CAR-20/19-T Cells in Patients With Relapsed/Refractory B Cell ALL

NCT04049383 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: PRO00045861
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This phase 1 study will evaluate the safety and efficacy of a CAR-T cell therapy directed against two B cell antigens (CD19 CD20) and produced under good manufacturing practice (GMP) conditions using the closed system CliniMACS Prodigy device in B ALL.

Conditions

Acute Lymphoblastic Leukemia With Failed Remission; Acute Lymphoblastic Leukemia Recurrent; Acute Lymphoblastic Leukemia, in Relapse; Acute Lymphoblastic Leukemia Not Having Achieved Remission; Acute Lymphoblastic Leukemia, Pediatric; Acute Lymphoblastic Leukemia

Keywords

Acute Lymphoblastic Leukemia; B-cell; CAR-T

Outcome Measures

Primary Outcomes (1)

• Number of Adverse Events after CAR 20/19-T Cell Infusion.

  Adverse events will be measured and recorded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Occurrence of adverse events, defined as either CRS related Grade 3/4 toxicity or other NCI CTCAE version 5 non-hematologic ≥ grade 3 signs/symptoms, laboratory toxicities and clinical events that are possibly, probably or definitely related to study treatment at any time from the infusion until day +28 post CAR-T infusion.

  28 days after infusion

Study Arms (4)

5 x 10^5 CAR-20/19-T cells/kg

EXPERIMENTAL

The study will utilize a 3+3 dose escalation design in ALL followed by a six-patient expansion cohort.

Biological: CAR-20/19-T cells (5 x 10^5 CAR-20/19-T cells/kg)

1 x10^6 CAR-20/19-T cells/kg

EXPERIMENTAL

The study will utilize a 3+3 dose escalation design in ALL followed by a six-patient expansion cohort.

Biological: CAR-20/19-T cells (1 x10^6 CAR-20/19-T cells/kg)

2.5 x10^6 CAR-20/19-T cells/kg

EXPERIMENTAL

The study will utilize a 3+3 dose escalation design in ALL followed by a six-patient expansion cohort.

Biological: CAR-20/19-T cells (2.5 x10^6 CAR-20/19-T cells/kg)

Dose Expansion Phase

EXPERIMENTAL

The study will utilize a 3+3 dose escalation design in ALL followed by a six-patient expansion cohort. Subjects will receive one of three dose levels. The dose expansion arm will be updated with the appropriate dose in the future based on the escalation results.

Biological: CAR-20/19-T cells (5 x 10^5 CAR-20/19-T cells/kg); Biological: CAR-20/19-T cells (1 x10^6 CAR-20/19-T cells/kg); Biological: CAR-20/19-T cells (2.5 x10^6 CAR-20/19-T cells/kg); Biological: CAR-20/19-T cells

Interventions

CAR-20/19-T cells (5 x 10^5 CAR-20/19-T cells/kg) BIOLOGICAL

The investigational agent in this protocol is the CAR-20/19-T cells.CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection. Subjects will receive one of three dose levels of CAR-20/19-T cells based on the dose escalation design. Dose Level -1: 5 x 10\^5 CAR-20/19-T cells/kg

5 x 10^5 CAR-20/19-T cells/kg; Dose Expansion Phase

CAR-20/19-T cells BIOLOGICAL

The investigational agent in this protocol is the CAR-20/19-T cells.CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection. Subjects will receive one of three dose levels of CAR-20/19-T cells based on the dose escalation design. The dose expansion dose level is still to be determined and this section will be updated.

Dose Expansion Phase

CAR-20/19-T cells (1 x10^6 CAR-20/19-T cells/kg) BIOLOGICAL

The investigational agent in this protocol is the CAR-20/19-T cells.CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection. Subjects will receive one of three dose levels of CAR-20/19-T cells based on the dose escalation design. Dose Level 0: 1 x10\^6 CAR-20/19-T cells/kg (starting dose level)

1 x10^6 CAR-20/19-T cells/kg; Dose Expansion Phase

CAR-20/19-T cells (2.5 x10^6 CAR-20/19-T cells/kg) BIOLOGICAL

The investigational agent in this protocol is the CAR-20/19-T cells.CAR-20/19-T cells will be administered either fresh or thawed after cryopreservation by IV injection. Subjects will receive one of three dose levels of CAR-20/19-T cells based on the dose escalation design. Dose Level 1: 2.5 x10\^6 CAR-20/19-T cells/kg (goal cell dose)

2.5 x10^6 CAR-20/19-T cells/kg; Dose Expansion Phase

Eligibility Criteria

• Age: 1 Year - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of B-cell ALL: During the safety phase patients enrolled will be age ≥ 18 to age ≤ 70. Once those three patients have passed the 28-day waiting period post infusion, clearance from the FDA will be obtained to enroll pediatric patients. After FDA clearance -Patients must be aged ≥ 1 year and ≤ 70 years. All patients will have relapsed, refractory disease and no available curative options that meet clinical criteria to initiate treatment.
• Relapsed or refractory B cell ALL defined as one of the following:
• Primary refractory disease.
• Relapsed or refractory disease after two or more lines of systemic therapy.
• Relapsed or refractory disease after allogeneic transplant provided subject is at least 100 days from stem cell transplant at the time of enrollment and off of immunosuppressive medications for at least four weeks prior to enrollment.
• Measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, or cytogenetics, or morphological disease in the bone marrow.
• Subjects with B-cell ALL must have either CD19 or CD20 positive disease on their most recent bone marrow performed. A minimum of 5% CD19 or CD20 positivity on prior biopsy or bone marrow aspiration (BMA) is required.
• Subjects with Ph+ ALL are eligible if they have relapsed or refractory disease and have failed at least two tyrosine kinase inhibitors.
• Absolute cluster of differentiation 3 (CD3)+ T cell count ≥100/mm\^3.
• a. Subjects who receive chemotherapy and/or steroids after CD3+ T-cell count, but before apheresis, will require this test to be repeated.
• Lumbar puncture with CSF analysis by cytology with no evidence of disease.
• Karnofsky/Lansky performance score ≥70.
• Normal Baseline Neurological Evaluation: Mini-Mental Status Exam Score 24-30.
• Adequate hepatic function, defined as aspartate aminotransferase (AST) and alanine transaminase (ALT) \<3 x upper limit of normal (ULN); serum bilirubin and alkaline phosphatase \<2 x ULN, or considered not clinically significant as per the clinical PIs discretion (e.g. Gilbert's or indirect hyperbilirubinemia) or felt to be due to underlying disease.
• Adequate renal function defined as creatinine clearance or radioisotope glomerular filtration rate (GFR) \> 70 ml/min/1.73 M2

You may not qualify if:

• Positive beta-human chorionic gonadotropin (HCG) in female of childbearing potential.
• Subjects with known systemic allergy to bovine or murine products.
• Confirmed active human immunodeficiency virus (HIV), Hepatitis B or C infection. 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.
• History of significant autoimmune disease OR active, uncontrolled autoimmune phenomenon: such as systemic lupus erythematous, Wegner's glomerulonephritis, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura (AIHA, ITP) requiring steroid therapy defined as \>20 mg of prednisone.
• Presence of ≥ grade 3 non-hematologic toxicities as per CTCAE version 5 from any previous treatment unless it is felt to be due to underlying disease.
• Concurrent use of investigational therapeutic agents or enrollment on another therapeutic clinical trial at any institution.
• Refusal to participate in the long-term follow-up protocol.
• Central nervous system (CNS) Abnormalities:
• Subjects with prior CNS disease that has been effectively treated will be eligible providing treatment was \> four weeks before enrollment and a remission documented within four weeks of planned CAR-T cell infusion. Subjects will be excluded if they have any signs of neurotoxicity at baseline or evidence of chloroma or leukemic infiltrates on MRI.
• Presence of CNS-3 disease defined as detectable cerebrospinal blast cells in a sample of CSF with ≥ 5 white blood cells (WBCs) per mm\^3 with or without neurological changes, and presence of CNS-2 disease defined as detectable cerebrospinal blast cells in a sample of CSF with \< 5 WBCs per mm\^3 with neurological changes will be excluded.
• Note: Subjects with CNS-1 (no detectable leukemia in the CSF) and those with CNS-2 without clinically evident neurological changes are eligible to participate in the study. History or presence of any CNS disorder, such as a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, any autoimmune disease with CNS involvement, posterior reversible encephalopathy syndrome (PRES), or cerebral edema are excluded.
• Previous recipients of allogeneic hematopoietic stem cell transplantation (AHCT) are excluded if they are \<100 days' post-transplant, have evidence of active graft-versus-host-disease (GVHD) of any grade, or are currently on immunosuppression.
• Anti-CD20 antibody treatment within four weeks of cell infusion.
• Anti-CD19 antibody treatment within four weeks of cell infusion.
• Cytotoxic chemotherapy other than lymphodepletion within 14 days of CAR-T cell infusion.

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• Children's Hospital and Health System Foundation, Wisconsin: collaborator

Study Sites (1)

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

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

Study Officials

• Julie-An Talano, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: There will be two phases of this study. A dose escalation phase to determine the safe CAR-20/19-T cell dose in patients B-cell ALL. Once the desired dose has been identified there will be a six-patient dose expansion phase at the specified dose level.

Study Record Dates

• First Submitted: August 6, 2019
• First Posted: August 8, 2019
• Study Start: October 16, 2020
• Primary Completion: June 1, 2025
• Study Completion: September 1, 2025
• Last Updated: January 12, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)