A Safety and Efficacy Trial of JCAR017 Combinations in Subjects With Relapsed/Refractory B-cell Malignancies

NCT03310619 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: JCAR017-BCM-002U1111-1201-2046
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 9

Brief Summary

This is a global, open-label, multi-arm, parallel multi-cohort, multi-center, Phase 1/2 study to determine the safety, tolerability, PK, efficacy and patient-reported quality of life of JCAR017 in combination with various agents. This protocol is intended to evaluate various drug combinations with JCAR017, as separate arms, over the life of the protocol, using the same objectives. Each combination will be evaluated separately (ie, the intention is not to compare between combinations) for the purposes of the objectives, trial design, and statistical analysis. The following combinations will be tested: Arm A: JCAR017 in combination with durvalumab Arm B: JCAR017 in combination with CC-122 (avadomide) Arm C: JCAR017 in combination with CC-220 (iberdomide) Arm D: JCAR017 in combination with ibrutinib Arm E: JCAR017 in combination with relatlimab and/or nivolumab Arm F: JCAR017 in combination with CC-99282 Additional arms will be added by way of amendment once combination agents have been selected. The study will consist of 2 parts: dose finding (Phase 1) and dose expansion (Phase 2). Dose expansion may occur in one or more arms.

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular

Keywords

JCAR017; B-Cell Malignancies; NHL; non-Hodgkin lymphoma; CAR T cells; chimeric antigen receptor; CC-220; Ibrutinib; relatlimab; nivolumab; CC-99282

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Dose-Limiting Toxicity (DLT)

  Participants enrolled in Phase 1 are considered evaluable for DLTs if they received an infusion of conforming JCAR017 cell product and at least one dose of the combination agent and completed the specified DLT evaluation period or if they have received an infusion of conforming JCAR017 cell product and at least one dose of the combination agent and experience a DLT during the DLT evaluation period.

  From first dose of the combination agent until 1 month (28 days) after JCAR017 infusion (pre- JCAR017 cohort) or from JCAR017 infusion until 1 month (28 days) after the first dose of combination agent (post-JCAR017 cohort)

• Complete Response Rate (CRR)

  Percentage of participants achieving a complete response (CR). CR is complete radiologic response (CRR) and complete metabolic response (CMR). CR was measured using CT and PET and assessed for the presence of index and non-index lesions, spleen size, and the absence of new lesions or diseased bone marrow. To be considered as having CRR participants had to have all of the following: * Index lesions - longest transverse diameter of nodal lesions ≤ 1.5 cm and the absence of extranodal disease. * Non-index lesions - the absence of non-index lesions. * Spleen size \<13 cm * The absence of new lesions * Normal bone marrow assessment To be considered as having CMR participants had to have all of the following: * A score of 1, 2, or 3 with or without residual mass on 5-PS for index and non-index lesions. * The absence of new lesions * No evidence of FDG-avid disease in marrow and a normal bone marrow assessment

  At 3 and 6 months post-JCAR017 infusion.

Secondary Outcomes (25)

• European Organisation for Research and Treatment of Cancer - Quality of Life C30 Questionnaire (EORTC QLQ-C30) Scores - Phase 2

  At baseline and 29 days and 57 days post JCAR017 dose

• EuroQol- 5 Dimensions of Health Visual Analogue Scale (EQ-5D VAS) Scores - Phase 2

  At baseline and 1, 29, 57, 85, 180, 270, 365, 545, and 730 days post JCAR017 dose

• Number of Participants With Adverse Events (AEs)

  Up to 3 months after the dose of JCAR017 or after the last dose of the combination agent, whichever occurred last (an average of 6.5 months up until a max of 9.5 months)

• Number of Participants With Severe Adverse Events (SAEs)

  Up to 3 months after the dose of JCAR017 or after the last dose of the combination agent, whichever occurred last (an average of 6.5 months up until a max of 9.5 months)

• Change From Baseline in White Blood Cell and Platelet Numbers

  85 days after the dose of JCAR017 for Arms A, B, D, E, and F; 57 days after the dose of JCAR017 for Arm C

Study Arms (6)

Arm A: JCAR017 in combination with Durvalumab

EXPERIMENTAL

JCAR017 will be administered at a single flat dose of 50 x 10\^6 CAR+T cells or 100 x 10\^6 CAR+T cells. The combination agent will be administered at different doses and/ or schedules

Biological: JCAR017; Drug: Durvalumab

Arm B: JCAR017 in combination with CC-122

EXPERIMENTAL

This arm will test JCAR017 in combination with the CC-122. In adult subjects with R/R aggressive B-cell NHL. JCAR017 will be administered at a dose of 100 x 10\^6 CAR+T cells. The combination agent will be administered at different doses

Biological: JCAR017; Drug: CC-122

Arm C: JCAR017 in combination with CC-220

EXPERIMENTAL

This arm will test JCAR017 in combination with CC-220. In adult subjects with R/R aggressive B-cell NHL. JCAR017 will be administered at a dose of 100 x 10\^6 CAR+T cells. The combination agent will be administered at different doses

Biological: JCAR017; Drug: CC-220

Arm D: JCAR017 in combination with Ibrutinib

EXPERIMENTAL

This arm will test JCAR017 in combination with ibrutinib. In adult subjects with R/R aggressive B-cell NHL. JCAR017 will be administered at a dose of 100 x 10\^6 CAR+T cells. The combination agent will be administered at a fixed dose of 420 mg daily

Biological: JCAR017; Drug: Ibrutinib

Arm E: JCAR017 in combination with relatlimab and/or nivolumab

EXPERIMENTAL

This arm will test JCAR017 in combination with relatlimab and/or nivolumab in adult subjects with R/R aggressive B-cell NHL. JCAR017 will be administered at a dose of 100 x 10\^6 CAR+T cells. The combination agent will be administered at different doses and/or schedules

Biological: JCAR017; Drug: Relatlimab; Drug: Nivolumab

Arm F: JCAR017 in combination with CC-99282

EXPERIMENTAL

This arm will test JCAR017 in combination with CC-99282 in adult subjects with R/R aggressive B-cell NHL. JCAR017 will be administered at a dose of 100 x 10\^6 CAR+T cells. The combination agent will be administered at different doses and/or schedules.

Biological: JCAR017; Drug: CC-99282

Interventions

JCAR017 BIOLOGICAL

Gene modified autologous T cells

Arm A: JCAR017 in combination with Durvalumab; Arm B: JCAR017 in combination with CC-122; Arm C: JCAR017 in combination with CC-220; Arm D: JCAR017 in combination with Ibrutinib; Arm E: JCAR017 in combination with relatlimab and/or nivolumab; Arm F: JCAR017 in combination with CC-99282

Durvalumab DRUG

Anti-PD-L1

Also known as: MEDI4736

Arm A: JCAR017 in combination with Durvalumab

CC-122 DRUG

Pleiotropic Pathway Modifier

Arm B: JCAR017 in combination with CC-122

Ibrutinib DRUG

Ibrutinib

Arm D: JCAR017 in combination with Ibrutinib

CC-220 DRUG

CC-220

Arm C: JCAR017 in combination with CC-220

Relatlimab DRUG

Relatlimab

Arm E: JCAR017 in combination with relatlimab and/or nivolumab

Nivolumab DRUG

Nivolumab

Arm E: JCAR017 in combination with relatlimab and/or nivolumab

CC-99282 DRUG

CC-99282

Arm F: JCAR017 in combination with CC-99282

Eligibility Criteria

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

You may qualify if:

• Subject is ≥ 18 years of age at the time of signing the informed consent form ().
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
• Subject must have aggressive B-cell NHL according to "the 2016 revision of the WHO classification of lymphoid neoplasms", histologically confirmed at last relapse by the treating institution, defined as:
• Diffuse large B-cell lymphoma (DLBCL) Not otherwise specified (NOS) including transformed indolent Non-Hodgkin lymphoma (NHL)
• Follicular lymphoma Grade 3B
• T cell/histiocyte-rich large B-cell lymphoma
• Epstein-Barr virus (EBV) positive DLBCL, NOS
• Primary mediastinal (thymic) large B-cell lymphoma
• High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (double/triple-hit lymphoma)
• Subjects disease must have relapsed or be refractory to at least 2 prior lines of therapy. Previous therapy must have included a CD20-targeted agent and an anthracycline.
• Subject must have
• Positron emission tomography (PET)-positive (Deauville score 4 or 5) and computed tomography (CT) measurable disease as per Lugano Classification
• Sum of product of perpendicular diameters (SPD) of up to 6 index lesions ≥ 25 cm2 by CT scan (not applicable to Arm A or B or subjects with Richter's transformation)
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 at screening

You may not qualify if:

• Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study based on investigator´s judgment.
• Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study based on investigator´s judgment.
• Subject has any condition that confounds the ability to interpret data from the study based on investigator´s judgment.
• Subjects with prior history of malignancies, other than aggressive R/R NHL, unless the subject has been free of the disease for ≥ 2 years with the exception of the following non-invasive malignancies:
• Basal cell carcinoma of the skin
• Squamous cell carcinoma of the skin
• Carcinoma in situ of the cervix
• Carcinoma in situ of 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
• Prior treatment with any prior gene therap y product
• Prior treatment with any adoptive T cell therapy; prior hematopoietic stem cell transplant (HSCT) is allowed
• Allogeneic HSCT within 90 days of leukapheresis
• Prior treatment with the combination agent from the assigned arm:
• Anti PD-1 or PD-L1 (Arm A and E)

Sponsors & Collaborators

• Celgene: lead

Study Sites (9)

Local Institution - 011

Duarte, California, 91010, United States

Location

Local Institution - 022

Atlanta, Georgia, 30342, United States

Location

Local Institution - 014

Chicago, Illinois, 60611-5975, United States

Location

Local Institution - 012

Boston, Massachusetts, 02114, United States

Location

Local Institution - 021

Boston, Massachusetts, 02215, United States

Location

Local Institution - 015

Omaha, Nebraska, 68198-7680, United States

Location

Local Institution - 016

Philadelphia, Pennsylvania, 19104, United States

Location

Local Institution - 020

Pittsburgh, Pennsylvania, 15232, United States

Location

Local Institution - 013

Houston, Texas, 77030, United States

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; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular

Interventions

durvalumab; 3-(5-amino-2-methyl-4-oxoquinazolin-3(4H)-yl)piperidine-2,6-dione; ibrutinib; iberdomide; relatlimab; Nivolumab

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Bristol-Myers Squibb Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Please email

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: September 25, 2017
• First Posted: October 16, 2017
• Study Start: December 20, 2017
• Primary Completion: February 15, 2023
• Study Completion: February 15, 2023
• Last Updated: April 4, 2024
• Results First Posted: April 4, 2024

Record last verified: 2024-03

Locations

US (9)