Pediatric Cancers
Phase I Study of T Cells Expressing an Anti-CD19 Chimeric Receptor in Children and Young Adults With B Cell Malignancies
NCI-12-C-0112, NCT01593696
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Investigator(s): |
Alan S. Wayne, M.D.
Principal Investigator
Phone: 301-496-4256
Fax: 301-451-7010
waynea@mail.nih.gov
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Pediatric Oncology
Phone: 301-496-4256
1-877-624-4878 (Toll free)
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Background:
- Chimeric antigen receptors (CAR) that recognize the CD19 antigen have been constructed and are in clinical trials at several institutions; in this trial, the POB will utilize a chimeric receptor containing the signaling domains of CD28 and CD3-zeta, currently under study in the CCR in adults, for children and young adults with CD19-expressing malignancies
- Anti-CD19-CAR transduced T cells show robust killing in co-cultures with CD19-expressing acute lymphoblastic leukemia cells (ALL), and in xenograft models, can rapidly clear CD19-expressing ALL cell lines
Objectives:
- Primary Objectives:
- Determine the safety and feasibility of administering escalating doses of anti-CD19-CAR-engineered peripheral blood lymphocytes in two strata (prior allogeneic stem cell transplant [SCT] vs. no prior SCT) of children and young adults with B cell malignancies following a cyclophosphamide/fludarabine preparative regimen
- Secondary Objectives:
- Determine if the administration of anti-CD19-CAR-engineered peripheral blood lymphocytes can mediate antitumor effects in children with B cell malignancies
- Measure persistence of adoptively-transferred anti-CD19-CAR-transduced T cells in the blood and CSF of patients
Key Eligibility Criteria:
- Diagnosis of a CD19-expressing B-cell malignancy that has recurred after or not responded to at least one standard and one salvage chemotherapy-containing regimen for the malignancy and is deemed incurable by standard therapy
- 1-21 years of age
- ≥ 15 kg
- Adequate organ function
- Patients with a history of allogeneic SCT who meet all eligibility criteria are eligible to participate
Study Outline:
- PBMC will be obtained by leukapheresis, CD3+ cells will be cultured in the presence of anti-CD3/-CD28 beads, followed by retroviral vector supernatant containing the anti-CD19 CAR; total culture time is 11-13 days
- On Day -4, patients will begin chemotherapy comprising fludarabine 25 mg/m2 on Days -4, -3, and -2 and cyclophosphamide 900 mg/m2 on Day -2
- The CD19-CAR cells will be infused on Day 0, with up to a 48 hour delay allowed if needed for resolution of clinical toxicities related to chemotherapy or to generate adequate cell numbers
- A phase I cell dose escalation scheme will be performed using three dose levels (1 x 106 transduced T cells/kg; 3 x 106 transduced T cells/kg; 1 x 107 transduced T cells/kg) in two strata: patients who have undergone prior SCT and patients who have not previously undergone SCT
- Three patients will be enrolled at each dose level, with the cohort expanded to six if dose limiting toxicity (DLT) occurs; if a cohort of patients previously treated with prior SCT completes a dose level without DLT, patients in the other stratum (without previous SCT) may dose escalate simultaneously
- An expanded group of 12 patients at the maximum tolerated dose (MTD)—or the highest dose achieved if no MTD was determined—will be accrued to provide additional information regarding the feasibility, safety and efficacy of this treatment
- Patients will be monitored for toxicity, response, and T cell persistence
Additional Information:
- This trial will be conducted at the NIH Clinical Center in Bethesda, MD. It is open to patients who meet the eligibility requirements, regardless of where they live in the United States.
- There is no charge for medical care received at NIH Clinical Center.
- PDQ (Physicians Data Query) - provides additional details about this study for health care providers.
Reviewed: 12/14/12
Updated: 6/5/12
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