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

J

Juno Therapeutics

Status and phase

Completed
Phase 1

Conditions

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

Treatments

Biological: CC-97540

Study type

Interventional

Funder types

Industry

Identifiers

NCT04231747
U1111-1244-9049 (Registry Identifier)
CC-97540-NHL-001

Details and patient eligibility

About

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.

Enrollment

24 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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.

Exclusion criteria

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
  • Incidental histologic finding of prostate cancer (T1a or T1b using the TNM (tumor, nodes, metastasis) clinical staging system) or prostate cancer that is curative
  • Other completely resected stage 1 solid tumor with low risk for recurrence
  • Active hepatitis B, hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening.
  • Uncontrolled or active systemic fungal, bacterial, viral or other infection despite appropriate anti-infection treatment at the time of leukapheresis or pre-treatment evaluation.
  • History of any one of the following cardiovascular conditions within the 6 months prior to screening: Class III or IV heart failure as defined by the New York Heart Association, myocardial infarction, unstable angina, angioplasty or stenting, or other clinically significant cardiac disease.
  • History or presence of clinically significant CNS pathology such as seizure disorder, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, or cerebellar disease. Presence of clinically active psychosis.
  • History of ≥ Grade 2 hemorrhage within 30 days of screening.
  • Pregnant or nursing (lactating) women.

Previous SARS-CoV-2 infection within 10 days for mild or asymptomatic infections or 20 days for severe/critical illness prior to leukapheresis or initiation of LD chemotherapy.

-Acute symptoms must have resolved and based on investigator assessment in consultation with the Sponsor Medical Monitor, there are no sequelae that would place the subject at a higher risk of receiving study treatment.

Previous SARS-CoV-2 vaccine within 14 days prior to leukapheresis or initiation of LD chemotherapy.

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

24 participants in 1 patient group

CC-97540 monotherapy
Experimental group
Description:
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).
Treatment:
Biological: CC-97540

Trial contacts and locations

14

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Data sourced from clinicaltrials.gov

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