CD19-Car T Cell Therapy for the Treatment of Older Adults With Acute Lymphoblastic Leukemia in First Remission

NCT05707273 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 22137NCI-2022-10925P30CA033572
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial tests the safety, side effects, and best dose of autologous anti-CD19 CAR-expressing T lymphocytes (CD19-CAR T cells) in older adults with B-cell acute lymphoblastic leukemia. Chimeric antigen receptor (CAR) T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (CAR). Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of B-cell acute lymphoblastic leukemia.

Conditions

B Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (2)

• Incidence of dose-limiting toxicity (DLT)

  Assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, attribution, time of onset, duration, and reversibility or outcome.

  Up to 28 days after CD19-chimeric antigen receptor (CAR) T cell infusion

• Incidence of adverse events

  Assessed using CTCAE version 5.0. Cytokine release syndrome adverse events will be characterized using the descriptions and grading scales found in the Lee, et. al. publication: 'ASTCT Consensus Grading for Cytokine Release Syndrome and Neurologic Toxicity Associated with Immune Effector Cells. Observed toxicities will be summarized in terms of type (organ affected or laboratory determination), severity, attribution, time of onset, duration, and reversibility or outcome.

  Up to 15 years

Secondary Outcomes (6)

• Percentage of consented older B-acute lymphoblastic leukemia (ALL) patients undergoing leukapheresis who get sufficient CD19-CAR T cells manufactured and infused at their assigned dose level

  At T cell infusion (Day 0)

• Minimal residual disease (MRD) response rate

  Up to 12 months post T cell infusion

• Event-free survival

  From the start of CD19-CAR T cell infusion to the date of death or disease progression/relapse, whichever occurring first, assessed up to 15 years

• Overall survival rate

  From start of protocol therapy to death, or last follow-up, whichever comes first, assessed up to 15 years

• Rate of relapse, including MRD and extramedullary relapse

  Up to 2 years post treatment

Study Arms (1)

Treatment (CD19-CAR T cells)

EXPERIMENTAL

Patients undergo T cell leukapheresis, receive fludarabine and cyclophosphamide IV, and then receive CD19-CAR T cell infusion IV on study.

Drug: Autologous Anti-CD19 CAR-expressing T Lymphocytes; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration and Biopsy; Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Leukapheresis; Other: Questionnaire Administration

Interventions

Autologous Anti-CD19 CAR-expressing T Lymphocytes DRUG

Given IV

Also known as: Autologous Anti-CD19-CAR T Cells

Treatment (CD19-CAR T cells)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (CD19-CAR T cells)

Bone Marrow Aspiration and Biopsy PROCEDURE

Undergo bone marrow aspirate

Treatment (CD19-CAR T cells)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (CD19-CAR T cells)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (CD19-CAR T cells)

Leukapheresis PROCEDURE

Undergo T-cell leukapheresis

Also known as: Leukocytopheresis, Therapeutic Leukopheresis

Treatment (CD19-CAR T cells)

Questionnaire Administration OTHER

Complete questionnaires

Treatment (CD19-CAR T cells)

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented informed consent of the participant
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with Study Principal Investigator (PI) approval
• Note: For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated full consent is processed. However, the research participant is allowed to proceed with lymphodepletion and T cell infusion only after the translated full consent form is signed
• Age: \>= 55 years
• Eastern Cooperative Oncology Group (ECOG) \< 2 / Karnofsky Performance Status (KPS) \>= 70
• Ability to read and understand English for Questionnaires
• Histologically confirmed CD19+ ALL at the time of diagnosis
• In morphological first complete remission regardless of minimal residual disease (MRD) status
• No immediate plan for transplant
• Remission after induction +/- reinduction therapy
• Fully recovered from the acute toxic effects (except alopecia) to =\< Grade 1 to prior anti-cancer therapy
• Total bilirubin =\< 1.5 X upper limit of normal (ULN) (unless has Gilbert's disease)
• Aspartate aminotransferase (AST) =\< 3 x ULN
• Alanine transaminase (ALT) =\< 3 x ULN

You may not qualify if:

• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent(s)
• Research participant with known CNS-2 or CNS-3 involvement that is refractory to intrathecal chemotherapy and/or cranio-spinal radiation. Research participants with a history of central nervous system (CNS) disease that has been effectively treated to complete remission (\<5 WBC/mm3 and no blasts in cerebrospinal fluid \[CSF\]) will be eligible
• Autoimmune disease or active graft versus host disease (GVHD) requiring systemic immunosuppressant therapy
• Class III/IV cardiovascular disability according to the New York Heart Association (NYHA) Classification
• History of other malignancies, except for malignancy surgically resected (or treated with other modalities) with curative intent, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; non-muscle invasive bladder cancer; malignancy treated with curative intent with no known active disease present for \>= 2 years
• Clinically significant uncontrolled illness
• Active systemic uncontrolled infection requiring antibiotics
• Known history of HIV or hepatitis B or hepatitis C infection
• Subjects who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR) result. Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded
• Subjects who are hepatitis B core antibody positive (or have a known history of HBV infection) should be monitored quarterly with a quantitative PCR test for HBV deoxyribonucleic acid (DNA). HBV monitoring should last until 12 months after last dose of study drug. Any subject with a rising viral load (above lower limit of detection) should discontinue study drug and have antiviral therapy instituted and a consultation with a physician with expertise in managing hepatitis B. Subjects who are core Ab positive at study enrollment are strongly recommended to start Entecavir before start and until completion of study treatment
• Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded
• Females only: Pregnant or breastfeeding
• Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
• Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Burkitt Lymphoma

Interventions

Specimen Handling; Biopsy; Cyclophosphamide; fludarabine; Leukapheresis

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation

Study Officials

• Ibrahim Aldoss

  City of Hope Medical Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2023
• First Posted: January 31, 2023
• Study Start: April 26, 2023
• Primary Completion (Estimated): July 24, 2026
• Study Completion (Estimated): July 24, 2026
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

US (1)