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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03960840




Registration number
NCT03960840
Ethics application status
Date submitted
21/05/2019
Date registered
23/05/2019

Titles & IDs
Public title
Phase I/II Study of Rapcabtagene Autoleucel in CLL, 3L+ DLBCL, ALL and 1L HR LBCL
Scientific title
Phase I/II, Open Label, Multicenter Study of Rapcabtagene Autoleucel in Adult Patients With CLL/SLL, 3L+ DLBCL, ALL and 1L HR LBCL
Secondary ID [1] 0 0
CYTB323A12101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Lymphocytic Leukemia 0 0
Small Lymphocytic Lymphoma 0 0
Diffuse Large B-cell Lymphoma 0 0
Acute Lymphoblastic Leukemia 0 0
Large B-cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Rapcabtagene autoleucel single agent
Treatment: Drugs - Ibrutinib

Experimental: CLL/SLL - Dose escalation and expansion of rapcabtagene autoleucel in combination with ibrutinib

Experimental: 3L+ DLBCL - Dose escalation and expansion of rapcabtagene autoleucel single agent in 3L+ DLBCL

Experimental: Adult ALL - Dose escalation and expansion of rapcabtagene autoleucel single agent in adult ALL

Experimental: 1L HR LBCL - Rapcabtagene autoleucel single agent in 1L HR LBCL


Treatment: Other: Rapcabtagene autoleucel single agent
Single infusion of rapcabtagene autoleucel

Treatment: Drugs: Ibrutinib
Tablets or capsules for oral daily use

Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1: Dose recommendation: Incidence and nature of Dose Limiting Toxicities (Dose Escalation part only)
Timepoint [1] 0 0
28 days
Primary outcome [2] 0 0
Phase 1: Safety: Incidence and severity of AEs and SAEs, including changes in laboratory values, ECG and vital signs
Timepoint [2] 0 0
24 months
Primary outcome [3] 0 0
Phase 1: Tolerability: Ibrutinib dose modifications in the CLL/SLL arm
Timepoint [3] 0 0
24 months
Primary outcome [4] 0 0
Phase 1: Manufacture success: Number of patients infused with planned target dose
Timepoint [4] 0 0
24 months
Primary outcome [5] 0 0
Phase 2: Complete Response Rate (CRR) as assessed by local Investigator
Timepoint [5] 0 0
24 months
Secondary outcome [1] 0 0
Phase 1: Complete Response (CR)/Partial Response (CR) in CLL/SLL
Timepoint [1] 0 0
24 months
Secondary outcome [2] 0 0
Phase 1: BOR of CR/PR per Lugano criteria in 3L+ DLBCL
Timepoint [2] 0 0
24 months
Secondary outcome [3] 0 0
Phase 1: Duration of response (DOR) in CLL/SLL and 3L+ DLBCL
Timepoint [3] 0 0
24 months
Secondary outcome [4] 0 0
Phase 1: BOR in ALL as assessed by an Independent Review Committee (IRC)
Timepoint [4] 0 0
month 3
Secondary outcome [5] 0 0
Phase 1: DOR in ALL as assessed by an Independent Review Committee
Timepoint [5] 0 0
24 months
Secondary outcome [6] 0 0
Phase 1: EFS in ALL as assessed by an Independent Review Committee
Timepoint [6] 0 0
24 months
Secondary outcome [7] 0 0
Phase 1: BOR in ALL as assessed by local Investigator
Timepoint [7] 0 0
24 months
Secondary outcome [8] 0 0
Phase 1: DOR in ALL as assessed by local Investigator
Timepoint [8] 0 0
24 months
Secondary outcome [9] 0 0
Phase 1: EFS in ALL as assessed by local Investigator
Timepoint [9] 0 0
24 months
Secondary outcome [10] 0 0
Phase 1: Overall survival in adult ALL
Timepoint [10] 0 0
24 months
Secondary outcome [11] 0 0
Phase 1: MRD negative status by flow cytometry in adult ALL
Timepoint [11] 0 0
24 months
Secondary outcome [12] 0 0
Phase 1: Quality of life in adult ALL patients enrolled in the expansion part by use of Electronic Patient Reported Outcomes (ePRO) as per EORTC QLQ-C30 questionnaire
Timepoint [12] 0 0
24 months
Secondary outcome [13] 0 0
Phase 1: Quality of life in adult ALL patients enrolled in the expansion part by use of Electronic Patient Reported Outcomes (ePRO) as per EQ-5D-3 questionnaire
Timepoint [13] 0 0
24 months
Secondary outcome [14] 0 0
Phase 1/2: Cellular kinetics
Timepoint [14] 0 0
24 months
Secondary outcome [15] 0 0
Phase 1/2: Immunogenicity
Timepoint [15] 0 0
24 months
Secondary outcome [16] 0 0
Phase 2: Overall response rate (ORR)
Timepoint [16] 0 0
24 months
Secondary outcome [17] 0 0
Phase 2: Complete Response Rate (CRR)
Timepoint [17] 0 0
months 3, 6
Secondary outcome [18] 0 0
Phase 2: Complete Response Rate (CRR)
Timepoint [18] 0 0
months 6, 12
Secondary outcome [19] 0 0
Phase 2: Duration of response (DOR)
Timepoint [19] 0 0
24 months
Secondary outcome [20] 0 0
Phase 2: Progression-free survival (PFS)
Timepoint [20] 0 0
24 months
Secondary outcome [21] 0 0
Phase 2: Event-free survival (EFS)
Timepoint [21] 0 0
24 months
Secondary outcome [22] 0 0
Phase 2: Overall survival (OS)
Timepoint [22] 0 0
24 months
Secondary outcome [23] 0 0
Phase 2: Complete Response Rate (CRR) in subgroups 1) IPI 4-5 or DH/TH and 2) IPI 3 and not DH/TH
Timepoint [23] 0 0
months 6, 12
Secondary outcome [24] 0 0
Phase 2: Overall response rate (ORR) in subgroups 1) IPI 4-5 or DH/TH and 2) IPI 3 and not DH/TH
Timepoint [24] 0 0
24 months
Secondary outcome [25] 0 0
Phase 2: Duration of response (DOR) in subgroups 1) IPI 4-5 or DH/TH and 2) IPI 3 and not DH/TH
Timepoint [25] 0 0
24 months
Secondary outcome [26] 0 0
Phase 2: Progression-free survival (PFS) in subgroups 1) IPI 4-5 or DH/TH and 2) IPI 3 and not DH/TH
Timepoint [26] 0 0
24 months
Secondary outcome [27] 0 0
Phase 2: Event-free survival (EFS) in subgroups 1) IPI 4-5 or DH/TH and 2) IPI 3 and not DH/TH
Timepoint [27] 0 0
24 months
Secondary outcome [28] 0 0
Phase 2: Overall survival (OS) in subgroups 1) IPI 4-5 or DH/TH and 2) IPI 3 and not DH/TH
Timepoint [28] 0 0
24 months
Secondary outcome [29] 0 0
Phase 2: Manufacturing vein to door time
Timepoint [29] 0 0
24 months

Eligibility
Key inclusion criteria
* ECOG performance status 0-1
* CLL or SLL diagnosis according to iwCLL criteria
* CLL/SLL in SD or PR after at least 6 months of ibrutinib, either as second or subsequent line of therapy
* DLBCL diagnosis by local histopathology
* DLBCL relapsed or refractory after 2 or more lines of therapy, including autologous hematopoietic stem cell transplantation (HSCT)
* Refractory or relapsed CD19-positive ALL
* ALL with morphologic disease in the bone marrow

1L HR LBCL - Considered to be high-risk based on at least 1 of the following at diagnosis:
* IPI score of 3, 4 or 5
* MYC and BCL2 and/or BCL6 rearrangement (DH/THL)
* Participants must have received 2 cycles of frontline therapy for LBCL with R-CHOP or Pola-R-CHP or DA-EPOCH-R. Participants with DH/TH lymphoma must have received DA-EPOCH-R.
* Participants must have a positive PET per Lugano classification (Deauville PET score of 4 or 5 and an overall response of PR/SD) after 2 cycles of frontline CIT. Note: Patient's with Deauville PET score of 5 and overall response of PD, or with Deauville PET score of 1, 2, or 3 and overall response of CR, are not eligible for this trial.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior CD19-directed therapy
* Prior administration of a genetically engineered cellular product
* Prior allogeneic HSCT
* Richter's transformation

* For 1L HR LBCL: Richter's transformation, Burkitt lymphoma, primary DLBCL of CNS, DLBCL associated with chronic inflammation, intravascular large B-cell lymphoma, ALK- positive large B-cell lymphoma, HHV8 positive LBCL, DLBCL leg type or EBV positive DLBCL, NOS.
* Active CNS lymphoma

* For 1L HR LBCL: Active CNS involvement by malignancy
* Targeted small molecule or kinase inhibitor within 2 weeks from leukapheresis

Other protocol-defined inclusion/exclusion may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment postcode(s) [2] 0 0
3004 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Kansas
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
United States of America
State/province [10] 0 0
Texas
Country [11] 0 0
United States of America
State/province [11] 0 0
Wisconsin
Country [12] 0 0
Austria
State/province [12] 0 0
Wien
Country [13] 0 0
France
State/province [13] 0 0
Marseille
Country [14] 0 0
France
State/province [14] 0 0
Paris 10
Country [15] 0 0
France
State/province [15] 0 0
Pierre Benite
Country [16] 0 0
Germany
State/province [16] 0 0
Essen
Country [17] 0 0
Germany
State/province [17] 0 0
Frankfurt
Country [18] 0 0
Germany
State/province [18] 0 0
Koeln
Country [19] 0 0
Germany
State/province [19] 0 0
Leipzig
Country [20] 0 0
Italy
State/province [20] 0 0
BG
Country [21] 0 0
Italy
State/province [21] 0 0
BO
Country [22] 0 0
Italy
State/province [22] 0 0
MI
Country [23] 0 0
Japan
State/province [23] 0 0
Fukuoka
Country [24] 0 0
Japan
State/province [24] 0 0
Hokkaido
Country [25] 0 0
Japan
State/province [25] 0 0
Tokyo
Country [26] 0 0
Spain
State/province [26] 0 0
Andalucia
Country [27] 0 0
Spain
State/province [27] 0 0
Castilla Y Leon
Country [28] 0 0
Spain
State/province [28] 0 0
Catalunya
Country [29] 0 0
Spain
State/province [29] 0 0
Comunidad Valenciana
Country [30] 0 0
Spain
State/province [30] 0 0
Barcelona
Country [31] 0 0
Spain
State/province [31] 0 0
Madrid

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.