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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04231747
Recruitment Status : Recruiting
First Posted : January 18, 2020
Last Update Posted : June 30, 2020
Sponsor:
Information provided by (Responsible Party):
Juno Therapeutics, a Subsidiary of Celgene

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.


Condition or disease Intervention/treatment Phase
Lymphoma Non-Hodgkin Agressive Lymphoma Diffuse-large B-cell Lymphoma (DLBCL) Biological: CC-97540 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : May 22, 2020
Estimated Primary Completion Date : January 31, 2025
Estimated Study Completion Date : January 31, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: CC-97540 monotherapy
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

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.





Primary Outcome Measures :
  1. Adverse Events (AEs) [ Time Frame: From the time of informed consent and follow up to 2 years after infusion of CC-97540 ]
    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


Secondary Outcome Measures :
  1. Complete Response Rate (CRR) [ Time Frame: Up to 2 years after CC-97540 infusion ]
    The proportion of subjects with a best overall response of complete response (CR).

  2. Overall response Rate (ORR) [ Time Frame: Up to 2 years after CC-97540 infusion ]
    The proportion of subjects achieving CR or partial response (PR).

  3. Duration of response (DOR) [ Time Frame: Up to 2 years after CC-97540 infusion ]
    The time from first response to progressive disease (PD) or death.

  4. Time to response (TTR) [ Time Frame: Up to 2 years after CC-97540 infusion ]
    Time from CC-97540 infusion to the first documentation of response (CR or PR).

  5. Time to complete response (TTCR) [ Time Frame: Up to 2 years after CC-97540 infusion ]
    Time from CC-97540 infusion to the first documentation of CR

  6. Progression free survival (PFS) [ Time Frame: Up to 2 years after CC-97540 infusion ]
    Time from CC-97540 infusion to the first documentation of PD, or death from any cause, whichever occurs first

  7. Overall survival (OS) [ Time Frame: Up to 2 years after CC-97540 infusion ]
    Time from CC-97540 infusion to death

  8. Pharmacokinetics - peak expansion (Cmax) [ Time Frame: Up to 2 years after CC-97540 infusion ]
    Maximum blood concentration

  9. Pharmacokinetics -time to peak expansion (tmax) [ Time Frame: Up to 2 years after CC-97540 infusion ]
    Time to peak (maximum) blood concentration

  10. Pharmacokinetics - elimination half-life (t1/2) [ Time Frame: Up to 2 years after CC-97540 infusion ]
    Elimination half-life

  11. Pharmacokinetics - Area under curve (AUC) [ Time Frame: Up to 2 years after CC-97540 infusion ]
    Area under the curve



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Subjects must satisfy the following criteria to be enrolled in the study:

  1. Age ≥ 18 years at the time of informed consent.
  2. Signed written informed consent obtained prior to any study procedure.
  3. Willing and able to adhere to the study visit schedule and other protocol requirements.
  4. Relapsed and/or refractory aggressive B-cell NHL as defined:

    1. 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) AND
    2. 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

    3. 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.
  5. Positron emission tomography (PET)-positive disease as per the Lugano Classification.
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  7. Adequate organ function as detailed in the protocol.
  8. Adequate vascular access for leukapheresis.
  9. Willing and able to undergo tumor biopsies (in subjects with accessible disease).
  10. Agree to not donate blood, organs, sperm or semen, and egg cells for usage in other individuals as detailed in the protocol.
  11. 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:

  1. 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.
  2. Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
  3. Any condition that confounds the ability to interpret data from the study.
  4. Central nervous system (CNS)-only involvement by malignancy (note: subjects with pathologically-confirmed secondary CNS involvement are allowed).)
  5. 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).)
  6. Treatment with the following therapies or procedure within the specified period:

    1. 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.
    2. Cytotoxic chemotherapeutic agents (eg, doxorubicin, vincristine, gemcitabine, oxaliplatin, carboplatin, etoposide) that are not considered lymphotoxic and intrathecal therapy (IT) (see below) 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.
    3. Lymphotoxic chemotherapeutic agents (eg, cyclophosphamide, ifosfamide, bendamustine) within 4 weeks of leukapheresis.
    4. Any experimental therapy within 8 weeks (for biologics) or 5 half-lives (for small molecules) before leukapheresis
    5. 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)
    6. Donor lymphocyte infusions within 6 weeks of leukapheresis
    7. 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.
    8. Autologous stem-cell transplant (SCT) (ie, Day 0 receipt of hematopoietic stem cells) within 3 months of leukapheresis
    9. Washout of prior therapy (eg, bridging therapy for disease control)
  7. Active autoimmune disease requiring immunosuppressive therapy.
  8. 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).)
  9. Hypersensitivity to fludarabine and/or cyclophosphamide.
  10. 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:

    1. Basal or squamous cell carcinoma of the skin
    2. Carcinoma in situ of the cervix or the breast
    3. Incidental histologic finding of prostate cancer (T1a or T1b using the TNM (tumor, nodes, metastasis) clinical staging system) or prostate cancer that is curative
    4. Other completely resected stage 1 solid tumor with low risk for recurrence
  11. Active hepatitis B, hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening.
  12. Uncontrolled or active systemic fungal, bacterial, viral or other infection despite appropriate anti-infection treatment at the time of leukapheresis or pre-treatment evaluation.
  13. 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.
  14. 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.
  15. History of ≥ Grade 2 hemorrhage within 30 days of screening.
  16. Pregnant or nursing (lactating) women.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04231747


Contacts
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Contact: Associate Director Clinical Trial Disclosure 1-888-260-1599 clinicaltrialdisclosure@celgene.com

Locations
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United States, Georgia
Northside Hospital - Blood and Bone Marrow Transplant Group of Georgia Recruiting
Atlanta, Georgia, United States, 30342
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Sponsors and Collaborators
Juno Therapeutics, a Subsidiary of Celgene
Investigators
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Study Director: Ashley Koegel, MD Celgene
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Responsible Party: Juno Therapeutics, a Subsidiary of Celgene
ClinicalTrials.gov Identifier: NCT04231747    
Other Study ID Numbers: CC-97540-NHL-001
U1111-1244-9049 ( Registry Identifier: UTN )
First Posted: January 18, 2020    Key Record Dates
Last Update Posted: June 30, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

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/

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: See Plan Description
Access Criteria: See Plan Description
URL: https://www.celgene.com/research-development/clinical-trials/clinical-trials-data-sharing/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Juno Therapeutics, a Subsidiary of Celgene:
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
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases