CD19-CD22-Bispecific Chimeric Antigen Receptor (CAR) T Cell Therapy for Pediatric Patients With Acute Lymphoblastic Leukemia
Purpose
This study is a phase I study designed to evaluate the safety of CD19-CD22-CAR T cells. Primary Objective: To determine the safety profile and propose the recommended phase 2 dose (RP2D) of autologous CD19-CD22-CAR T cells in patients ≤ 21 years of age with recurrent/refractory CD19- and/or CD22-positive leukemia. Secondary Objective: To evaluate the anti-leukemic activity of CD19-CD22-CAR T cells.
Conditions
- Acute Lymphoblastic Leukemia
- Recurrent Acute Lymphoblastic Leukemia
- Recurrent B Acute Lymphoblastic Leukemia
Eligibility
- Eligible Ages
- Under 21 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Age <21 years old - Relapsed/refractory CD19- and/or CD22-positive acute leukemia defined as: *CD19 and/or CD22-positivity confirmed within 2 months and after receipt of any CD19 or CD22-directed therapy - Second or greater relapse - Any relapse after allogeneic HCT - Refractory disease (primary or in relapse) despite therapy designed to induce remission - Estimated life expectancy of > 12 weeks - Karnofsky or Lansky (age-dependent) performance score ≥50 (Appendix A) - For females of childbearing age: - Not lactating with intent to breastfeed - Not pregnant with negative serum or urine pregnancy test within 7 days prior to enrollment
Exclusion Criteria
- Known primary immunodeficiency - Known HIV positivity - Known contraindication to receiving protocol defined lymphodepleting - chemotherapy regimen - History of hypersensitivity reaction to murine protein-containing products Treatment Eligibility Inclusion Criteria: - Age < 21 years old - Detectable disease in the bone marrow - Estimated life expectancy of > 8 weeks - Karnofsky or Lansky (age-dependent) performance score > 50 (Appendix A) - Adequate cardiac function defined as left ventricular ejection fraction >40%, or shortening fraction > 25% - EKG without evidence of clinically significant arrhythmia - Adequate renal function defined as creatinine clearance or radioisotope GFR >50 mL/min/1.73m2 (GFR >40 mL/min/1.73m2 if <2 years of age) - Adequate pulmonary function defined as forced vital capacity (FVC) >50% of predicted value; or pulse oximetry >92% on room air - Total bilirubin < 3 times the upper limit of normal for age, except in subjects with Gilbert's syndrome - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 5 times the upper limit of normal for age - Has recovered from all NCI CTAE grade III-IV, non-hematologic acute toxicities from prior therapy - Prior to planned CAR T cell infusion, patients with a history of prior allogeneicHCT must be at least 3 months from HCT, have no evidence of acute GVHD, and have not received a donor lymphocyte infusion (DLI) within the 28 daysprior to planned infusion - For females of childbearing age: - Not lactating with intent to breastfeed - Not pregnant with negative serum or urine pregnancy test within 7 days prior to enrollment - If sexually active, agreement to use birth control until 3 months after T cell infusion. Male partners should use a condom. Exclusion Criteria: - Known primary immunodeficiency - Known HIV positivity - Known contraindication to receiving protocol defined lymphodepleting - chemotherapy regimen - History of hypersensitivity reactions to murine protein-containing products - Severe, uncontrolled bacterial, viral or fungal infection - Active CNS-3 disease - Evidence of active, uncontrolled neurologic disease
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Single Group Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental CD19-CD22-CAR T cell therapy |
This study has two parts: Collection and Manufacturing Phase - Patients will have white blood cells collected in the St. Jude Blood Donor Center through a procedure called apheresis, or your doctors may use a previously collected frozen product. The collected cells will be engineered to improve their ability to recognize and kill cancer cells. The final cell product is referred to as the CD19-CD22 CAR T cells. Treatment Phase - Eligible patients will receive chemotherapy before receiving the CAR T cells. |
|
Recruiting Locations
St. Jude Children's Research Hospital
Memphis 4641239, Tennessee 4662168 38105
Memphis 4641239, Tennessee 4662168 38105
More Details
- Status
- Recruiting
- Sponsor
- St. Jude Children's Research Hospital
Detailed Description
Treatment will include a single course of lymphodepleting chemotherapy (fludarabine/cyclophosphamide) followed by CAR T cell infusion. CAR T cell dose will be determined by the protocol-defined dose escalation scheme, based on the number of CAR+ T cells and participant weight.