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

Completed · Phase 1

Conditions studied: Lymphoma Non-Hodgkin, Agressive Lymphoma, Diffuse-large B-cell Lymphoma (DLBCL)

In brief

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.

Key facts

Study ID

NCT04231747

Run by

Juno Therapeutics, a Subsidiary of Celgene

People needed

24

Starts

2020-05-21

Expected to finish

2024-02-01

Last updated by the study team

2024-05-20

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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.
• Female and male subjects agree to use effective contraception 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.
• Donor lymphocyte infusions within 6 weeks of leukapheresis
• Radiation within 6 weeks of leukapheresis. Subjects must have progressive disease in irradiated lesions or have additional non-irradiated, PET-positive lesions to be eligible. Radiation to a single lesion, if additional non-irradiated PET-positive lesions are present, is allowed up to 14 days prior to leukapheresis.
• Autologous stem-cell transplant (SCT) (ie, Day 0 receipt of hematopoietic stem cells) within 3 months of leukapheresis
• Washout of prior therapy (eg, bridging therapy for disease control)
• Active autoimmune disease requiring immunosuppressive therapy.
• Allogenic SCT (ie, Day 0 receipt of hematopoietic stem cells) within 6 months of leukapheresis or presence of ongoing symptoms or treatment for chronic graft-versus host disease (GVHD).)
• Hypersensitivity to fludarabine and/or cyclophosphamide.
• Prior history of malignancies, other than studied NHL, unless the subject has been free of the disease for ≥ 2 years except for the following non-invasive malignancies:
• Basal or squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix or the breast

Where it is running

• Local Institution - 003 — Birmingham, Alabama, United States
• Local Institution - 004 — Atlanta, Georgia, United States
• Local Institution - 011 — Boston, Massachusetts, United States
• Beth Israel Deaconess Medical Center — Boston, Massachusetts, United States
• Nebraska Medicine Fred and Pamela Buffett Cancer Center — Omaha, Nebraska, United States
• Hackensack University Medical Center — Hackensack, New Jersey, United States
• Local Institution - 001 — New York, New York, United States
• Local Institution - 008 — New York, New York, United States
• Local Institution - 010 — Charlotte, North Carolina, United States
• Oregon Health and Science University OHSU — Portland, Oregon, United States
• Huntsman Cancer Institute - University of Utah — Salt Lake City, Utah, United States
• Foothills Medical Centre - Tom Baker Cancer Centre — Calgary, Alberta, Canada
• Vancouver General Hospital — Vancouver, British Columbia, Canada
• Juravinski Cancer Centre — Hamilton, Ontario, Canada

Full record on ClinicalTrials.gov

Trial information comes from ClinicalTrials.gov and is refreshed daily. TrialsForMe does not provide medical care and does not run the studies it lists.