Status:
RECRUITING
Study of CD19-directed Allogeneic Memory T-cell Therapy for Relapsed/Refractory CD19+ Leukemia
Lead Sponsor:
St. Jude Children's Research Hospital
Conditions:
Acute Lymphoblastic Leukemia, in Relapse
Acute Lymphoblastic Leukemia, Refractory
Eligibility:
All Genders
Up to 21 years
Phase:
PHASE1
Brief Summary
This is a Phase I clinical study evaluating the safety and maximum tolerated dose of a novel CAR T-cell product: allogeneic memory (CD45RA- negative) T-cells expressing a CD19-specific CAR 41BBz (CD19...
Detailed Description
This is a Phase I dose escalation study using a 3+3 study design. Two groups of patients will be evaluated in this study: group A - patients have received a prior stem cell transplant from their CAR T...
Eligibility Criteria
Inclusion
- Inclusion Criteria Eligibility Criteria for Donors: Apheresis and Manufacturing
- Age ≥ 18 years old
- At least single haplotype matched (≥ 3/6) family member
- HIV negative
- For females of child bearing age: Not pregnant as confirmed by negative serum or urine pregnancy test within 14 days prior to enrollment AND Not lactating with intent to breastfeed
- Completed the process of donor eligibility determination as outlined in 21 CFR 1271 and agency guidance
- For Cohort A only, identified recipient with relapsed and/or refractory CD19-positive leukemia
- For Cohort B only, iIdentified recipient with relapsed and/or refractory CD19-positive leukemia who is not suitable to receive autologous CD19-CAR T-cell therapy as defined by the following:
- Relapsed and/or refractory disease despite prior treatment with autologous CD19- CAR T-cell therapy
- History of prior autologous leukapheresis failure
- History of prior autologous CAR T-cell manufacturing failure
- Unable to undergo autologous leukapheresis in the opinion of the study PI(s): examples may include - patient small size/low weight, inadequate T-cell counts, rapidly progressive leukemia, clinical status not amenable to apheresis
- Eligibility Criteria for Patients: Treatment
- Age ≤ 21 years old
- Relapsed and/or refractory CD19-positive leukemia\*:
- Refractory disease (defined as any of the following):
- Primary refractory disease despite at least 2 cycles of an intensive chemotherapy regimen designed to induce remission
- Refractory disease despite salvage therapy
- Relapsed disease (defined as any of the following):
- 2nd or greater relapse
- Any relapse after allogeneic hematopoietic cell transplantation (HCT)
- 1st relapse if patient requires an allogeneic HCT as part of standard of care relapse therapy, but is found to be ineligible and/or unsuitable for HCT
- CD19-positivity confirmed within 2 months and after receipt of any CD19-directed therapy
- Patient cohorts:
- Cohort A: patient has previously received a HCT from the selected CAR T-cell donor
- Cohort B - patient has NOT previously received a HCT from the selected CAR T-cell donor.
- For Cohort B only, not suitable to receive autologous CD19-CAR T-cell therapy as defined above in Criteria: Eligibility Criteria for Donors: Apheresis and Manufacturing
- Detectable medullary CD19-positive leukemia
- Estimated life expectancy of ≥ 8 weeks
- Karnofsky or Lansky performance score ≥ 50
- No CNS-3 disease or any level of detectable leukemia in CNS with associated neurologic symptoms
- If history of allogeneic HCT (regardless of donor type), prior to planned CAR T-cell infusion, must meet the following criteria:
- ≥ 3 months from HCT
- have recovered from prior HCT therapy
- have no evidence of active GVHD within prior 2 months
- have not received a donor lymphocyte infusion (DLI) within the 28 days prior to planned CAR T-cell infusion
- Adequate cardiac function: left ventricular ejection fraction ≥ 40% or shortening fraction ≥ 25% (function may be supported by pharmacologic therapy)
- EKG without evidence of clinically significant arrhythmia
- Adequate renal function: creatinine clearance or radioisotope GFR 50 ml/min/1.73m2 (GFR 40 ml/min/1.73m2 if \< 2 years of age)
- Adequate pulmonary function: forced vital capacity (FVC) ≥ 50% of predicted value; or pulse oximetry ≥ 92% on room air if patient is unable to perform pulmonary function testing
- 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
- No history of HIV infection
- No evidence of severe, uncontrolled bacterial, viral or fungal infection
- Has recovered from all NCI CTAE grade III-IV, non-hematologic acute toxicities from prior therapy
- For females of child bearing age:
- Not pregnant with negative serum or urine pregnancy test ≤ 7 days prior to enrollment AND Not lactating with intent to breastfeed
- If sexually active, agreement to use birth control until 6 months after CAR T-cell infusion
- No history of hypersensitivity reactions to murine protein-containing products
- Not receiving systemic steroids therapy exceeding the equivalent of 0.5 mg/kg/day of methylprednisolone ≤ 7 days prior to CAR T-cell infusion
- Not receiving systemic therapy ≤ 14 days prior to CAR T-cell infusion, which will interfere with the activity of the CAR T-cell product in vivo (in the opinion of the study PI(s))
- Not receiving intrathecal chemotherapy ≤ 7 days prior to CAR T-cell infusion
- Exclusion Criteria:
- NA
Exclusion
Key Trial Info
Start Date :
February 14 2024
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
July 1 2028
Estimated Enrollment :
60 Patients enrolled
Trial Details
Trial ID
NCT04881240
Start Date
February 14 2024
End Date
July 1 2028
Last Update
December 23 2025
Active Locations (1)
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1
St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105