A study to determine the efficacy and safety of JCAR017 in adult participants with aggressive B-cell non-Hodgkin lymphoma

Austria, Belgium, Finland, France, Germany, Italy, Japan, Netherlands, Spain, Switzerland, United Kingdom (ICTRP)

ID di studio ICTRP
EUCTR2017-000106-38 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
non disponibile

Titolo accademico
A Phase 2, Single-arm, Multi-cohort, Multi-center Trial to Determine the Efficacy and Safety of JCAR017 in Adult Subjects with Aggressive B-Cell Non-Hodgkin Lymphoma (TRANSCEND WORLD) (ICTRP)

Titolo pubblico
A study to assess the efficacy and safety of JCAR017, a CAR-T cell therapy, in adults with aggressive B-Cell Non-Hodgkin Lymphoma (ICTRP)

Malattie studiate
Aggressive B-cell Non Hodgkin Lymphoma (B-NHL)
MedDRA version: 23.0Level: LLTClassification code 10029593Term: Non-Hodgkin's lymphoma NOSSystem Organ Class: 100000004864
MedDRA version: 20.0Level: HLGTClassification code 10025320Term: Lymphomas non-Hodgkin's B-cellSystem Organ Class: 10005329 - Blood and lymphatic system disorders;Therapeutic area: Diseases [C] - Immune System Diseases [C20] (ICTRP)

Intervento studiato

Product Name: Lisocabtagene maraleucel
Product Code: JCAR017
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: LISOCABTAGENE MARALEUCEL
Current Sponsor code: JCAR017
Concentration unit: Other
Concentration type: equal
Concentration number: 1-

(ICTRP)

Tipo di studio
Interventional clinical trial of medicinal product (ICTRP)

Disegno dello studio
Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: Placebo: Other: Number of treatment arms in the trial: 1 (ICTRP)

Criteri di inclusione/esclusione
Gender:
Female: yes
Male: yes

Inclusion criteria:
1. Subject is = 18 years of age at the time of signing the informed consent form (ICF).

2. Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.

3. Subject is willing and able to adhere to the study visit schedule and other protocol requirements.

4. Investigator considers the subject is appropriate for adoptive T cell therapy.

5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Subjects not eligible for transplant (TNE) in Cohorts 2 and 3 and subjects in Cohort 5 may be enrolled with ECOG of 2 only if they meet all other inclusion/exclusion criteria.

6. Subjects with one of the following:
? Cohort 1: Subjects with DLBCL NOS (de novo or tFL), HGBL and FL3B per WHO 2016 classification (Swerdlow, 2016), after = 2 lines of therapy*, including an anthracycline and rituximab (or other CD20-targeted agent)
? Cohort 2: Transplant not eligible subjects with DLBCL NOS (de novo or tFL), HGBL and FL3B per WHO 2016 classification (Swerdlow, 2016), who failed first line therapy*, including an anthracycline and rituximab (or other CD20-targeted agent)
- Transplant not eligible subjects will include those who are deemed ineligible for high-dose chemotherapy and HSCT due to age, performance status or comorbidity, while also having adequate organ function for CAR T cell treatment. At the very least, subjects have to meet one of the following criteria:
a) Age = 70 years
b) ECOG performance status = 2
c) Impaired pulmonary function (DLCO = 60%, adjusted for hemoglobin concentration using the Dinakara equation)
d) Impaired cardiac function (LVEF < 50%)
e) Impaired renal function (CrCl < 60 mL/min)
f) Impaired hepatic function (AST/ALT > 2 x ULN, bilirubin = 2 mg/dL or cirrhosis Child-Pugh B or C)
- Subjects must fulfill all other inclusion and exclusion criteria
? Cohort 3: (Japan only): Subjects meeting eligibility criteria for either Cohort 1 or 2
? Cohort 4: Subjects with newly diagnosed HGBL. Subjects must be eligible for anthracycline and rituximab (or other CD20-targeted agent)-containing regimen as induction prior to consolidation with JCAR017**
? Cohort 5: Subjects with PCNSL who failed first line therapy with HDCT and ASCT or who failed to proceed to HDCT and ASCT due to failure of
PBSC mobilization or insufficient response at the completion of induction
therapy with high-dose methotrexate-based polychemotherapy regimen
(eg, high dose methotrexate, high dose cytarabine, rituximab and
thiotepa [MATRix regimen])

? Cohort 6: REMOVED
? Cohort 7: Subjects meeting eligibility criteria for Cohort 1 and suitable for outpatient treatment***
* For subjects with transformed disease, the subject should have had at least 2 lines of systemic therapy for his/her transformed disease (ie, DLBCL) for Cohort 1 and 1 line for Cohort 2 to be eligible. Lines of therapy do not include those given for a previously indolent condition (ie, follicular lymphoma). Subjects do NOT have to have anthracycline for their DLBCL if received for indolent disease.
** For subjects already undergoing anthracycline and rituximab-containing regimen, eligibility is to be discussed with the Medical Monitor. Subjects with complete metabolic response after 2 cycles of induction will proceed with JCAR017 infusion only at time of relapse, if applicable.
*** Subjects must meet the conditions for outpatient treatment and monitoring as outlined in the Outpatient Administration and Monitor (ICTRP)

Exclusion criteria:
1. Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.

2. Subject has any condition including the presence of laboratory abnormalities, which would place the subject at unacceptable risk if participating in the study.

3. Subject has any condition that confounds the ability to interpret data from the study.

4. Subjects with T cell rich/histiocyte rich large B-cell lymphoma (THRBCL), primary cutaneous large B-cell lymphoma, primary mediastinal B-cell lymphoma (PMBCL), Epstein-Barr virus (EBV) positive DLBCL of the elderly, Burkitt lymphoma, and intraocular lymphoma.

5. Subjects with prior history of malignancies, other than aggressive r/r NHL, unless the subject has been in remission for = 2 years with the exception of the following noninvasive 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

6. Treatment with any prior gene therapy product.

7. Subjects who have received previous CD19-targeted therapy.

8. Human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C:
? Subjects with a history of or active HIV are excluded
? Subjects with active hepatitis B, or active hepatitis C are excluded
- Subjects with a negative polymerase chain reaction (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

9. 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.

10. Presence of acute or chronic graft-versus-host disease (GVHD).

11. Active autoimmune disease requiring immunosuppressive therapy.

12. History of any one of the following cardiovascular conditions within the past 6 months:
? Heart failure class III or IV as defined by the New York Heart Association (NYHA)
? Cardiac angioplasty or stenting
? Myocardial infarction
? Unstable angina
? Other clinically significant cardiac disease

13. History or presence of clinically relevant CNS pathology not related to disease under study such as epilepsy, seizure, aphasia, stroke, cerebral edema, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.

14. Pregnant or nursing women.

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

16. Use of the following (see Section 8.2 for full details):
? Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or equivalent) within 7 days prior to leukapheresis or
72 hours prior to JCAR017 infusion. Physiologic replacement, topical, and inhaled steroids are permitted.
? Low-dose chemotherapy (eg, vincristine, rituximab, cyclophosphamide = 300 mg/m2) given after leukapheresis to maintain disease control must be stopped = 7 days prior to LD chemotherapy.
? Cytotoxic chemotherapeutic agents

Endpoint primari e secondari
Main Objective: Cohorts 1, 2, 3, 4, and 5:
- Determine the efficacy, defined as overall response rate (ORR), of JCAR017 in subjects with aggressive B-cell non-Hodgkin lymphoma.

Cohort 7
- Evaluate the safety of JCAR017 treatment in subjects intended to be treated as outpatients.
;Secondary Objective: - To evaluate the safety and feasibility of administering JCAR017 (Cohorts 1, 2, 3, 4, 5)

- To determine the efficacy, defined as ORR of JCAR017 in subjects intended to be treated as outpatients (Cohort 7)

- To evaluate other measures of efficacy of JCAR017 ( e.g., complete response rate [CRR], event-free survival [EFS], progression-free survival [PFS], overall survival [OS], duration of response [DOR])

- To characterize the pharmacokinetic (PK) profile of JCAR017, in the peripheral blood measured using qqPCR detection for the JCAR017 vector sequence

- To describe changes in health-related quality of life (HRQoL) using the global health/QoL, fatigue, physical, and cognitive functioning subscales of European Organisation for Research and Treatment of Cancer ? Quality of Life C30 questionnaire (EORTC QLQ-C30) and the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) "Additional concerns" scale (FACT-LymS);Primary end point(s): - Non-Hodgkin lymphoma (NHL; including secondary central nervous system [CNS] involvement): Overall Response Rate (ORR)
Cohorts 1, 2, 3 and 4

- Relapsed/refractory (r/r) primary central nervous system lymphoma (PCNSL): ORR
Cohort 5

- Safety in subjects intended to be treated as outpatients
Cohort 7
;Timepoint(s) of evaluation of this end point: Up to 2 years after JCAR017 infusion (ICTRP)

Secondary end point(s): - Safety
- Safety in subjects treated as outpatients
- ORR in subjects intended to be treated as outpatients Cohort 7
- Complete response rate (CRR)
- Event-free survival (EFS)
- Progression-free survival (PFS)
- Overall survival (OS)
- Duration of response (DOR)
- Pharmacokinetics (PK) by qPCR
- Health Related Quality of Life (domain of interest);Timepoint(s) of evaluation of this end point: Up to 2 years after JCAR017 infusion
For overall survival (OS) - up to last subject last visit (ICTRP)

Data di registrazione
19.03.2018 (ICTRP)

Inclusione del primo partecipante
06.11.2018 (ICTRP)

Sponsor secondari
non disponibile

Contatti aggiuntivi
ClinicalTrialDisclosure, ClinicalTrialDisclosure@celgene.com, +19137096862, Celgene Corporation (ICTRP)

ID secondari
JCAR017-BCM-001, 2017-000106-38-BE (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-000106-38 (ICTRP)