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Lymphoma Non-HodgkinPhase 1NCT04231747

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

A Phase 1 study testing CC-97540 in people with Lymphoma Non-Hodgkin and Agressive Lymphoma, run by Juno Therapeutics, a Subsidiary of Celgene at 14 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
CC-97540
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
14 sitesin 2 countries
Study dates
21 May 2020to 1 Feb 2024
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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).)
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  • 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 locations and contacts

14 sites in 2 countries.

14 sites in 2 countries

United States11 sites

  • Local Institution - 004

    Atlanta, Georgia, 30342

  • Local Institution - 003

    Birmingham, Alabama, 35294-3300

  • Local Institution - 011

    Boston, Massachusetts, 02114

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Local Institution - 010

    Charlotte, North Carolina, 28204

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Local Institution - 001

    New York, New York, 10021

  • Local Institution - 008

    New York, New York, 10065

  • Nebraska Medicine Fred and Pamela Buffett Cancer Center

    Omaha, Nebraska, 68105

  • Oregon Health and Science University OHSU

    Portland, Oregon, 97239

  • Huntsman Cancer Institute - University of Utah

    Salt Lake City, Utah, 84112

Other trials in United States

Canada3 sites

  • Foothills Medical Centre - Tom Baker Cancer Centre

    Calgary, Alberta, T2N 2T9

  • Juravinski Cancer Centre

    Hamilton, Ontario, L8V 1C3

  • Vancouver General Hospital

    Vancouver, British Columbia, V5Z 1M9

Other trials in Canada

About this study

Official title: A Phase 1, Multicenter, Open-label 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

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.

Being tested
CC-97540
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
Medical subject headings
Lymphoma, Non-Hodgkin, Dendritic Cell Sarcoma, Interdigitating, Lymphoma, Lymphoma, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CC-97540Biological

    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.

Study groups in NCT04231747
Study groupRoleWhat they receive
CC-97540 monotherapyExperimentalSubjects 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).
Receives: Biological: CC-97540

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

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

Secondary outcomes (11)

  1. Complete Response Rate (CRR)

    The proportion of subjects with a best overall response of complete response (CR).

    Measured: Up to 2 years after CC-97540 infusion

  2. Overall response Rate (ORR)

    The proportion of subjects achieving CR or partial response (PR).

    Measured: Up to 2 years after CC-97540 infusion

  3. Duration of response (DOR)

    The time from first response to progressive disease (PD) or death.

    Measured: Up to 2 years after CC-97540 infusion

  4. Time to response (TTR)

    Time from CC-97540 infusion to the first documentation of response (CR or PR).

    Measured: Up to 2 years after CC-97540 infusion

  5. Time to complete response (TTCR)

    Time from CC-97540 infusion to the first documentation of CR

    Measured: Up to 2 years after CC-97540 infusion

  6. Progression free survival (PFS)

    Time from CC-97540 infusion to the first documentation of PD, or death from any cause, whichever occurs first

    Measured: Up to 2 years after CC-97540 infusion

  7. Overall survival (OS)

    Time from CC-97540 infusion to death

    Measured: Up to 2 years after CC-97540 infusion

  8. Pharmacokinetics - peak expansion (Cmax)

    Maximum blood concentration

    Measured: Up to 2 years after CC-97540 infusion

  9. Pharmacokinetics -time to peak expansion (tmax)

    Time to peak (maximum) blood concentration

    Measured: Up to 2 years after CC-97540 infusion

  10. Pharmacokinetics - elimination half-life (t1/2)

    Elimination half-life

    Measured: Up to 2 years after CC-97540 infusion

  11. Pharmacokinetics - Area under curve (AUC)

    Area under the curve

    Measured: Up to 2 years after CC-97540 infusion

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 Jan 2020
  2. Study start21 May 2020
  3. Primary completion1 Feb 2024
  4. Study completion1 Feb 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
24 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04231747
Sponsor's protocol ID
CC-97540-NHL-001
Other IDs
U1111-1244-9049
Status last verified
May 2024
First submitted
14 Jan 2020
Last updated
20 May 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

Publications

  • 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.

    PubMed 34515338

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CC-97540 in people with Lymphoma Non-Hodgkin and Agressive Lymphoma, run by Juno Therapeutics, a Subsidiary of Celgene at 14 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 May 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Adverse Events (AEs) (time frame: From the time of informed consent and follow up to 2 years after infusion of CC-97540). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04231747, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 May 2024.

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