specifically:
• • 1. Second or greater relapse defined as flow cytometric confirmation of myeloid leukemia of at least 0.1% after second documented complete remission; OR
• • 2. Any detectable disease post-allogeneic transplant with flow cytometric confirmation (MRD) of myeloid leukemia of at least 0.1% (as confirmed by Hematologics); OR
• • 3. Refractory disease, defined as persistent bone marrow involvement with \>5% blasts after two courses of induction chemotherapy for patients at initial presentation or \>5% bone marrow blasts after one course of re-induction chemotherapy for patients who have relapsed after previously achieving a CR.
• • 3. Subjects must have a suitable stem cell donor identified with projected ability to proceed to transplant within 6-8 weeks of CART123 infusion.
• 4. Adequate organ function defined as:
• • 1. A serum creatinine based on age/gender
• • 2. Adequate liver function
• • i. ALT ≤ 5 x ULN
• • ii. Total bilirubin ≤ 3 x ULN
• • iii. ALT and/or bilirubin results that exceed this range are acceptable if, in the opinion of the physician-investigator (or as confirmed by liver biopsy), the abnormalities are directly related to AML infiltration of the liver.
• • c. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and \< Grade 3 hypoxia; DLCO ≥ 40% (corrected for anemia) if PFTs are clinically appropriate as determined by the treating investigator
• • d. Left Ventricular Shortening Fraction (LVSF) ≥ 28% or Ejection Fraction (LVEF) ≥ 45% confirmed by ECHO, or adequate ventricular function documented by a scan or a cardiologist. In cases where quantitative assessment of LVSF/LVEF is not possible, a statement by the cardiologist that the ECHO shows qualitatively normal ventricular function will suffice.
• • 5. Adequate performance status defined as Lansky or Karnofsky score ≥ 50
• • 6. Signed informed consent must be obtained.
• • 7. No contraindications for leukapheresis (unless apheresis product previously acquired).
• • 8. Subjects of reproductive potential must agree to use acceptable birth control methods.
• Exclusion Criteria:
• • 1. Pregnant or lactating (nursing) women.
• • 2. Patients with relapsed AML with t(15:17).
• • 3. Patients \< 6 months from alloHSCT.
• • 4. HIV infection.
• • 5. Active hepatitis B or hepatitis C infection.
• • 6. Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy
• • 7. Patients requiring chronic treatment with systemic steroids or immunosuppressant medications. Low-dose physiologic replacement therapy with corticosteroids, topical steroids and inhaled steroids are acceptable. For additional details regarding use of steroids and immunosuppressant medications (including washout requirements prior to CAR T cell administration).
• • 8. Any uncontrolled active medical disorder that would preclude participation as outlined.
• • 9. Uncontrolled active infection
• • 10. Subjects with CNS3 disease that is progressive on therapy or with CNS parenchymal lesions that may increase the risk of CNS toxicity. Subjects with adequately treated CNS leukemia are eligible.
• • 11. Known history of allergy or hypersensitivity to study product excipients (human serum albumin, DMSO, and Dextran 40).
• • 12. Patients with any prior history of myeloproliferative neoplasm.
• • 13. Patients with somatic JAK2 V617F mutation by PCR or next generation sequencing.