GIVE trial (Gazyvaro In combination with VEnetoclax in Elderly CLL)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 Oct 2016 → 21 Aug 2025

Decision date (initial)

2024-05-28

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Dutch Cancer Society · Roche

External identifiers

EU CT number

2024-511048-22-00

EudraCT number

2015-004985-27

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Others, Therapy

To separately study the efficacy, defined as MRD negative bone marrow and no progression according to the IWCLL criteria, of the two arms of the study of either venetoclax maintenance or MRD-guided venetoclax maintenance after sequential regimens of obinutuzumab (pre-induction) followed by 6 cycles obinutuzumab with venetoclax and 6 cycles of venetoclax (induction) in first-line patients with CLL and unfit for FCR like regimens.

Secondary objectives 4

1. To determine efficacy as assessed by additional outcome measures, including overall response, PFS, event free survival (EFS), OS
2. To determine the impact of the study treatment on quality of life and geriatric scores (including a biological senescence marker of skin biopsy)
3. Toxicity of venetoclax after pre-induction, especially tumorlysis and neutropenia
4. To identify predictive factors for response and resistance mechanisms

Conditions and MedDRA coding

Chronic lymphocytic leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Diagnosis of symptomatic CLL (according to IWCLL guidelines)
2. Patients without prior treatment for CLL (Corticoid treatment administered due to necessary immediate intervention is allowed; within the last 10 days before start of study treatment only dose equivalents of max 20 mg prednisolone are permitted)
3. Patients older than 18 years, not fit tor FCR-like regimens
4. Able to adhere to the study visit schedule and other protocol requirements
5. WHO performance status of <= 2
6. absolute neutrophil count >= 1.0 x 109/l and platelet count >= 50 x 109/l unless due to bone marrow infiltration
7. creatinine clearance>= 45 ml/min
8. total bilirubin <= 1,5 x ULN unless considered due to Gilbert's syndrome
9. transaminases <= 3 x ULN
10. Negative serum or urine pregnancy test within 28 days prior to registration (all females of childbearing potential)
11. Written informed consent
12. Patient is capable of giving informed consent

Exclusion criteria 21

1. Current inclusion in other clinical trials
2. lntolerance of exogenous protein administration
3. History of severe allergie or anaphylactic reactions to humanized or murine monoclonal antibodies. Known sensitivity or allergy to murine products
4. Hepatitis B virus (HBV): Patients with positive serology for hepatitis B defined as positivity for hepatitis B surface antigen (HBsAg) or hepatitis B care antibody (anti-HBc).
5. Hepatitis C virus (HCV): Patients with positive hepatitis C serology unless HCV- (RNA) is confirmed negative
6. HIV positive patients
7. Active fungal, bacterial, and/or viral infection that requires systemic therapy
8. Vaccination with a live vaccine a minimum of 28 days prior to registration
9. Use of any other experimental drug or therapy within 28 days of baseline
10. Concurrent use of other anti-cancer agents or treatments
11. History of prior malignancy, except for conditions as listed below if patients have recovered from the acute side effects incurred as a result of previous therapy
12. Malignancies surgically treated with curative intent and with no known active disease present for 3 years before randomization
13. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
14. Adequately treated cervical carcinoma in situ without evidence of disease
15. Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemie heart disease) (CTCAE grade 111-IV)
16. Severe pulmonary dysfunction (CTCAE grade 111-IV)
17. Severe neurological or psychiatrie disease (CTCAE grade 111-IV)
18. Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, hypertension, hyperthyroidism or hypothyroidism, etc.)
19. Wamen who are pregnant or lactating
20. Fertile men or women of childbearing potential unless: (1). surgically sterile or >= 2 years after the onset of menopause (2). willing to use a highly effective contraceptive method (Pearl Index <1) during study treatment and in female patients for 18 months after end of antibody treatment and male patients for 6 months after end of treatment
21. Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. MRD negative bone marrow after maximum 24 cycles of (planned) venetoclax and no progression according to IWCLL criteria at any earlier timepoint

Secondary endpoints 10

1. Efficacy as assessed by additional outcome measures, including overall response, PFS, EFS and OS
2. MRD in blood
3. Toxicity of venetoclax after pre-induction, especially tumorlysis and neutropenia
4. Quality of life
5. Geriatric assessment
6. P16 expression in skin biopsy
7. Predictive factors for response and resistance mechanisms: NGS at baseline and at progression
8. Predictive factors for response and resistance mechanisms: Flow-based subset analysis on expression levels of Bcl-2 proteins at baseline, during therapy and at progression
9. Predictive factors for response and resistance mechanisms: Analyses of malignant and non-malignant immune cells in PB and in LN at baseline and during treatment
10. Relationship between MRD dynamics and T cell diversity and/or function (amendment December 2021)

Investigational products

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

Test 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Sponsor organisation

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Address

Dr. Molewaterplein 40

City

Rotterdam

Postcode

3015 GD

Country

Netherlands

Scientific contact point

Organisation

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Contact name

Dr. A.P. Kater

Public contact point

Organisation

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Contact name

HOVON

Third parties 3

Locations

1 EU/EEA country · 25 investigational sites

By country

Investigational sites

Country notifications

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

Application history

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