A Study of CC-97540, CD19-targeted NEX-T Chimeric Antigen Receptor (CAR) T Cells, in Subjects With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

NCT04231747 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: CC-97540-NHL-001U1111-1244-9049
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 14

Brief Summary

This is a Phase 1, first-in-human, open-label, multicenter study of CC-97540, CD19-targeted NEX-T chimeric antigen receptor (CAR) T cells, in subjects with relapsed or refractory B-cell non-Hodgkin lymphoma. The study will consist of 2 parts: dose-escalation (Part A) and dose-expansion (Part B). The dose-escalation part (Part A) of the study is to evaluate the safety and tolerability of increasing dose levels of CC-97540 to establish a recommended Phase 2 dose (RP2D); and the dose-expansion part (Part B) of the study is to further evaluate the safety, pharmacokinetics/pharmacodynamics, and efficacy of CC-97540 at the RP2D.

Conditions

Lymphoma Non-Hodgkin; Agressive Lymphoma; Diffuse-large B-cell Lymphoma (DLBCL)

Keywords

Lymphoma; B-cell non-Hodgkin lymphoma; Agressive Lymphoma; Diffuse-large B-cell Lymphoma; DLBCL; NHL; CC-97540; CD19; NEX-T chimeric antigen receptor (CAR) T cells; CAR-T; CART

Outcome Measures

Primary Outcomes (1)

• Adverse Events (AEs)

  An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.ject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the sub

  From the time of informed consent and follow up to 2 years after infusion of CC-97540

Secondary Outcomes (11)

• Complete Response Rate (CRR)

  Up to 2 years after CC-97540 infusion

• Overall response Rate (ORR)

  Up to 2 years after CC-97540 infusion

• Duration of response (DOR)

  Up to 2 years after CC-97540 infusion

• Time to response (TTR)

  Up to 2 years after CC-97540 infusion

• Time to complete response (TTCR)

  Up to 2 years after CC-97540 infusion

Study Arms (1)

CC-97540 monotherapy

EXPERIMENTAL

Subjects will be assigned to receive CC-97540 followed by 3 consecutive doses of lymphodepleting chemotherapy (fludarabine IV (30 mg/m2/day) and cyclophosphamide IV (300 mg/m2/day).

Biological: CC-97540

Interventions

CC-97540 BIOLOGICAL

Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) to produce CC 97540. During CC 97540 production, subjects may receive bridging chemotherapy for disease control. Upon successful generation of CC 97540 product, subjects will receive treatment with CC 97540 therapy. Each cycle will include lymphodepleting chemotherapy followed by one dose of CC 97540 administered by intravenous (IV) injection.

CC-97540 monotherapy

Eligibility Criteria

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

You may qualify if:

• Subjects must satisfy the following criteria to be enrolled in the study:
• Age ≥ 18 years at the time of informed consent.
• Signed written informed consent obtained prior to any study procedure.
• Willing and able to adhere to the study visit schedule and other protocol requirements.
• Relapsed and/or refractory aggressive B-cell NHL as defined:
• Histologically confirmed DLBCL not otherwise specified, high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (HGBCL), transformed DLBCL from follicular (tFL) or marginal zone lymphoma (tMZL), primary mediastinal B-cell lymphoma (PMBCL), or FL grade 3b (FL3B) (Note: Subjects with Richter's transformation (transformed DLBCL from CLL) are ineligible) AND
• Have relapsed and/or refractory disease after at least 2 lines of systemic therapy which must include at least one anthracycline and rituximab (or other anti-CD20 monoclonal antibody).
• Note: Lines of therapy will exclude those given for prior indolent lymphoma. It is not required for subjects to have had anthracycline for their DLBCL if received for indolent disease AND/OR
• Have relapsed and/or refractory DLBCL failed to ASCT treatment. Note: ASCT failure is defined as either failure to achieve an objective response (PR or better), or disease progression after ASCT(Note: Subjects who were not candidates to receive ASCT treatment (due to age or other factors) are eligible; the reason for not receiving ASCT must be documented in the electronic case report form (eCRF).
• Positron emission tomography (PET)-positive disease as per the Lugano Classification (at screening or following bridging therapy, whichever is later).
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function as detailed in the protocol.
• Adequate vascular access for leukapheresis.
• Willing and able to undergo tumor biopsies (in subjects with accessible disease).
• Agree to not donate blood, organs, sperm or semen, and egg cells for usage in other individuals as detailed in the protocol.

You may not qualify if:

• The presence of any of the following will exclude a subject from enrollment:
• Uncontrolled medical, psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol, as judged by the Investigator; or unwillingness or inability to follow the procedures required in the protocol.
• Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
• Any condition that confounds the ability to interpret data from the study.
• Central nervous system (CNS)-only involvement by malignancy (note: subjects with pathologically-confirmed secondary CNS involvement are allowed).)
• Prior CAR T- cell or genetically-modified T- cell therapy, or prior CD19- targeted therapy (including, but not limited to, anti-CD19 mAbs or bispecific antibodies).)
• Treatment with the following therapies or procedure within the specified period:
• Therapeutic doses of corticosteroids (defined as \> 20 mg/day prednisone or equivalent) within 14 days before leukapheresis administration. Physiologic replacement, topical, and inhaled steroids are permitted.
• Cytotoxic chemotherapeutic agents (eg, doxorubicin, vincristine, gemcitabine, oxaliplatin, carboplatin, etoposide) within 7 days of leukapheresis, with the exception of alkylating agents.
• Intrathecal therapy (eg, dexamethasone, methotrexate, cytosine arabinoside, cytarabine) within 7 days of leukapheresis.
• Oral chemotherapeutic agents, including lenalidomide and ibrutinib, are allowed if at least 5 half-lives have elapsed prior to leukapheresis.
• Alkylating agents (eg, cyclophosphamide, ifosfamide, bendamustine) within 4 weeks of leukapheresis.
• Any experimental therapy within 8 weeks (for biologics) or 5 half-lives (for small molecules) before leukapheresis
• Immunosuppressive therapies within 4 weeks of leukapheresis (eg, calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolate, rapamycin, immunosuppressive antibodies such as anti-TNF, anti-IL6, or anti-IL6R)
• Monoclonal antibodies (including rituximab, polatuzumab, etc.) within 7 days.

Sponsors & Collaborators

• Juno Therapeutics, a Subsidiary of Celgene: lead

Study Sites (14)

Local Institution - 003

Birmingham, Alabama, 35294-3300, United States

Location

Local Institution - 004

Atlanta, Georgia, 30342, United States

Location

Local Institution - 011

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Nebraska Medicine Fred and Pamela Buffett Cancer Center

Omaha, Nebraska, 68105, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Local Institution - 001

New York, New York, 10021, United States

Location

Local Institution - 008

New York, New York, 10065, United States

Location

Local Institution - 010

Charlotte, North Carolina, 28204, United States

Location

Oregon Health and Science University OHSU

Portland, Oregon, 97239, United States

Location

Huntsman Cancer Institute - University of Utah

Salt Lake City, Utah, 84112, United States

Location

Foothills Medical Centre - Tom Baker Cancer Centre

Calgary, Alberta, T2N 2T9, Canada

Location

Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Juravinski Cancer Centre

Hamilton, Ontario, L8V 1C3, Canada

Location

Related Publications (1)

• Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

  PMID: 34515338 DERIVED

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Dendritic Cell Sarcoma, Interdigitating; Lymphoma; Lymphoma, B-Cell

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Histiocytic Disorders, Malignant; Histiocytosis

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: January 14, 2020
• First Posted: January 18, 2020
• Study Start: May 21, 2020
• Primary Completion: February 1, 2024
• Study Completion: February 1, 2024
• Last Updated: May 20, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: See Plan Description
• Access Criteria: See Plan Description

Locations

US (11); CA (3)