CAR20.19.22 T-cells in Relapsed, Refractory B-cell Malignancies

NCT05094206 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: PRO00041528
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

In this phase I study, the investigators will first evaluate the safety of CAR20.19.22 T-cells in patients with B-cell non-Hodgkin lymphoma (NHL) / chronic lymphocytic leukemia (CLL).

Conditions

B-cell Non Hodgkin Lymphoma; B-cell Chronic Lymphocytic Leukemia

Keywords

B-cell antigens; B-cell Non Hodgkin Lymphoma; B-cell Chronic Lymphocytic Leukemia; CAR-T; Chimeric antigen receptor T-cell therapy; CAR Therapy

Outcome Measures

Primary Outcomes (3)

• Number of Non-hematologic Adverse Events after Infusion

  Occurrence of adverse events will be defined as non-hematologic Grade 3/4 toxicity grade per NCI CTCAE version 5.0.

  28 days after infusion

• Number of grade 3-4 cytokine release syndrome (CRS).

  Grade 3-4 CRS as graded per the recent Transplant and Cell Therapy (TCT) consensus criteria.

  28 days after infusion

• Number of grade 3-4 immune effector cell-associated neurotoxicity syndrome (ICANS)

  Grade 3-4 ICANS as graded per the recent Transplant and Cell Therapy (TCT) consensus criteria.

  28 days after infusion

Study Arms (10)

Indolent B-cell NHL Dose Level -2: 0.75x10^6 cells/kg: CAR20.19.22

EXPERIMENTAL

The investigators will start at a dose of 2.5x10\^6 cells/kg and either escalate or de-escalate based on the presence of toxicities.

Biological: 0.75x10^6 cells/kg CAR20.19.22 cells

Indolent B-cell NHL Dose Level -1: 1x10^6 cells/kg: CAR20.19.22

EXPERIMENTAL

The investigators will start at a dose of 2.5x10\^6 cells/kg and either escalate or de-escalate based on the presence of toxicities.

Biological: 1x10^6 cells/kg CAR20.19.22 cells

Indolent B-cell NHL Dose Level 0: 2.5x10^6 cells/kg: CAR20.19.22

EXPERIMENTAL

The investigators will start at a dose of 2.5x10\^6 cells/kg and either escalate or de-escalate based on the presence of toxicities.

Biological: 2.5x10^6 cells/kg CAR20.19.22 cells

Indolent B-cell NHL Dose Level 1: 5x10^6 cells/kg: CAR20.19.22

EXPERIMENTAL

The investigators will start at a dose of 2.5x10\^6 cells/kg and either escalate or de-escalate based on the presence of toxicities.

Biological: 5x10^6 cells/kg CAR20.19.22 cells

Indolent B-cell NHL Dose Expansion: CAR20.19.22

EXPERIMENTAL

The maximum tolerated dose intervention will be updated when it is determined. It will be one of four doses: 0.75x10\^6 cells/kg, 1x10\^6 cells/kg, 2.5x10\^6 cells/kg or 5x10\^6 cells/kg.

Biological: Dose expansion: The maximum tolerated dose of CAR20.19.22 cells

Aggressive B-cell NHL Dose Level -1: .75x10^6 cells/kg: CAR20.19.22

EXPERIMENTAL

The investigators will start at a dose of 1x10\^6 cells/kg and either escalate or de-escalate based on the presence of toxicities.

Biological: 0.75x10^6 cells/kg CAR20.19.22 cells

Aggressive B-cell NHL Dose Level 0: 1x10^6 cells/kg: CAR20.19.22

EXPERIMENTAL

The investigators will start at a dose of 1x10\^6 cells/kg and either escalate or de-escalate based on the presence of toxicities.

Biological: 1x10^6 cells/kg CAR20.19.22 cells

Aggressive B-cell NHL Dose Level 1: 2.5x10^6 cells/kg: CAR20.19.22

EXPERIMENTAL

The investigators will start at a dose of 1x10\^6 cells/kg and either escalate or de-escalate based on the presence of toxicities.

Biological: 2.5x10^6 cells/kg CAR20.19.22 cells

Aggressive B-cell NHL Dose Level 2: 5x10^6 cells/kg: CAR20.19.22

EXPERIMENTAL

The investigators will start at a dose of 1.0x10\^6 cells/kg and either escalate or de-escalate based on the presence of toxicities.

Biological: 5x10^6 cells/kg CAR20.19.22 cells

Aggressive B-cell NHL Dose Expansion: CAR20.19.22

EXPERIMENTAL

The maximum tolerated dose intervention will be updated when it is determined. It will be one of four doses: 0.75x10\^6 cells/kg, 1x10\^6 cells/kg, 2.5x10\^6 cells/kg or 5x10\^6 cells/kg.

Biological: Dose expansion: The maximum tolerated dose of CAR20.19.22 cells

Interventions

0.75x10^6 cells/kg CAR20.19.22 cells BIOLOGICAL

Dose escalation: CAR20.19.22 cells will be administered at one of three dose levels either fresh or thawed after cryopreservation by IV injection. Dose expansion: The maximum tolerated dose intervention will be updated when it is determined. It will be one of four doses: 0.75x10\^6 cells/kg, 1x10\^6 cells/kg, 2.5x10\^6 cells/kg or 5x10\^6.

Aggressive B-cell NHL Dose Level -1: .75x10^6 cells/kg: CAR20.19.22; Indolent B-cell NHL Dose Level -2: 0.75x10^6 cells/kg: CAR20.19.22

1x10^6 cells/kg CAR20.19.22 cells BIOLOGICAL

CAR20.19.22 cells will be administered at one of four dose levels either fresh or thawed after cryopreservation by IV injection. Dose expansion: The maximum tolerated dose intervention will be updated when it is determined. It will be one of four doses: 0.75x10\^6 cells/kg, 1x10\^6 cells/kg, 2.5x10\^6 cells/kg or 5x10\^6.

Aggressive B-cell NHL Dose Level 0: 1x10^6 cells/kg: CAR20.19.22; Indolent B-cell NHL Dose Level -1: 1x10^6 cells/kg: CAR20.19.22

2.5x10^6 cells/kg CAR20.19.22 cells BIOLOGICAL

CAR20.19.22 cells will be administered at one of four dose levels either fresh or thawed after cryopreservation by IV injection. The maximum tolerated dose intervention will be updated when it is determined. It will be one of four doses: 0.75x10\^6 cells/kg, 1x10\^6 cells/kg, 2.5x10\^6 cells/kg or 5x10\^6.

Aggressive B-cell NHL Dose Level 1: 2.5x10^6 cells/kg: CAR20.19.22; Indolent B-cell NHL Dose Level 0: 2.5x10^6 cells/kg: CAR20.19.22

5x10^6 cells/kg CAR20.19.22 cells BIOLOGICAL

CAR20.19.22 cells will be administered at one of four dose levels either fresh or thawed after cryopreservation by IV injection. The maximum tolerated dose intervention will be updated when it is determined. It will be one of four doses: 0.75x10\^6 cells/kg, 1x10\^6 cells/kg, 2.5x10\^6 cells/kg or 5x10\^6.

Aggressive B-cell NHL Dose Level 2: 5x10^6 cells/kg: CAR20.19.22; Indolent B-cell NHL Dose Level 1: 5x10^6 cells/kg: CAR20.19.22

Dose expansion: The maximum tolerated dose of CAR20.19.22 cells BIOLOGICAL

Dose expansion: The maximum tolerated dose intervention will be updated when it is determined. It will be one of four doses: 0.75x10\^6 cells/kg, 1x10\^6 cells/kg, 2.5x10\^6 cells/kg or 5x10\^6 cells/kg.

Aggressive B-cell NHL Dose Expansion: CAR20.19.22; Indolent B-cell NHL Dose Expansion: CAR20.19.22

Eligibility Criteria

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

You may qualify if:

• Patients must be aged ≥18 years to 80 years with relapsed or refractory B-cell non-Hodgkin Lymphoma or chronic lymphocytic leukemia.
• Absolute CD3 count ≥50 mm\^3.
• MRI brain and lumbar puncture with cerebrospinal fluid (CSF) analysis by cytology and flow cytometry without evidence of central nervous system (CNS) involvement ONLY in patients with history of CNS involvement or clinical suspicion at the time of enrollment.
• Measurable disease must be documented within 4 weeks of apheresis date and is defined as nodal lesions \>15 mm in the long axis or extranodal lesions \>10 mm in long OR bone marrow involvement that is biopsy proven.
• Karnofsky performance score ≥70.
• Adequate hepatic function, defined as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase \< 3x upper limit of normal (ULN); serum bilirubin \< 2.0 mg/dL
• ANC≥1000 with no G-CSF within 72 hours or pegylated G-CSF within 10 days unless bone marrow involvement is present.
• Platelets ≥ 50,000 with no transfusion within 72 hours of eligibility testing unless bone marrow involvement is present.
• Adequate renal function, defined as creatinine clearance≥60 ml/min AND serum Cr≤1.5 mg/dL.
• Able to provide written informed consent.
• Agree to practice birth control during the study.
• Adequate cardiac function as indicated by New York Heart Association (NYHA) classification I or II AND left ventricular ejection fraction of ≥45% (by cardiac echocardiogram (ECHO) or MUGA) and adequate pulmonary function as indicated by room air oxygen saturation of ≥90%.
• Expected survival \>12 weeks.
• Negative urine or serum pregnancy test in females of childbearing potential at study entry.
• Meet criteria for regarding fertility and contraception detailed below.

You may not qualify if:

• Positive beta-human chorionic gonadotropin (HCG) in female of child-bearing potential.
• Confirmed active human immunodeficiency virus (HIV), Hepatitis B or C infection.
• History of significant autoimmune disease OR active, uncontrolled autoimmune phenomenon requiring steroid therapy defined as \>20 mg of prednisone or equivalent daily.
• Presence of ≥grade 3 non-hematologic toxicities as per CTCAE version 5.0 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. Minimum of 14 days or 5 half-lives of the drug (whichever is shorter) washout prior to apheresis.
• Refusal to participate in the long-term follow-up protocol.
• Patients with active CNS involvement by malignancy on MRI or by lumbar puncture.
• a. Patients with prior CNS disease that has been effectively treated will be eligible providing treatment was \>4 weeks before enrollment and a remission documented within 8 weeks of planned CAR T-cell infusion by MRI brain and CSF analysis.
• 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 directed treatment within 4 weeks of cell infusion.
• Anti-CD19 directed treatment within 4 weeks of cell infusion.
• Anti-CD22 directed treatment within 4 weeks of cell infusion.
• Cytotoxic chemotherapy, oral chemotherapeutic agents or antibody directed treatment within 14 days of lymphodepletion.
• Radiation is allowed to a single symptomatic site as long as other sites of measurable disease are present on eligibility scan.
• If patients receive steroids or any systemic disease targeting treatment, repeat scans are needed to confirm disease burden pre-lymphodepletion.

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• Miltenyi Biotec, Inc.: collaborator

Study Sites (1)

Medical College of Wisconsin and Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Nirav Shah, 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: Associate Professor

Study Record Dates

• First Submitted: October 17, 2021
• First Posted: October 26, 2021
• Study Start: June 30, 2022
• Primary Completion: January 29, 2024
• Study Completion: January 29, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)