Phase 2 Study of Humanized CD19-directed Chimeric Antigen Receptor-modified T Cells (huCART19) for Very High-Risk Subsets of B Cell Acute Lymphoblastic Leukemia (B-ALL)
Overview
- Phase
- Phase 2
- Intervention
- huCART19
- Conditions
- Not specified
- Sponsor
- University of Pennsylvania
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- Number of Subjects With Event-Free Survival in Patients With Newly Diagnosed VHR B-ALL or High-risk Relapse of B-ALL 1 Year After Treatment.
- Status
- Completed
- Last Updated
- 11 months ago
Overview
Brief Summary
This is a phase 2 study to evaluate humanized CD19 redirected autologous T cells (or huCART19 cells) with CD19 expressing relapsed and refractory B-cell acute lymphoblastic leukemia. This study is targeting pediatric and young adult patients aged 3 months - 29 years with CD19+ B cell malignancies in newly diagnosed B-ALL patients predicted to have an exceedingly poor outcome with conventional chemotherapy, in high-risk first relapse, or and in second or greater relapse in this phase 2 trial. In addition, a second cohort will test the efficacy of huCART19 in patients with poor response to prior B cell directed engineered cell therapy.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed informed consent form must be obtained.
- •Relapsed or refractory B-cell ALL:
- •a. Cohort A: Patients with newly diagnosed VHR B-ALL or high-risk relapse of B-ALL who meet one of the following criteria:
- •i. Newly diagnosed NCI HR B-ALL with induction failure: M3 marrow (\>25% blasts) at end of induction OR
- •ii. First marrow relapse of B-ALL at \< 36 months from diagnosis OR iii. 2nd or greater relapse OR
- •iv. Any relapse after allogeneic HSCT and ≥ 4 months from SCT at enrollment OR
- •v. Refractory disease defined as having not achieved an MRD-negative and/or CSF-negative CR after ≥ 2 chemotherapy regimens/cycles of frontline therapy or 1 cycle of reinduction therapy for patients in first relapse OR
- •vi. Ineligible for allogeneic SCT because of:
- •Comorbid disease
- •Other contraindications to allogeneic SCT conditioning regimen
Exclusion Criteria
- •Active hepatitis B or active hepatitis C.
- •HIV Infection.
- •Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy.
- •Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well.
- •CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
- •Pregnant or nursing (lactating) women.
- •Uncontrolled active infection.
- •Active medical disorder that, in the opinion of the investigator, would substantially increase the risk of uncontrollable CRS or neurotoxicity.
Arms & Interventions
Newly Diagnosed VHR B-ALL or High-Risk Relapse of B
Intervention: huCART19
Poor Response to Prior B Cell Directed Engineered cell therapy
Intervention: huCART19
Outcomes
Primary Outcomes
Number of Subjects With Event-Free Survival in Patients With Newly Diagnosed VHR B-ALL or High-risk Relapse of B-ALL 1 Year After Treatment.
Time Frame: 1 year
Time from infusion to the first of event or censoring Events = Relapse, No Response, or Death; Censoring =Initiation of New Anticancer Therapy, Last Day of Follow-up/EOS; whichever occurs first.
Number of Subjects With Event-Free Survival in Patients With Poor Response to Prior B Cell Directed Engineered Cell Therapy 1 Year After Treatment.
Time Frame: 1 year
Time from infusion to the first of event or censoring Events = Relapse, No Response (including CR/CRi without B Cell Aplasia), or Death; Censoring =Initiation of New Anticancer Therapy, Last Day of Follow-up/EOS; whichever occurs first.
Secondary Outcomes
- Overall Remission Rate(28 Days)
- Overall Remission Rate (Cohort B)(28 Days)
- Percentage of Subjects With Relapse-free Survival(1 year)