Study to Assess Change in Disease Activity and Adverse Events of Oral Venetoclax With Intravenous (IV) Obinutuzumab in Adult Participants With Recurring Chronic

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AbbVie Deutschland GmbH & Co. KG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

29 Mar 2022 → ongoing

Decision date (initial)

2023-11-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

F. Hoffmann-La Roche Ltd · AbbVie Inc.

External identifiers

EU CT number

2023-504599-10-00

EudraCT number

2021-001037-39

ClinicalTrials.gov

NCT04895436

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

The primary objective of the study is to assess the efficacy of VenG retreatment in Cohort 1.
The corresponding primary estimand is the ORR achieved by "all treated subjects" in Cohort 1 by their EOCT assessment (i.e., EOCT + 3 months, or "EOCT + 3").

Secondary objectives 4

1. The secondary efficacy objective is to quantify the efficacy of treatment with VenG in Cohort 1 via the secondary endpoints specified.
2. No hypothesis testing framework or any formal statistical comparisons will be conducted during this study.
3. Appropriate summaries including descriptive statistics and CIs will serve as the basis for our analysis.
4. Assessing the safety of retreatment with VenG is also a secondary objective of this study.

Conditions and MedDRA coding

Chronic lymphocytic leukemia recurrent

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Subjects must voluntarily sign and date an informed consent, approved by an independent ethics committee (IEC)/institutional review board (IRB), prior to the initiation of any screening or study-specific procedures.
2. Documented diagnosis of CLL that requires retreatment according to iwCLL criteria.
3. Previously completed venetoclax + anti-CD20 antibody ± X (where X is any additional drug) regimen as 1L fixed duration therapy and achieved documented response, defined as CR, CRi, PR, or nPR. Subjects who stopped 1L therapy earlier but completed at least 9 months of therapy and had a documented clinical response may be eligible based on the investigator's discretion. In Cohort 1, a maximum of approximately 20 subjects who previously received rituximab in 1L may be enrolled; in Cohort 2, there is no maximum number of subjects who previously received rituximab.
4. Patients who will not receive approved second-line therapies as assessed by the investigator and patient preference may be eligible for the study.
5. a) For Cohort 1: More than 24 months between the last dose of venetoclax and progression requiring treatment after completion of 1L venetoclax + anti-CD20 antibody ± X treatment; b) for Cohort 2: 12- 24 months between the last dose of venetoclax and progression requiring treatment after completion of 1L venetoclax + anti-CD20 antibody ± X treatment.
6. Subject has not received an intervening treatment for CLL after completing previous treatment with venetoclax + anti-CD20 antibody ± X.
7. Subject has not discontinued prior venetoclax + anti-CD20 antibody ± X treatment due to PD during treatment.
8. No active or uncontrolled autoimmune hemolytic anemia or immune thrombocytopenic purpura.
9. No transformation of CLL to aggressive NHL (Richter's transformation or pro-lymphocytic leukemia).
10. Subjects must not be incarcerated and must be freely willing and able to provide informed consent (e.g., adults under legal protection measure [e.g., under guardianship/curatorship] or unable to express their consent and select adults under psychiatric care). Investigator's discretion should be applied.

Exclusion criteria 1

1. NA

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. The primary efficacy endpoint is the overall response of CR, CRi, nPR, or PR in Cohort 1 subjects as assessed by the investigator at the EOCT, evaluated 3 months after the EOCT with VenG (EOCT + 3, i.e., Cycle 9).
2. Disease assessments will be based on the 2018 International Workshop for Chronic Lymphocytic Leukemia criteria for tumor response.
3. Overall response rate is defined as the proportion of subjects achieving a best response of CR, CRi, nPR, or PR.

Secondary endpoints 9

1. Overall response of CR or CRi at end of treatment assessment (EOT, assessed at EOT + 3)
2. Overall response of CR, CRi, nPR, or PR at EOT (assessed at EOT + 3)
3. Time to response (TTR)
4. Duration of response (DOR)
5. Time to next treatment (TTNT) for CLL
6. Progression-free survival (PFS)
7. Overall survival (OS)
8. uMRD rate (< 10-4) at EOCT, measured in PB (assessed at EOCT+ 3)
9. uMRD rate (< 10-4) at EOT, measured in PB (assessed at EOT + 3)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AbbVie Deutschland GmbH & Co. KG

Sponsor organisation

AbbVie Deutschland GmbH & Co. KG

Address

Mainzer Strasse 81

City

Wiesbaden

Postcode

65189

Country

Germany

Scientific contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinial Trial Helpdesk

Public contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinial Trial Helpdesk

Third parties 5

Locations

6 EU/EEA countries · 26 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 36 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

13 submissions — initial application plus substantial / non-substantial modifications