Using CD22 CAR T Cells after CD19 CAR T Cells for B Cell Leukemia
Phase I/Ib Clinical Trial of Autologous CD22 Chimeric Antigen Receptor (CAR) T Cells Following Commercial CD19 CAR T Cells in Children and Young Adults With Recurrent or Refractory B Cell Malignancies
This study is testing if giving CD22 CAR T-cell therapy to children and young adults with tough-to-treat B-cell leukemia after they’ve had another CAR T-cell treatment can be safe and effective.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 20 (estimated) |
| Ages | 1 Year to 25 Years |
| Sex | All |
| Sponsor | Stanford University Academic / other |
| Drugs / interventions | Chimeric Antigen Receptor, chemotherapy, CART |
| Locations | 1 site (Palo Alto, California) |
| Trial ID | NCT06408194 on ClinicalTrials.gov |
What this trial studies
This study aims to evaluate the safety and feasibility of administering CD22 Chimeric Antigen Receptor T-Cell Therapy (CART) to children and young adults with relapsed or refractory B-cell leukemia, following an infusion of the commercial CAR T-cell therapy Tisagenlecleucel. The study is divided into two phases: the first phase focuses on determining the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of CD22 CART, while the second phase assesses the feasibility of this treatment approach. Participants will be monitored for safety and clinical activity, as well as the rate of ongoing B cell aplasia after treatment.
Who should consider this trial
Good fit: Ideal candidates are children and young adults aged 1 to 25 with relapsed or refractory B-cell acute lymphoblastic leukemia who express CD19 and CD22 on their malignant cells.
Not a fit: Patients who do not express CD19 or CD22 on their cancer cells or are outside the age range may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could provide a new treatment option for children and young adults with difficult-to-treat B-cell malignancies.
How similar studies have performed: While CAR T-cell therapies have shown success in treating B-cell malignancies, this specific approach of sequentially using CD22 CART after CD19 CART is novel and has not been extensively tested.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria:
1. Diagnosis of histologically confirmed relapsed/refractory (R/R) B cell acute lymphoblastic leukemia (ALL)
2. Must be eligible to receive commercial KYMRIAH® (tisagenlecleucel) according to FDA approved package insert (refractory disease or in second or later relapse)
3. CD19 and CD22 expression must be demonstrated on malignant cells by immunohistochemistry or flow cytometry. CD19 and CD22 expression at any level of expression will be acceptable, as that is the standard for commercial KYMRIAH® (tisagenlecleucel) and the optimal level of CD22 expression is not well defined.
4. Age: ≥ 1 year of age and ≤ 25 years and 364 days of age at time of enrollment.
5. Performance Status: Participants \> 16 years of age: Karnofsky ≥ 50%; Participants ≤ 16 years of age: Lansky scale ≥ 50%.
6. Normal Organ and Marrow Function
* Absolute Neutrophil Count (ANC) ≥ 750/uL\*
* Platelet count ≥ 50,000/uL\*
* Absolute Lymphocyte Count ALC \> 150/uL\*
* Adequate renal, hepatic, pulmonary and cardiac function defined as:
* Baseline oxygen saturation \> 92% on room air
* Creatinine within ULN for age or Creatinine clearance (as estimated by Cockcroft Gault Equation) ≥ 60 mL/min
* Total bilirubin ≤ 1.5 mg/dl, except in Participants with Gilbert's syndrome. \[Elevations related to leukemia involvement of the liver will not disqualify a subject\]
* Alanine Transaminase (ALT) or Aspartate Aminotransferase (AST) ≤ 10 x ULN (except in Participants with liver involvement by leukemia)
* Cardiac ejection fraction ≥ 40%, no evidence of pericardial effusion as determined by an Echocardiogram.
* if these cytopenias are not judged by the investigator to be due to underlying disease (i.e. potentially reversible with anti-neoplastic therapy); A subject will not be excluded because of pancytopenia ≥ Grade 3 if it is due to disease, based on the results of bone marrow studies.
7. Participants with Central Nervous System (CNS) involvement or a history of CNS involvement are eligible only in the absence of neurologic symptoms that may mask or interfere with neurological assessment of toxicity
8. Participants who have undergone autologous SCT with disease progression or relapse following SCT are eligible. Participants with history of allogeneic SCT must be at least 100 days from SCT, have no evidence of Graft versus Host Disease (GvHD), and no longer taking immunosuppressive agents for at least 30 days prior to enrollment.
9. Females of child bearing potential and males of child fathering potential must be willing to practice birth control during and for 4 months post chemotherapy or for as long as Chimeric Antigen Receptor (CAR) T cells are detectable in peripheral blood.
10. Females of child bearing potential must have negative pregnancy test.
11. Must meet wash out period since prior therapies according to commercial KYMRIAH® (tisagenlecleucel) SOPs.
12. Must have recovered from acute side effects from prior therapy to meet eligibility.
13. If had prior CAR therapy, will be eligible if at least 30 days has elapsed prior to apheresis.
14. Ability to give informed consent. All Participants ≥ 18 years of age must be able to give informed consent. For participants \<18 years old their legal authorized representative (LAR) (i.e. parent or guardian) must give informed consent. Pediatric participants will be included in age appropriate discussion and assent per institutional SOPs will be obtained for those \> 7 years of age, when appropriate. If a minor becomes of age during participation of this study, he/she will be asked to reconsent as an adult.
* A subject will not be excluded because of pancytopenia ≥ Grade 3 if it is felt by the investigator to be due to underlying disease.
Exclusion Criteria:
1. May not have Human Immunodeficiency Virus (HIV)/Hepatitis B (HBV) or Hepatitis C (HCV infection) or uncontrolled, symptomatic, intercurrent illness.
2. May not have hyperleukocytosis (≥ 50,000 blasts/μL) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy.
3. May not have severe, immediate hypersensitivity reaction attributed to compounds of similar chemical or biologic composition to any agents used in study.
4. May not have active CNS disorder, or history of MI, cardiac angioplasty or stenting, unstable angina or other clinically significant cardiac disease with 12 months of enrollment.
5. May not have primary immunodeficiency or history of autoimmune disease (e.g. Crohns, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years.
Where this trial is running
Palo Alto, California
- Stanford University — Palo Alto, California, United States (Recruiting)
Study contacts
- Study coordinator: Michelle Fujimoto
- Email: mfujimot@stanford.edu
- Phone: (650) 736-0539
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.