Phase I CD19/CD22 Chimeric Antigen Receptor T Cells in Peds Recurrent/Refractory B Cell Malignancies
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|ClinicalTrials.gov Identifier: NCT03241940|
Recruitment Status : Recruiting
First Posted : August 8, 2017
Last Update Posted : August 29, 2019
|Condition or disease||Intervention/treatment||Phase|
|B Acute Lymphoblastic Leukemia CD19 Positive Minimal Residual Disease Philadelphia Chromosome Positive Recurrent Adult Acute Lymphoblastic Leukemia Recurrent Childhood Acute Lymphoblastic Leukemia Refractory Acute Lymphoblastic Leukemia||Biological: Chimeric Antigen Receptor T-Cell Therapy Drug: Cyclophosphamide Drug: Fludarabine Phosphate Other: Laboratory Biomarker Analysis Other: Questionnaire Administration||Phase 1|
I. Determine the feasibility of producing CD19/CD22-CAR T cells meeting the established release criteria.
II.Assess the safety of administering escalating doses of autologous CD19/CD22-CAR T cells that meet established release specifications in children and young adults with B-cell hematologic malignancies following a cyclophosphamide/fludarabine conditioning regimen. The following dose escalation will be used in two disease groups: 1) children and young adults with relapsed/refractory low disease burden ALL (< 5% blasts), and 2) children and young adults with relapsed/refractory high disease burden ALL (≥5% blasts) or lymphoma:
- Dose Level -1: 3 x 105 transduced T cells/kg (± 20%)
- Dose Level 1: 1 x 106 transduced T cells/kg (± 20%)
- Dose Level 2: 3 x 106 transduced T cells/kg (± 20%)
- Dose Level 3: 1 x 107 transduced T cells/kg (± 20%)
I. Evaluate the ability of CD19/CD22-CAR T cells to mediate clinical activity in children and young adults with B-acute lymphoblastic leukemia (ALL).
I. Analyze alterations in early B cell development induced by immune pressure exerted via CD19/CD22-CAR T cells.
II. Evaluate whether subjects receiving CD19/CD22-CAR T cells relapse with loss or diminished expression of CD19 and/or CD22, when feasible.
III. Measure persistence of CD19/CD22-CAR T cells in the blood, bone marrow and cerebral spinal fluid (CSF), and explore correlations between CD19/CD22-CAR T cell properties and CAR T cell efficacy and persistence.
IV. Establish the utility of chromatin structure and epigenomic technology to characterize CAR T cell therapies.
V. Explore the ability of CD19/CD22-CAR T cells to mediate clinical activity in children and young adults with refractory B cell lymphoma in a non-statistical cohort due to expectations of low accrual.
OUTLINE: This is a dose-escalation study of CD19/CD22-CAR T cells.
Patients receive fludarabine phosphate intravenously (IV) over 30 minutes on days -4 to -2 and cyclophosphamide IV over 60 minutes on day -2. Patients then receive CD19/CD22-CAR T cells IV over 10-20 minutes on day 0. Patients that benefited from the first dose of CD19/CD22-CAR T cells, had no unacceptable side effects, and have enough cells left over may receive 2 or 3 additional doses of CD19/CD22-CAR T cells.
After completion of study treatment, patients are followed up daily until day 14, twice weekly until day 28, at 2 and 3 months, every 3 months until month 12, every 6-12 months up to year 5, and then annually for years 6-15.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase I Dose Escalation Study of CD19/CD22 Chimeric Antigen Receptor (CAR) T Cells in Children and Young Adults With Recurrent or Refractory B Cell Malignancies|
|Actual Study Start Date :||October 20, 2017|
|Estimated Primary Completion Date :||August 1, 2025|
|Estimated Study Completion Date :||August 1, 2035|
Experimental: Treatment (CD19/CD22-CAR T cells, chemotherapy)
Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and cyclophosphamide IV over 60 minutes on day -2. Patients then receive CD19/CD22-CAR T cells IV over 10-20 minutes on day 0. Patients that benefited from the first dose of CD19/CD22-CAR T cells, had no unacceptable side effects, and have enough cells left over may receive 2 or 3 additional doses of CD19/CD22-CAR T cells.
Biological: Chimeric Antigen Receptor T-Cell Therapy
Given CD19/CD22-CAR T cells IV
Other Name: CAR T-cell therapy
Drug: Fludarabine Phosphate
Other: Laboratory Biomarker Analysis
Other: Questionnaire Administration
- Incidence and severity of dose limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD19/CD22 chimeric antigen receptor (CAR) T cells [ Time Frame: Up to 28 days ]Will be recorded and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 at three dose levels until the maximum tolerated dose (MTD) is determined.
- Rate of successful manufacture and expansion of the CD19/CD22 chimeric antigen receptor (CAR) T cells to satisfy the targeted dose level and meet the required release specifications outlined in the Certificate of Analysis (COA) [ Time Frame: 10-14 days after apheresis or thawing of cryopreserved peripheral blood mononuclear cell ]The number of subjects which can successfully manufacture the targeted dose number will be determined for each dose cohort.
- The ability to achieve a clinical response after administration of CD19/CD22 chimeric antigen receptor (CAR) T cells [ Time Frame: Up to 15 years ]Will be assessed by the Response Criteria for Lymphoma and the Response Criteria for Acute Lymphoblastic Leukemia.
- Alterations in early B cell development induced by immune pressure exerted via CD19/CD22-CAR T cells [ Time Frame: Up to 15 years ]Will be analyzed.
- CD19/CD22 chimeric antigen receptor (CAR) T cell properties [ Time Frame: Up to 15 years ]Will explore correlations with CAR T cell efficacy and persistence.
- Frequency of CD22+ expression on lymphoma cells [ Time Frame: Up to 15 years ]Will determine site density when possible.
- Persistence of CD19/CD22 chimeric antigen receptor (CAR) T cells blood, bone marrow, and cerebral spinal fluid (CSF) [ Time Frame: Up to 15 years ]Will be measured.
- Relapse with loss or diminished expression of CD19 and/or CD22 [ Time Frame: Up to 15 years ]Will be evaluated when feasible.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03241940
|Contact: Anne Marcyfirstname.lastname@example.org|
|United States, California|
|Lucile Packard Children's Hospital Stanford University||Recruiting|
|Palo Alto, California, United States, 94304|
|Contact: Anne Marcy 650-721-9994 email@example.com|
|Principal Investigator: Crystal L. Mackall|
|Principal Investigator:||Crystal Mackall||Stanford University|