CD22 Redirected Autologous T Cells for ALL

Launched by UNIVERSITY OF PENNSYLVANIA · Jan 7, 2016

Keywords

ClinConnect Summary

This clinical trial, called "CD22 Redirected Autologous T Cells for ALL," is exploring a new treatment option for children and young adults with specific types of leukemia, particularly those who have not responded to previous treatments. The study is testing a single dose of specially modified immune cells (T cells) that are designed to target and attack leukemia cells expressing a protein called CD22. The goal is to determine if this treatment is safe and feasible for patients with relapsed or hard-to-treat B cell acute lymphoblastic leukemia.

To be eligible for this trial, participants must be between 1 and 29 years old and have a documented history of relapsed or refractory B cell leukemia. They will need to show that their cancer cells express the CD22 protein and meet certain health criteria, such as having adequate organ function. Interested individuals or their guardians will need to provide informed consent before participating. If enrolled, participants can expect close monitoring during the trial to assess the safety and effectiveness of this new treatment. It’s important to note that certain medical conditions, such as active infections or specific health issues, may exclude someone from participating in the study.

Gender

ALL

Eligibility criteria

• • 1. Signed informed consent form must be obtained prior to any study procedure.
• 2. Relapsed or refractory B-cell ALL:
• • 1. 2nd or greater relapse OR
• • 2. Any marrow or extramedullary relapse after allogeneic HSCT and ≥ 6 months from SCT at infusion OR
• • 3. Any marrow relapse after CAR-modified T cell therapy OR
• • 4. Refractory disease defined as having not achieved a CR after \> 2 chemotherapy regimens OR
• • 5. Patients with Ph+ ALL are eligible if they are intolerant to or have failed tyrosine kinase inhibitor therapy OR
• 6. Ineligible for allogeneic SCT because of:
• • i. Comorbid disease ii. Other contraindications to allogeneic SCT conditioning regimen iii. Lack of suitable donor iv. Prior SCT v. Declines allogeneic SCT as a therapeutic option after documented discussion, with expected outcomes, about the role of SCT with a BMT physician not part of the study team g. Patients with CNS3 disease will be eligible if CNS disease is responsive to therapy (at infusion, must meet criteria in Section 5.2)
• • 3. Documentation of CD22 tumor expression in bone marrow, other tumor biopsy, CSF or peripheral blood by flow cytometry (or a recent marrow in the case of refractory disease). If the patient has received CD22-directed therapy (i.e., inotuzumab), then the marrow or other sample should be obtained after this therapy to show CD22 expression.
• 4. Adequate organ function defined as:
• a. A serum creatinine based on age/gender as follows:
• 1. A serum creatinine based on age/gender as follows:
• • Maximum Serum Creatinine (mg/dL) Age 1 to \< 2 years Male 0.6 Female 0.6 Age 2 to \< 6 years Male 0.8 Female 0.8 Age 6 to \< 10 years Male 1.0 Female 1.0 Age 10 to \< 13 years Male 1.2 Female 1.2 Age 13 to \< 16 years Male 1.5 Female 1.4 Age ≥ 16 years Male 1.7 Female 1.4
• • 2. Adequate liver function
• • i. ALT \< 500 U/L ii. Bilirubin \<3x upper limit of normal
• • iii. ALT and/or bilirubin that exceed these ranges is acceptable if, in the opinion of the investigator (or by liver biopsy), the abnormalities are directly related to ALL infiltration of the liver
• • c. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea, pulse oxygen \> 92% on room air; DLCO \> 40% (corrected for anemia) if PFTs are clinically appropriate as determined by the treating investigator
• • d. Left Ventricle Shortening Fraction (LVSF) ≥ 28% or Ejection Fraction (LVEF) ≥ 40% confirmed by ECHO/MUGA; in cases where quantitative assessment of LVEF is not possible, a statement by the cardiologist that the ECHO shows qualitatively normal ventricular function will suffice.
• • 5. Evidence of disease by standard morphologic or by MRD criteria. If the results of a historical biopsy (obtained at the time of the patient's most recent relapse) are available, this does not need to be repeated at screening.
• • 6. Age 1-29 years.
• • 7. Adequate performance status (Lansky or Karnofsky score ≥50).
• • 8. Subjects of reproductive potential must agree to use acceptable birth control methods.
• Exclusion Criteria:
• • 1. Active hepatitis B or active hepatitis C.
• • 2. HIV Infection.
• • 3. Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy.
• • 4. Concurrent use of systemic steroids or immunosuppressant medications. Recent or current use of inhaled steroids or physiologic replacement with hydrocortisone is not exclusionary.
• • 5. CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
• • 6. Pregnant or nursing (lactating) women.
• • 7. Receipt of a prior investigational study agent within 4 weeks prior to screening visit. \*Note - patients who have received anti-CD19 CART cells (e.g., CART19/CTL019) on an investigational study where cell infusion occurred greater than 4 weeks before the screening visit are NOT excluded.