CD22-CAR T Cells in Children and Young Adults With B Cell Malignancies

NCT04088864 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: IRB-50878CCT6003NCI-2019-07285
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is to test whether CD22-CAR T cells can be successfully made from immune cells collected from pediatric and young adult subjects with relapsed/refractory B-cell malignancies (leukemia and lymphoma). Another purpose of this study is to test the safety and cancer killing ability of a cell therapy against a new cancer target (CD22).

Conditions

B Cell Lymphoma; Acute Lymphoblastic Leukemia, Pediatric; Lymphoma

Outcome Measures

Primary Outcomes (2)

• Rate of successful manufacture of CD22 CAR T cells

  The percentage of apheresis samples (fresh or frozen) that are successfully processed and expanded to manufacture CD22 CAR T cells that satisfy the target dose level and meet release specifications will be determined for each disease group (ALL or lymphoma).

  7-11 days after apheresis

• Safe dose of CD22-CAR T cells in subjects with R/R B-cell malignancies

  Incidence and severity of dose limiting toxicities (DLTs) following chemotherapy preparative regimen and infusion of CD22 CAR T cells, as recorded and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, at target dose of 1 x 10\^6 transduced T cells/kg (± 20%).

  28 days after infusion

Secondary Outcomes (2)

• Clinical activity of CD22-CAR T cells in children and young adults with R/R CD22-expressing B-cell ALL and R/R lymphoma

  28 days after infusion of CD22-CAR T cells

• Clinical activity of CD22-CAR T cells in adults with R/R lymphoma

  3 months after infusion of CD22-CAR T cells

Study Arms (2)

R/R B-ALL

EXPERIMENTAL

Subjects will receive a conditioning lymphodepletion chemotherapy regimen of fludarabine and cyclophosphamide followed by infusion of CD22 CAR T cells on Day0. Lymphodepletion: * Fludarabine 25 mg/m2 per day IV for days 4, 3, -2 * Cyclophosphamide 900 mg/m2 per day IV on day -2 Autologous CD22 CAR T cells will be administered intravenously at Dose level 1 (1 x 10\^6 transduced T cells/kg (± 20%)).

Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Autologous CD22 CAR T

Lymphoma

EXPERIMENTAL

Subjects will receive a conditioning lymphodepletion chemotherapy regimen of fludarabine and cyclophosphamide followed by infusion of CD22 CAR T cells on Day0. Lymphodepletion: * Fludarabine 25 mg/m2 per day IV for days 4, 3, -2 * Cyclophosphamide 900 mg/m2 per day IV on day -2 Autologous CD22 CAR T cells will be administered intravenously at Dose level 1 (1 x 10\^6 transduced T cells/kg (± 20%)).

Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Autologous CD22 CAR T

Interventions

Fludarabine DRUG

Fludarabine is a purine antagonist antimetabolite

Lymphoma; R/R B-ALL

Cyclophosphamide DRUG

Cyclophosphamide is a nitrogen mustard derivative alkylating agent

Lymphoma; R/R B-ALL

Autologous CD22 CAR T DRUG

Autologous T cells transduced with lentiviral vector (m971BBZ) Chimeric Antigen Receptor (CD22 CAR)

Lymphoma; R/R B-ALL

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Disease Status Disease Status of ALL
• Must have chemotherapy refractory disease defined as progression or stable disease after two lines of therapies, or
• Relapsed disease after achieving CR.
• Subjects with persistent or relapsed minimal residual disease (MRD) (by flow cytometry, PCR, fluorescence in situ hybridization (FISH), or next generation sequencing (NGS) require verification of MRD on two occasions at least 2 weeks apart.
• Subjects with Philadelphia Chromosome positive acute lymphoblastic leukemia (Ph+ALL) subjects are eligible if they progressed, had stable disease or relapsed after two lines of therapy, including tyrosine kinase inhibitors (TKIs).
• Subjects with recurrence of isolated central nervous system CNS) relapse after achieving complete remission (CR).
• Disease Status of lymphoma
• Histologically confirmed aggressive B cell NHL including the following types defined by WHO 2008:
• \- DLBCL not otherwise specified; T cell/histiocyte rich large B cell lymphoma; DLBCL associated with chronic inflammation; Epstein Barr virus (EBV)+ DLBCL of the elderly; OR primary mediastinal (thymic) large B cell lymphoma transformation of follicular lymphoma, marginal zone lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma to DLBCL will also be included
• Subjects with DLBCL must have progressed, had SD, or recurred after initial treatment regimens that include an anthracycline and an anti CD20 monoclonal antibody. Subjects with transformed Follicular lymphoma(FL), marginal zone B-cell lymphoma (MZL), or chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) must have progressed, had SD, or recurred with transformed disease after initial treatment for DLBCL. Subjects who relapse ≥12 months after therapy should have progressed after autologous transplant or been ineligible for autologous transplant.
• Measureable Disease
• Subjects with ALL must have evaluable or measurable disease.
• Subjects with lymphoma: Must have evaluable or measurable disease according to the revisedInternational Working. Group( IWG) Response Criteria for Malignant Lymphoma. Lesions that have been previously irradiated will be considered measurable only if progression has been documented following completion of radiation therapy.
• CD22 expression
• Subjects with ALL: CD22 positive expression on malignant cells is required and must be detected by immunohistochemistry or by flow cytometry. The choice of whether to use flow cytometry or immunohistochemistry will be determined by what is the most easily available tissue sample in each subject.

You may not qualify if:

• Recurrent or refractory ALL limited to isolated testicular disease.
• Hyperleukocytosis (≥ 50,000 blasts/μL) or rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy
• History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) unless disease free for at least 3 years
• Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring IV antimicrobials for management. Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
• Ongoing infection with HIV or hepatitis B (HBsAg positive) or hepatitis C virus (anti HCV positive) as the immunosuppression contained in this study will pose unacceptable risk. A history of hepatitis B or hepatitis C is permitted if the viral load is undetectable per quantitative polymerase chain reaction (PCR) and/or nucleic acid testing.
• CNS disorder such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement hat in the judgment of the investigator may impair the ability to evaluate neurotoxicity.
• History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment.
• Any medical condition that in the judgement of the sponsor investigator is likely to interfere with assessment of safety or efficacy of study treatment
• History of severe immediate hypersensitivity reaction to any of the agents used in this study.
• Women of child bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
• In the investigators judgment, the subject is unlikely to complete all protocol required study visits or procedures, including follow up visits, or comply with the study requirements for participation
• Has primary immunodeficiency or history of autoimmune disease (e.g. Crohns, rheumatoid arthritis, systemic lupus) requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years.

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford Medical Center

Stanford, California, 94304, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Liora Schultz, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2019
• First Posted: September 13, 2019
• Study Start: January 10, 2020
• Primary Completion: October 31, 2023
• Study Completion (Estimated): September 10, 2036
• Last Updated: March 30, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)