Clinical Trials Register

Summary
EudraCT Number:	2018-004336-30
Sponsor's Protocol Code Number:	CYTB323A12101
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2019-10-21
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Austria - BASG

A.2

EudraCT number

2018-004336-30

A.3

Full title of the trial

Phase I/II, open label, multicenter study of rapcabtagene autoleucel in
adult patients with CLL/SLL, 3L+ DLBCL, r/r ALL and 1L HR LBCL.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Study of Rapcabtagene autoleucel (YTB323) in adult patients with
CLL/SLL, 3L+ DLBCL, r/r ALL and 1L HR LBCL.

A.4.1

Sponsor's protocol code number

CYTB323A12101

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Novartis Pharma AG
B.1.3.4	Country	Switzerland
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Novartis Pharma AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Pharma GmbH
B.5.2	Functional name of contact point	Drug Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	Jakov-Lind-Straße 5 / Top 3.05
B.5.3.2	Town/ city	Wien
B.5.3.3	Post code	1020
B.5.3.4	Country	Austria
B.5.4	Telephone number	+43 1 86657 0
B.5.5	Fax number	+43 1 86657 6458
B.5.6	E-mail	austria.dra@novartis.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Rapcabtagene autoleucel
D.3.2	Product code	YTB323
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Rapcabtagene autoleucel
D.3.9.2	Current sponsor code	YTB323
D.3.9.4	EV Substance Code	SUB198391
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	2500000 to 40000000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	Yes
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	Yes
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	IMBRUVICA
D.2.1.1.2	Name of the Marketing Authorisation holder	Janssen-Cilag International NV
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	CLL: EU/3/12/984
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	IBRUTINIB
D.3.9.1	CAS number	936563-96-1
D.3.9.3	Other descriptive name	Imbruvica
D.3.9.4	EV Substance Code	SUB120863
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	140
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

ALL, CLL/SLL and DLBCL and High-Risk LBCL.

E.1.1.1

Medical condition in easily understood language

acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and diffuse large B-cell lymphoma (DLBCL) and High-Risk large B-cell lymphoma (HR LBCL).

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Phase I
- Dose recommendation
- Safety
- Tolerability
- Manufacture success

Phase II - DLBCL and HR LBCL cohorts only:
- Antitumor activity of rapcabtagene autoleucel single agent

E.2.2

Secondary objectives of the trial

- Cellular kinetics
- Immunogenicity
- Tumor response in CLL/SLL
- Tumor response in DLBCL
- Tumor response in ALL
- Tumor response in HR LBCL
- Safety

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•≥ 18 years old
• For ALL and DLBCL: ECOG 0-1
• For HR LBCL: ECOG 0-2
• DLBCL:
- Diagnosis by local histopathology
- Relapsed or refractory disease having received 2 or more lines of systemic therapy, including anti-CD20 and anthracycline-based chemotherapy, and either having progressed (or relapsed) after autologous HSCT, or being ineligible for or not consenting to the procedure.
•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)
•ALL relapsed or refractory including at least 1 of the following: after allogeneic HSCT, after 2 or more lines of treatment, primary refractory disease, first relapse occurring within 12 months from first remission; patients with Philadelphia chromosome-positive ALL must have failed at least 2 different tyrosine kinase inhibitors or are intolerant
HR LBCL cohort:
- Histologically confirmed large B-cell non-Hodgkin lymphoma.
- Considered to be high-risk (IPI 3-5, MYC and BCL2 and/or BCL6 (DH/TH)).
- Participants must have received 2 cycles of frontline therapy for LBCL (R-CHOP, Pola-R-CHP, DA-EPOCH-R). Participants with DH/TH lymphoma must have received at least one cycle (the most recent cycle) of DAEPOCH-R.

E.4

Principal exclusion criteria

• Prior CD19-directed therapy with the exception of blinatumomab for patients with ALL
• Prior administration of a genetically engineered cellular product
• Prior allogeneic HSCT (CLL and DLBCL only)
• Richter's transformation
• Uncontrolled seizure disorder
• History of deep venous thrombosis or pulmonary embolus
• For DLBCL: Primary Central Nervous System (CNS) lymphoma or DLBCL with active CNS involvement, except if CNS involvement has been effectively treated and provided that treatment was > 4 weeks before screening.
• For HR LBCL:
-Active CNS involvement by malignancy
-Patients who are candidates for abbreviated (<6 cycles) CIT with or without consecutive radiotherapy
• For ALL:
-presence of CNS-2 disease with neurological changes or CNS-3 disease
-ALL that has evolved from an antecedent myeloid neoplasm or that harbors evidence of de novo presentation of a lymphoid blast phase of a previously undiagnosed myeloid neoplasm.

E.5 End points

E.5.1

Primary end point(s)

- Incidence and nature of Dose Limiting Toxicities (Dose Escalation part only)
- Incidence and severity of AEs and SAEs, including changes in laboratory values, ECG and vital signs
- Ibrutinib dose modifications in the CLL/SLL arm
- Number of patients infused with planned target dose
Phase II part - DLBCL:
- CRR defined as BOR of CR after rapcabtagene infusion
Phase II part - HR LBCL:
- CRR defined as BOR of CR after rapcabtagene infusion

E.5.1.1

Timepoint(s) of evaluation of this end point

24 months.

E.5.2

Secondary end point(s)

• CAR transgene levels by quantitative polymerase chain reaction
(qPCR) in peripheral blood, bone marrow and lymph nodes
• Cellular and humoral responses to the CAR transgene
• BOR as CR/PR per iwCLL response criteria, DOR
• Disease response (CR/PR) per Lugano criteria, DOR, OS
• BOR as CR/CRi, disease response (CR/CRi), DOR, EFS, OS, MRD status
Phase II part - DLBCL:
- Overall response rate (ORR) defined as BOR of CR/PR as per Lugano criteria
- CRR at months 3 and 6
- Duration of response (DOR), defined as time from first CR/PR to first documented progression or death due to any cause
- Progression-free survival (PFS) defined as time from rapcabtagene autoleucel infusion to first documented progression or death due to any cause
- Overall survival (OS), defined as time from date of rapcabtagene autoleucel infusion to date of death due to any cause
Phase II part - HR LBCL:
- Overall response rate (ORR) defined as BOR of CR/PR as per Lugano criteria
- CRR at months 6 and 12
- Duration of response (DOR). defined as time from first CR/PR to first documented progression or death due to any cause
- Progression-free survival (PFS) defined as time from rapcabtagene autoleucel infusion to first documented progression or death due to any cause
- Event-free survival (EFS\ defined as time from rapcabtagene autoleucel infusion to first documented progression, start of new anti-lymphoma therapy, biopsy-proven residual disease on or after month 6, or death due to any cause
- Overall survival (OS), defined as time from date of rapcabtagene autoleucel infusion to date of death due to any cause

E.5.2.1

Timepoint(s) of evaluation of this end point

24 months

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

Yes

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Japan

United States

Austria

France

Germany

Italy

Spain

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

120

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

120

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

128

F.4.2.2

In the whole clinical trial

240

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

All subjects who either complete or prematurely discontinue from the study will be enrolled in a Long Term Follow Up destination protocol. Evaluations will be performed for up to 15 years from the date of infusion

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-02-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-04-07

P. End of Trial
P.	End of Trial Status	Ongoing

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials