Cellular Immunotherapy in Treating Patients With High-Risk Acute Lymphoblastic Leukemia

NCT02146924 | Active Not Recruiting Phase 1 DMC

• 8 other identifiers: 13447NCI-2014-0106012020211166010963011366013447/115692118097
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial studies the side effects and best dose of cellular immunotherapy in treating patients with high-risk acute lymphoblastic leukemia. Placing a modified gene into white blood cells may help the body build an immune response to kill cancer cells.

Conditions

B Acute Lymphoblastic Leukemia; Recurrent Acute Lymphoblastic Leukemia; Refractory Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (4)

• Toxicity profile of T-cell infusion as defined by all toxicities associated with T cells at the probably or definite levels

  Assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The incidence of toxicity will also be measured according to the modified cytokine release syndrome grading as applicable. Tables will be created to summarize all toxicities and side effects by dose, time post treatment (first 28 days, days 29-60, 61-100, \> 100), organ, severity, and attribution.

  Up to 15 years

• Dose-limiting toxicity (DLT) rate at the phase II recommended dose (RP2D) (CD19R(EQ)28zeta/EGFRt+ central memory T cells)

  Assessed using CTCAE version 4.0 for Arm I. Rates and associated 95% exact Clopper-Pearson binomial confidence limits will be estimated.

  Up to 28 days

• DLT rate at RP2D assessed using CTCAE version 4.0 for Arm II (CD19R(EQ)28zeta/EGFRt+ naive and memory T cells [TN/NEM])

  Rates and associated 95% exact Clopper-Pearson binomial confidence limits will be estimated.

  Up to 28 days

• Complete response (CR) or CR with incomplete bone marrow recovery (CRi) with the exception of participants in CR or CRi that go from minimal residual disease (MRD) negative to MRD positive or progress as determined by the principal investigator

  Rates and associated 95% exact Clopper-Pearson binomial confidence limits will be estimated.

  Within the first 28 days after infusion

Secondary Outcomes (3)

• Detection of transferred T cells in the circulation for at least 28 days by quantitative-polymerase chain reaction (PCR)

  28 days

• No MRD

  Up to 15 years

• CD19 B cell aplasia/immunoglobulin G levels

  Up to 12 months

Study Arms (2)

Arm I (cellular immunotherapy closed to accrual January 2019)

EXPERIMENTAL

Patients receive lymphodepleting regimen per treating physician's discretion 3-14 days before the T-cell infusion. Patients receive CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells IV over 15 minutes on day 0. Patients who have evidence of disease, whose tumor(s) continue to express the appropriate antigen target may receive an optional second infusion of CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T cells after 28 days.

Biological: CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T-lymphocytes; Other: Laboratory Biomarker Analysis

Arm II (cellular immunotherapy)

ACTIVE COMPARATOR

Patients receive lymphodepleting regimen per treating physician's discretion 3-14 days before the T-cell infusion. Patients receive CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/nem-enriched T cells IV over 15 minutes on day 0. Patients who have evidence of disease, whose tumor(s) continue to express the appropriate antigen target may receive an optional second infusion of CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/nem-enriched T cells after 28 days.

Biological: CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes; Other: Laboratory Biomarker Analysis

Interventions

CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T-lymphocytes BIOLOGICAL

Given IV

Also known as: CD19-CAR-specific/truncated EGFR Lentiviral Vector-transduced T Cells, CD19CAR-CD28-CD3zeta-EGFRt-expressing Tcm-enriched T Cells, CD19R(EQ)28zeta/EGFRt+ TCM, CD19R(EQ)28zeta/truncated Human EGFR+ Central Memory T Cells, CD19R:CD28:lentiviral/EGFRt+ T Cells

Arm I (cellular immunotherapy closed to accrual January 2019)

CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T-lymphocytes BIOLOGICAL

Given IV

Also known as: CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem-enriched T Cells, CD19R(EQ)28zeta/EGFRt+ Naive and Memory T Cells, CD19R(EQ)28zetaEGFRt+ Tn/mem Cells

Arm II (cellular immunotherapy)

Laboratory Biomarker Analysis OTHER

Correlative studies

Arm I (cellular immunotherapy closed to accrual January 2019); Arm II (cellular immunotherapy)

Eligibility Criteria

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

You may qualify if:

• City of Hope (COH) pathology review confirms that research participant's diagnostic material is consistent with history of ALL with history of recurrence/progression/minimal residual disease (MRD) following prior therapy; additionally, CD19 positivity must be documented in a pathology report; however, it is not a requirement that the CD19 testing be performed by a COH pathologist; patients in second complete remission (CR2) or higher with history of CD19+ ALL on previous bone marrow biopsy are also eligible for the study
• Research participants with confirmed 1st or higher relapse of disease by morphology, cytogenetics or molecular, or research participants with refractory or residual disease
• Minimal residual disease (MRD) will be defined in this protocol by presence of malignant cells at 0.01% or more by flow cytometry or polymerase chain reaction (PCR) analysis at the completion of initial remission induction therapy
• Participants with central nervous system (CNS) involvement by leukemia (CNS2 and CNS3) may be considered eligible after discussions with the study team.
• Karnofsky performance status (KPS) of \>= 70%
• Life expectancy \>= 16 weeks at time of enrollment
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
• All research participants must have the ability to understand and the willingness to sign a written informed consent
• Note: For research participants who do not speak English, a short form consent may be used with a COH certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated full consent in processed; however, the research participant is allowed to proceed with lymphodepletion and T cell infusion only after the translated full consent form is signed
• PROTOCOL-SPECIFIC CRITERIA:
• COH pathology review confirms that research participant's diagnostic material is consistent with ALL; additionally, CD19 positivity must be documented in a pathology report; however it is not a requirement that the CD19 testing be performed by a COH pathologist
• Negative serum pregnancy test for women of childbearing potential
• If a research participant has undergone prior allogeneic stem cell transplant (alloSCT), and has documented =\< grade 2 graft versus host disease (GVHD) but the donor is undergoing leukapheresis, the research participant may be considered eligible for enrollment (at the discretion of the study principal investigator \[PI\]) provided that immunosuppressants can be tapered off completely prior to lymphodepletion
• If the research participant is to undergo leukapheresis, he/she must have a pretreatment calculated creatinine clearance of \>= 50 mL/minute
• If the research participant is to undergo leukapheresis, he/she must have a serum bilirubin =\< 2.0 mg/dl

You may not qualify if:

• Research participants with any uncontrolled illness including ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, poorly controlled pulmonary disease or psychiatric illness/social situations that would limit compliance with study requirements
• Research participants with known active hepatitis B or C infection; research participants who are human immunodeficiency virus (HIV) positive based on testing performed within 4 weeks of enrollment; research participants with any signs or symptoms of active infection, positive blood cultures or radiological evidence of infections
• Research participants receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy
• Note: Please note that the above criterion is not applicable at the time of enrollment if the research participant's donor is undergoing leukapheresis
• Research participants with presence of other active malignancy; however, research participants with history of prior malignancy treated with curative intent and in complete remission are eligible
• Pregnant and lactating women
• Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I study
• History or presence of clinically relevant CNS pathology such as uncontrolled seizure disorder, recent stroke, severe brain injuries, dementia, cerebellar disease or psychosis
• Any known contraindications to cyclophosphamide, fludarabine, etoposide, cetuximab or tocilizumab
• Dependence on corticosteroids
• Defined as doses of corticosteroids of greater than 5 mg/day of prednisone or equivalent doses of other corticosteroids
• Note: topical and inhaled corticosteroids in standard doses and physiologic replacement for subjects with adrenal insufficiency are allowed
• Please note that this criterion is not applicable at the time of enrollment if the research participant's donor is undergoing leukapheresis
• Active autoimmune disease requiring systemic immunosuppressive therapy
• Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

Sponsors & Collaborators

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

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Burkitt Lymphoma; Precursor Cell Lymphoblastic Leukemia-Lymphoma

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; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Study Officials

• Ibrahim Aldoss

  City of Hope Medical Center

  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: May 19, 2014
• First Posted: May 26, 2014
• Study Start: October 16, 2014
• Primary Completion (Estimated): July 15, 2026
• Study Completion (Estimated): July 15, 2026
• Last Updated: December 5, 2025

Record last verified: 2025-12

Locations

US (1)