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Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
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Register:
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ClinicalTrials.gov |
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Last refreshed on:
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18 March 2024 |
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Main ID: |
NCT02950051 |
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Date of registration:
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27/10/2016 |
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Prospective Registration:
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Yes |
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Primary sponsor: |
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Public title:
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Standard Chemoimmunotherapy (FCR/BR) Versus Rituximab + Venetoclax (RVe) Versus Obinutuzumab (GA101) + Venetoclax (GVe) Versus Obinutuzumab + Ibrutinib + Venetoclax (GIVe) in Fit Patients With Previously Untreated Chronic Lymphocytic Leukemia (CLL) Without Del(17p) or TP53 Mutation
GAIA |
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Scientific title:
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A Phase 3 Multicenter, Randomized, Prospective, Open-label Trial of Standard Chemoimmunotherapy (FCR/BR) Versus Rituximab Plus Venetoclax (RVe) Versus Obinutuzumab (GA101) Plus Venetoclax (GVe) Versus Obinutuzumab Plus Ibrutinib Plus Venetoclax (GIVe) in Fit Patients With Previously Untreated Chronic Lymphocytic Leukemia (CLL) Without Del(17p) or TP53 Mutation |
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Date of first enrolment:
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December 13, 2016 |
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Target sample size:
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926 |
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Recruitment status: |
Completed |
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URL:
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https://clinicaltrials.gov/ct2/show/NCT02950051 |
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Study type:
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Interventional |
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Study design:
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Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
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Phase:
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Phase 3
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Countries of recruitment
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Austria
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Belgium
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Denmark
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Finland
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Germany
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Ireland
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Israel
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Netherlands
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Sweden
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Switzerland
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Contacts
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Name:
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Barbara Eichhorst, MD, Prof. |
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Address:
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Telephone:
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Email:
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Affiliation:
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Department I of Internal Medicine, University Hospital Cologne |
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Key inclusion & exclusion criteria
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Inclusion Criteria:
1. Documented CLL requiring treatment according to iwCLL criteria
2. Age at least 18 years
3. Life expectancy = 6 months
4. Ability and willingness to provide written informed consent and to adhere to the study
visit schedule and other protocol requirements
5. Adequate bone marrow function indicated by a platelet count >30 x10^9/l (unless
directly attributable to CLL infiltration of the bone marrow, proven by bone marrow
biopsy)
6. Creatinine clearance =70ml/min directly measured with 24hr urine collection or
calculated according to the modified formula of Cockcroft and Gault (for men: GFR ˜
((140 - age) x bodyweight) / (72 x creatinine), for women x 0, 85). For patients with
creatinine values within the normal range the calculation of the clearance is not
necessary. Dehydrated patients with an estimated creatinine clearance less than 70
ml/min may be eligible if a repeat estimate after adequate hydration is > 70 ml/min
7. Adequate liver function as indicated by a total bilirubin= 2 x, AST/ALT = 2.5 x the
institutional ULN value, unless directly attributable to the patient's CLL or to
Gilbert's Syndrome
8. Negative serological testing for hepatitis B (HBsAg negative and anti-HBc negative;
patients positive for anti-HBc may be included if PCR for HBV DNA is negative and
HBV-DNA PCR is performed every month until 12 months after last treatment cycle),
negative testing for hepatitis C RNA within 6 weeks prior to registration
9. Eastern Cooperative Oncology Group Performance Status (ECOG) performance status 0-2
Exclusion Criteria:
1. Any prior CLL-specific therapies (except corticosteroid treatment administere due to
necessary immediate intervention; within the last 10 days before start of study
treatment, only dose equivalents of 20 mg prednisolone are permitted).
2. Transformation of CLL (Richter transformation)
3. Decompensated hemolysis, defined as ongoing hemoglobin drop in spite of three more
concurrent treatments being administered for hemolysis
4. Detected del(17p) or TP53 mutation
5. Patients with a history of PML
6. Any comorbidity or organ system impairment rated with a single CIRS (cumulative
illness rating scale) score of 4 (excluding the eyes/ears/nose/throat/larynx organ
system), a total CIRS score of more than 6 or any other life-threatening illness,
medical condition or organ system dysfunction that, in the investigator´s opinion,
could comprise the patients safety or interfere with the absorption or metabolism of
the study drugs (e.g, inability to swallow tablets or impaired resorption in the
gastrointestinal tract)
7. Urinary outflow obstruction
8. Malignancies other than CLL currently requiring systemic therapies, not being treated
in curative intention before (unless the malignant disease is in a stable remission
due to the discretion of the treating physician) or showing signs of progression after
curative treatment
9. Uncontrolled or active infection
10. Patients with known infection with human immunodeficiency virus (HIV)
11. Requirement of therapy with strong CYP3A4 and CYP3A5 inhibitors/inducers
12. Anticoagulant therapy with warfarin or phenoprocoumon, (rotation to alternative
anticoagulation is allowed, but note that patients being treated with NOAKs can be
included, but must be properly informed about the potential risk of bleeding under
treatment with ibrutinib)
13. History of stroke or intracranial hemorrhage within 6 months prior to registration
14. Use of investigational agents which might interfere with the study drug within 28 days
prior to registration
15. Vaccination with live vaccines 28 days prior to registration
16. Major surgery less than 30 days before start of treatment
17. History of severe allergic or anaphylactic reactions to humanized or murine monoclonal
antibodies, known sensitivity or allergy to murine products
18. Known hypersensitivity to any active substance or to any of the excipients of one of
the drugs used in the trial
19. Pregnant women and nursing mothers (a negative pregnancy test is required for all
women of childbearing potential within 7 days before start of treatment; further
pregnancy testing will be performed regularly)
20. Fertile men or women of childbearing potential unless:
1. surgically sterile or = 2 years after the onset of menopause
2. willing to use two methods of reliable contraception including one highly
effective contraceptive method (Pearl Index <1) and one additional effective
(barrier) method during study treatment and for 18 months after the end of study
treatment
21. Legal incapacity
22. Prisoners or subjects who are institutionalized by regulatory or court order
23. Persons who are in dependence to the sponsor or an investigator
Age minimum:
18 Years
Age maximum:
N/A
Gender:
All
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Health Condition(s) or Problem(s) studied
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Chronic Lymphocytic Leukemia
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Intervention(s)
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Drug: Venetoclax
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Biological: Obinutuzumab
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Biological: Rituximab
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Drug: Cyclophosphamide
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Drug: Ibrutinib
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Drug: Bendamustine
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Drug: Fludarabine
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Primary Outcome(s)
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Miminimal residual disease (MRD) negativity rate in peripheral blood (PB)
[Time Frame: Month 15]
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Progression free survival (PFS)
[Time Frame: anticipated for January 2023 (after 213 events occured and 73 months after the first patient has been randomized]
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Secondary Outcome(s)
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MRD levels in PB
[Time Frame: Month 2, 9, 13 and later time points according to the discretion of the treating physician at local laboratories]
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MRD negativity rate in PB
[Time Frame: Month 15]
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Overall response rate (ORR)
[Time Frame: Month 3, 9, 13 and 15]
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PFS
[Time Frame: anticipated for January 2023 (after 213 events occured and 73 months after the first patient has been randomized)]
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MRD levels in bone marrow (BM)
[Time Frame: at final restaging (RE): 2 month after the end of the last treatment cycle]
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Rate of complete responses (CR) / complete responses with incomplete bone marrow recovery(CRi)
[Time Frame: Interim staging (IST: cycle 4 d1), cycle 9 d1 (or final restaging (RE) for patients in the SCIT arm), IR (or three month after RE for patients in the SCIT arm respectively) and Month 15, with regard to best response achieved]
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Secondary ID(s)
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2015-004936-36
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CLL13
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Source(s) of Monetary Support
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Please refer to primary and secondary sponsors
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Results
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Results available:
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Date Posted:
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Date Completed:
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URL:
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