A Study to Evaluate the Safety and Efficacy of JCAR017 in Pediatric Subjects With Relapsed/Refractory (r/r) B-cell Acute Lymphoblastic Leukemia (B-ALL) and B-cell Non-Hodgkin Lymphoma (B-NHL)

NCT03743246 | Terminated Phase 1 Results DMC FDA Drug

• 3 other identifiers: JCAR017-BCM-004U1111-1220-33242018-001246-34
• Study Type: interventional
• Target: 21
• Locations: 6 countries
• Sites: 19

Brief Summary

This is a Phase 1/2, open-label, single arm, multicohort study to evaluate the safety and efficacy of JCAR017 in pediatric subjects aged ≤ 25 years with CD19+ r/r B-ALL and B-NHL. Phase 1 will identify a recommended Phase 2 dose (RP2D). Phase 2 will evaluate the efficacy of JCAR017 RP2D in the following three disease cohorts: Cohort 1 (r/r B-ALL), Cohort 2 (MRD+ B-ALL) and Cohort 3 (r/r B-NHL, \[DLBCL, BL, or PMBCL\]). A Simon's Optimal two-stage study design will be applied to Cohort 1 and 2 in Phase 2.

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin

Keywords

Pediatric; JCAR017; CAR-T; CART; CD19; ALL; NHL; DLBCL; BL; PMBCL; Cell Therapy; LisoCell; Young Adults; Lymphoproliferative disorders; Immune system diseases; Leukemia; Lymphoma; lymphatic diseases

Outcome Measures

Primary Outcomes (3)

• Number of Participants With Treatment Emergent Adverse Events up to 30 Days Post JCAR017 Infusion

  An AE is defined as any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. Treatment Emergent Adverse Events (TEAEs) are defined as any AE occurring or worsening on the day of the JCAR017 infusion until 30 days post-treatment (JCAR017 infusion) using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 or greater.

  From first JCAR017 infusion (Day 1) to 30 days after JCAR017 infusion

• Number of Participants With Dose Limiting Toxicities

  A DLT was defined as: * Death not related to disease progression * Grade (Gr) 4 (Life-threatening) neurotoxicity * Gr 3 (Severe) neurotoxicity of greater than 7 days * Gr 3 neurotoxicity does not revert to baseline within 28 days of the start date of the Grade 3 event * Seizures of grade that do not resolve within 7 days * Gr 4 cytokine release syndrome (CRS) that does not resolve to Grade ≤ 3 within 3 days * Gr 3 CRS that does not resolve to Grade ≤ 2 within 7 days * Any increase in aspartate aminotransferase (AST) or ALT \> 3 × ULN and concurrent increase in total bilirubin \> 2 × ULN that is unrelated to CRS and has no other probable reason to explain the combination of increases * Any cardiac, dermatologic, gastrointestinal, hepatic, pulmonary, renal/genitourinary, or neurologic Gr 3 or 4 event not pre-existing or not due to the underlying malignancy * Any other Gr 3 or 4 event deemed unexpected by the Investigator and considered a DLT upon evaluation by the safety review committee

  From first JCAR017 infusion (Day 1) to 28 days after JCAR017 infusion

• Concentration of JCAR017 in Peripheral Blood at Day 28 Post JCAR017 Infusion

  Concentration of JCAR017 in Peripheral Blood was assessed by droplet digital polymerase chain reaction.

  At day 28 post JCAR017 infusion

Secondary Outcomes (19)

• Number of Participants With Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion

  From first JCAR017 infusion (Day 1) to 90 days after JCAR017 infusion

• Number of Participants With Serious Treatment-Emergent Adverse Events up to 90 Days Post JCAR017 Infusion

  From first JCAR017 infusion (Day 1) to 90 days after JCAR017 infusion

• Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets

  Baseline and at Day 28

• Change From Baseline at Day 28 in Hematology Laboratory Parameters- Basophils/Leukocytes; Eosinophils/Leukocytes; Lymphocytes/Leukocytes; Neutrophils/Leukocytes; Monocytes/Leukocytes

  Baseline and at Day 28

• Change From Baseline at Day 28 in Hematology Laboratory Parameters- Erythrocytes

  Baseline and at Day 28

Study Arms (1)

Administration of JCAR017

EXPERIMENTAL

Subjects will receive Lymphodepleting chemotherapy with intravenous (IV) fludarabine (30 mg/m2/day for 3 days) plus cyclophosphamide IV (300 mg/m2/day for 3 days) (flu/cy) concurrently, followed by JCAR017 cells infusion. Phase 1 will evaluate up to 5 JCAR017 cells dose levels and dose escalation/de-escalation will follow a modified toxicity probability interval (mTPI-2) algorithm. The declared RP2D in Phase 1 will be applied to the subjects enrolled in Phase 2

Drug: JCAR017; Drug: Lymphodepleting; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

JCAR017 DRUG

JCAR017

Administration of JCAR017

Lymphodepleting DRUG

Lymphodepleting

Administration of JCAR017

Fludarabine DRUG

Fludarabine

Administration of JCAR017

Cyclophosphamide DRUG

Cyclophosphamide

Administration of JCAR017

Eligibility Criteria

• Age: Up to 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Subjects must satisfy the following criteria to be enrolled in the study:
• Phase 1: Subject \< 18 years of age and weighs ≥ 6 kg at the time of signing the informed consent form (ICF)/informed assent form (IAF).
• Phase 2: Subject ≤ 25 years of age and weighs ≥ 6 kg at the time of signing the ICF/IAF.
• Subject (when applicable, parental/legal representative) must understand and voluntarily provide permission to the ICF/IAF prior to conducting any study-related assessments/procedures.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
• Investigator considers the subject is appropriate for adoptive T cell therapy.
• Evidence of CD19 expression via flow cytometry (peripheral blood or bone marrow) or immunohistochemistry (bone marrow biopsy)
• Subject has a Karnofsky score of ≥ 50 (subjects ≥ 16 years of age) or a Lansky score ≥ 50 (subjects \< 16 years of age).
• Diagnosis of B-cell ALL or B-cell NHL as defined below:
• Phase 1: Subjects with r/r B-ALL, defined as morphological evidence of disease in BM (5% or greater lymphoblast by morphology) and either of the following:
• First or greater marrow relapse, or
• Any marrow relapse after allogeneic HSCT, or
• Primary refractory defined as not achieving a CR or a CRi after 2 or more separate induction regimens (or chemo-refractory as not achieving CR/CRi after 1 cycle of standard chemotherapy for relapsed leukemia), or
• Ineligible for allogeneic HSCT Note: Subjects will be included regardless of MRD status.
• Phase 2: Subjects with one of the following:

You may not qualify if:

• The presence of any of the following will exclude a subject from enrollment:
• Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
• 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.
• Subject has any condition that confounds the ability to interpret data from the study.
• Subject with a history of another primary malignancy that has not been in remission for at least 2 years prior to enrollment.
• Subjects who have received previous CD19-targeted therapy must have CD19-positive disease confirmed since completing the prior CD19-targeted therapy.
• Prior CAR T cell or other genetically-modified T cell therapy.
• Subject with a previous history of or active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection.
• Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment at the time of leukapheresis or JCAR017 infusion.
• Subject has presence of acute or chronic graft-versus-host disease (GVHD).
• Subject with active autoimmune disease requiring immunosuppressive therapy.
• Subject has cardiac disorders (CTCAE version 4.03 Grade 3 or 4) within the past 6 months.
• Subject with a concomitant genetic syndrome, with the exception of Down's syndrome.
• Subject with active CNS disease and significant neurological deterioration. Subjects with CNS-2 or CNS-3 involvement are eligible provided they are asymptomatic and do not have significant neurological deterioration and, in the opinion of the study investigator, the CNS disease burden can be controlled until JCAR017 infusion.
• Subject with a history or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, cerebral edema, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.

Sponsors & Collaborators

• Celgene: lead

Study Sites (19)

Local Institution - 163

Duarte, California, 91010, United States

Location

Local Institution - 167

Redwood City, California, 94063, United States

Location

Local Institution - 166

St. Petersburg, Florida, 33701, United States

Location

Local Institution - 160

New York, New York, 10021, United States

Location

Local Institution - 162

Philadelphia, Pennsylvania, 19104, United States

Location

Local Institution - 164

Dallas, Texas, 75390-7208, United States

Location

Local Institution - 165

Houston, Texas, 77030, United States

Location

Local Institution - 161

Seattle, Washington, 98105, United States

Location

Local Institution - 168

Wauwatosa, Wisconsin, 53226, United States

Location

Local Institution - 601

Lyon, 69008, France

Location

Local Institution - 602

Marseille, 13005, France

Location

Local Institution - 600

Paris, 75935, France

Location

Local Institution - 501

Berlin, 13353, Germany

Location

Local Institution - 500

Frankfurt, D-60590, Germany

Location

Local Institution - 301

Monza, 20900, Italy

Location

Local Institution - 300

Roma, 00165, Italy

Location

Local Institution - 400

Utrecht, 3584 CS, Netherlands

Location

Local Institution - 251

Esplugues de Llobregat, 08950, Spain

Location

Local Institution - 250

Madrid, 28009, Spain

Location

Related Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Non-Hodgkin; Lymphoproliferative Disorders; Immune System Diseases; Leukemia; Lymphoma; Lymphatic Diseases

Interventions

fludarabine; Cyclophosphamide

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Limitations and Caveats

The study was terminated and hence participants were not enrolled in Phase 2 cohorts (r/r B-ALL; MRD+ B-ALL; r/r B-NHL).

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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2018
• First Posted: November 16, 2018
• Study Start: October 17, 2018
• Primary Completion: January 26, 2024
• Study Completion: January 26, 2024
• Last Updated: August 15, 2024
• Results First Posted: August 15, 2024

Record last verified: 2024-07

Locations

ES (2); NL (1); FR (3); IT (2); US (9); DE (2)