Study Evaluating the Safety and Pharmacokinetics of JCAR017 in B-cell Non-Hodgkin Lymphoma (TRANSCEND-NHL-001)

• Sponsor: Juno Therapeutics, a Subsidiary of Celgene (Industry)
• Overall Status: Recruiting
• CT.gov ID: NCT02631044
• Collaborator: (none)
• Enrollment: 314
• Locations: 15
• Arms: 2
• Anticipated Duration (Months): 83
• Patients Per Site: 20.9
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

This open-label Phase 1 study will evaluate the safety, PK, and antitumor activity of modified T cells (JCAR017) administered to adult patients with relapsed or refractory B-cell NHL. The dose and schedule of JCAR017 will be evaluated and modified, as needed, for safety and antitumor activity. We will also determine how long the modified T cells stay in the patient's body and how well JCAR017 works in treating patients with non-Hodgkin's lymphoma whose disease has come back or has not responded to treatment.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin Lymphoma; Diffuse Large B Cell Lymphoma; Follicular Lymphoma; Mantle-cell Lymphoma; Primary Mediastinal B-cell Lymphoma	Biological: JCAR017 (lisocabtagene maraleucel) single-dose schedule; Biological: JCAR017 (lisocabtagene maraleucel) 2-dose schedule	Phase 1

Detailed Description

This is an open-label, multicenter Phase 1 study to determine the safety, pharmacokinetics (PK), and antitumor activity of JCAR017 in adult patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL), primary mediastinal B-cell lymphoma (PMBCL), follicular lymphoma Grade 3B, and mantle cell lymphoma (MCL). This study will evaluate and refine the dose and schedule of JCAR017 to optimize safety and antitumor activity. A dose-confirmation group or groups will further evaluate the safety and efficacy of JCAR017 at the recommended regimen(s).

Upon successful generation of JCAR017 product, participants will receive treatment with one or more cycles of JCAR017 therapy. Each cycle will include lymphodepleting chemotherapy followed by one or two doses of JCAR017 administered by intravenous (IV) injection.

The follow-up period for each participant is approximately 24 months after the final JCAR017 infusion. Long-term follow-up for survival, toxicity, and viral vector safety will continue under a separate long-term follow-up protocol per health regulatory authority guidelines, currently up to 15 years after the last JCAR017 infusion.

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 314 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1, Multicenter, Open-Label Study of JCAR017, CD19-targeted Chimeric Antigen Receptor (CAR) T Cells, for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL)
• Actual Study Start Date: Jan 31, 2016
• Anticipated Primary Completion Date: Dec 31, 2022
• Anticipated Study Completion Date: Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: JCAR017 1-dose schedule Each cycle of JCAR017 (lisocabtagene maraleucel) will be administered as 1 intravenous (IV) injection	Biological: JCAR017 (lisocabtagene maraleucel) single-dose schedule; Participants will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JCAR017. During JCAR017 production, participants may receive low-dose chemotherapy for disease control. Upon successful generation of JCAR017 product, participants will receive treatment with JCAR017 therapy. Treatment will include lymphodepleting chemotherapy followed by one dose of JCAR017 administered by intravenous (IV) injection.
Experimental: JCAR017 2-dose schedule (no longer accruing) Each cycle of JCAR017 (lisocabtagene maraleucel) will be administered as 2 intravenous (IV) injections	Biological: JCAR017 (lisocabtagene maraleucel) 2-dose schedule; Participants will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of JCAR017. During JCAR017 production, participants may receive low-dose chemotherapy for disease control. Upon product availability, participants will receive study treatment consisting of lymphodepleting chemotherapy followed by two IV doses of JCAR017.

Outcome Measures

Primary Outcome Measures

1. Treatment-related adverse events (AEs) as assessed by CTCAE v4.03 [Up to 730 days after the final JCAR017 infusion]

   Physiological parameter

2. Dose-limiting toxicities of JCAR017 [28 days after first (single-dose schedule) or second (2-dose schedule) JCAR017 infusion]

   Physiological parameter

3. Objective response rate (ORR) [24 months]

   Lugano criteria

Secondary Outcome Measures

1. Complete response (CR) rate [24 months]

   Lugano criteria

2. Duration of response [24 months]

   Lugano criteria

3. Progression-free survival (PFS) [24 months]

   Lugano criteria

4. Overall survival [Up to 15 years]

   Physiological parameter

5. Health-related quality of life [24 months]

   Questionnaire

6. Maximum concentration of JCAR017 (Cmax) in the peripheral blood [Up to 365 days after the final JCAR017 infusion]

   qPCR

7. Time to maximum concentration of JCAR017 (Tmax) in the peripheral blood [Up to 365 days after the final JCAR017 infusion]

   qPCR

8. Area-under-the-concentration-vs-time-curve (AUC) in the peripheral blood [Up to 365 days after the final JCAR017 infusion]

   qPCR

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Age ≥18 years

2. Relapsed or refractory B-cell NHL, including

3. DLBCL cohort (no longer enrolling): DLBCL, not otherwise specified (NOS; includes transformed DLBCL from indolent histology [tDLBCL]), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (Swerdlow 2016), primary mediastinal B-cell lymphoma (PMBCL), and follicular lymphoma Grade 3B. Subjects must have been treated with an anthracycline and rituximab (or other CD20-targeted agent) and have relapsed or refractory disease after at least 2 lines of systemic therapy or after auto-HSCT.

4. MCL cohort: MCL (diagnosis must be confirmed with cyclin D1 expression or evidence of t(11;14) by cytogenetics, fluorescent in situ hybridization [FISH], or PCR) with relapsed or refractory disease after at least 2 prior lines of systemic MCL therapy. Subjects must have been treated with an alkylating agent, Bruton's tyrosine kinase inhibitor (BTKi), and rituximab (or other CD20-targeted agent).

5. PET-positive disease by Lugano classification

6. Archived tumor biopsy tissue available from the last relapse and corresponding pathology report available or, if at least one tumor-involved site is deemed accessible at time of screening, willing to undergo pre-treatment biopsy (excisional when possible) for disease confirmation. If a subject has never had a complete response, a sample from the most recent biopsy is acceptable.

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

8. Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function

9. Adequate vascular access for leukapheresis procedure

10. Participants who have received previous CD19-targeted therapy must have CD19-positive lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy.

11. Participants must agree to use appropriate contraception.

Exclusion Criteria:

1. Active central nervous system (CNS)-only involvement by malignancy (note: participants with secondary CNS involvement are allowed on study)

2. History of other primary malignancy not in remission for at least 2 years (The following are exempt from the 2-year limit: nonmelanoma skin cancer, definitively treated stage 1 solid tumor with low risk for recurrence, curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear)

3. Treatment with alemtuzumab within 6 months of leukapheresis or fludarabine or cladribine within 3 months of leukapheresis

4. Active hepatitis B, hepatitis C, or Subjects with a history of or active human immunodeficiency virus (HIV) infectionare excluded. Subjects with active hepatitis B, or active hepatitis C are also excluded. Subjects with a negative PCR assay for viral load for hepatitis B or C are permitted. Subjects positive for hepatitis B surface antigen and/or anti-hepatitis B core antibody with negative viral load are eligible and should be considered for prophylactic antiviral therapy

5. Uncontrolled systemic fungal, bacterial, viral, or other infection

6. Presence of graft-vs-host disease (GVHD)

7. History of cardiovascular disease

8. History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis

9. Pregnant or nursing women

10. Use of the following:

• Therapeutic doses of corticosteroids (defined as >20 mg/day prednisone or equivalent) within 7 days of leukapheresis or 72 hours prior to JCAR017 administration. Physiologic replacement, topical, and inhaled steroids are permitted.

• Low dose chemotherapy (e.g., vincristine, rituximab, cyclophosphamide ≤300 mg/m2) given after leukapheresis to maintain disease control must be stopped ≥7 days prior to lymphodepleting chemotherapy.

• Cytotoxic chemotherapeutic agents that are not considered lymphotoxic (see below) within 1 week of leukapheresis. Oral chemotherapeutic agents, including lenalidomide and ibrutinib, are allowed if at least 3 half-lives have elapsed prior to leukapheresis.

• Lymphotoxic chemotherapeutic agents (e.g., cyclophosphamide, ifosfamide, bendamustine) within 2 weeks of leukapheresis.

• Experimental agents within 4 weeks of leukapheresis unless no response or disease progression is documented on the experimental therapy and at least 3 half-lives have elapsed prior to leukapheresis

• Immunosuppressive therapies within 4 weeks of leukapheresis and JCAR017 administration (e.g., calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolyate, rapamycin, thalidomide, immunosuppressive antibodies such as anti-TNF, anti IL6, or anti-IL6R)

• Donor lymphocyte infusions (DLI) within 6 weeks of JCAR017 administration

• 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 2 weeks prior to leukapheresis.

• Allo-HSCT within 90 days of leukapheresis

1. Prior CAR T-cell or other genetically-modified T-cell therapy, with the exception of prior JCAR017 treatment in this protocol for subjects receiving retreatment

2. Progressive vascular tumor invasion, thrombosis, or embolism

3. Venous thrombosis or embolism not managed on a stable regimen of anticoagulation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama-Birmingham	Birmingham	Alabama	United States	35294
2	City of Hope	Duarte	California	United States	91010
3	University of California San Francisco	San Francisco	California	United States	94143
4	University of Colorado	Aurora	Colorado	United States	80045
5	Blood Marrow Transfer Group of Georgia - Northside Hospital	Atlanta	Georgia	United States	30342
6	Northwestern University	Chicago	Illinois	United States	60611
7	Local Institution - 0005	Boston	Massachusetts	United States	02114
8	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
9	Beth Israel Deaconess Medical Center	Boston	Massachusetts	United States	02215
10	University of Nebraska Medical Center	Omaha	Nebraska	United States	10065
11	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
12	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
13	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232
14	MD Anderson Cancer Center	Houston	Texas	United States	77030
15	Fred Hutchinson/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Juno Therapeutics, a Subsidiary of Celgene

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Juno Therapeutics, a Subsidiary of Celgene
• ClinicalTrials.gov Identifier: NCT02631044
• Other Study ID Numbers: 017001
• First Posted: Dec 15, 2015
• Last Update Posted: Aug 2, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• 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: JCAR017; chimeric antigen receptor; non-Hodgkin lymphoma; CAR; CAR T cells; autologous T cell therapy; cell therapy; NHL
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse

Study Results

No Results Posted as of Aug 2, 2022