Phase II Trial GA101 Inbrutinib B CLL

NCT02666898 | Completed Phase 2 DMC

• 1 other identifier: ICLL07GAI
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 1

Brief Summary

Phase II study testing chemo-free induction therapy with Ibrutinib + Obinutuzumab nine months / Study Part 1: All patients will receive 8 courses of GA101 + ibrutinib 420mg PO every 28 days Study Part 2: After evaluation at D1 of month 9: If patients are in CR with BM MRD \< 10-4, they will continue ibrutinib alone at a dose of 420mg daily If patients have BM MRD \>10-4 whatever IWCLL 2008 responses or PR they will receive four courses of GA101 + FC at 28-day intervals + Ibrutinib PO until final evaluation of M16

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Keywords

Residual disease

Outcome Measures

Primary Outcomes (2)

• Study treatment response

  IWCLL criteria response

  month 16

• Study treatment response

  MRD

  month 16

Secondary Outcomes (4)

• progression free survival

  month 16

• progression free survival

  month 16

• overall survival

  month 16

• time to next treatment

  36 months

Study Arms (1)

Obinutuzumab and Ibrutinib CLL treatment

EXPERIMENTAL

3 parts PART 1: 6 cycles of GA101 + Ibrutinib 420mg PO/ 28 days: GA101: C 1 D1: 100mg, D2: 900mg D8 and D15: 1000 mg i.v C 2 to 6 :D1 1000 mg i.v Ibrutinib: D3 Month 1 to Day 30 Month 15: 420mg daily PO PART 2: 4 cycles / 28 days After evaluation at D1 month 9: * patients in CR with BM MRD \< 10-4, Ibrutinib 420mg daily * patients with BM MRD \>10-4 or PR 4 courses of GA101 + FC/ 28-day + Ibrutinib PO until M16 Cycle 1 to 4 - GA101: 1000 mg i.v on day 1 * Fludarabine : 40 mg/m² per os, days 2-4, / 28 days * Cyclophosphamide : 250 mg/m² per os, days 2-4, / 28 days * Ibrutinib 420mg/day PO PART 3 (only in GAI-FC+Ibru arm) : After evaluation at D1 of M16: * patients CR with BM MRD\< 10-4, treatment stopped * patients CR with BM MRD \>10-4, Ibrutinib continued until PD or PB MRD becomes negative.

Drug: GA101; Drug: Ibrutinib; Drug: Cyclophosphamide; Drug: Fludarabine

Interventions

GA101 DRUG

Part 1 :6 cycles Obinutuzumab/GA101: First cycle: D1: 100mg, D2: 900mg D8 and D15: 1000 mg i.v Cycle 2 to 6 (every 28 days) : D1 of every cycle: 1000 mg i.v PART 2 4 cycles -patients have BM MRD \>10-4 or PR: Cycle 1 to 4 Obitinuzumab/GA101: 1000 mg i.v on day 1

Also known as: Obinutuzumab

Obinutuzumab and Ibrutinib CLL treatment

Ibrutinib DRUG

Part 1 :6 cycles Cycle 2 to 6 (every 28 days) :Ibrutinib: D3 Month 1 to Day 30 Month 15: 420mg daily PO PART 2:4 cycles * patients in CR with BM MRD \< 10-4 : Ibrutinib alone 420mg daily * patients with BM MRD \>10-4 whatever responses or PR :Cycle 1 to 4 Ibrutinib 420mg daily with Cyclophosphamide and Fludarabine

Also known as: Imbruvica

Obinutuzumab and Ibrutinib CLL treatment

Cyclophosphamide DRUG

PART 2 : patients with BM MRD \>10-4 or PR (except PD and SD), receive : 4 cycles of FC+GA101 every 28 days Cyclophosphamide : 250 mg/m² per os, D2 to D4 in association with GA101, ibrutinib and fludarabine

Also known as: Endoxan

Obinutuzumab and Ibrutinib CLL treatment

Fludarabine DRUG

PART 2 : patients with BM MRD \>10-4 or PR (except PD and SD), receive : 4 cycles of FC+GA101 every 28 days : Fludarabine : 40 mg/m² per os, D2 to D4 in association with GA101, ibrutinib and cyclophosphamide

Also known as: Fludara

Obinutuzumab and Ibrutinib CLL treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient information and written informed consent
• Age 18 years or older
• Immunophenotypically confirmed B-CLL (IWCLL2008 and Matutes score 4 or 5)
• Patients with no prior treatment (chemotherapy, radiotherapy, immunotherapy) except steroids for less than 1 month
• Absence of 17p deletion as assessed by FISH (\< 10 % positive nuclei)
• Performance status ECOG \< 2
• Hematology values must be within the following limits:
• Absolute neutrophil count (ANC) \<1 G/L independent of growth factor support
• Platelets \<100 G/L or \<50 G/L if bone marrow involvement independent of transfusion support in either situation
• Biochemical values within the following limits:
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 x ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin
• Serum creatinine ≤ 2 x ULN or estimated Glomerular Filtration Rate (Cockroft Gault≥ 40 mL/min/1.73m2
• Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during and after the study. For females, these restrictions apply for 1 month after the last dose of study drug. For males, these restrictions apply for 3 months after the last dose of study drug.
• Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin \[Beta-hCG\]) or urine pregnancy test at Screening. Women who are pregnant or breastfeeding are ineligible for this study.

You may not qualify if:

• Binet stage A and B without active disease according to IWCLL 2008 criteria
• Known HIV seropositivity
• Hepatitis B or C seropositivity (unless clearly due to vaccination)
• Life expectancy \< 6 months
• Patient refusal to perform the bone marrow biopsy for evaluation points
• Clinically significant auto-immune anemia
• Active second malignancy currently requiring treatment (except basal cell carcinoma in situ endometrial carcinoma and incidental prostate carcinoma) and/or less than 5 years CR after breast cancer
• Any severe co-morbid conditions such as Class III or IV heart failure, myocardial infarction within months, unstable angina, ventricular tachyarrhythmias requiring ongoing treatment, severe chronic obstructive pulmonary disease with hypoxemia, uncontrolled diabetes mellitus, or uncontrolled hypertension
• Concomitant disease requiring prolonged use of corticosteroids (\> 1 month)
• Known hypersensitivity with anaphylactic reaction to humanized monoclonal antibodies or any of the study drugs
• Contraindication to the use of Obinutuzumab.
• Contraindication to use of Ibrutinib
• Transformation to aggressive B-cell malignancy (e.g. diffuse large cell lymphoma, Hodgkin lymphoma, or prolymphocytic leukaemia)
• Active bacterial, viral or fungal infection
• Abnormal renal function with creatinine clearance \< 60 ml/min calculated according to the formula of Cockcroft and Gault

Sponsors & Collaborators

• French Innovative Leukemia Organisation: lead
• Roche Pharma AG: collaborator
• Janssen-Cilag Ltd.: collaborator

Study Sites (1)

Sponsor FILO

Tours, 37054, France

Location

Related Publications (3)

• Michallet AS, Letestu R, Le Garff-Tavernier M, Campos L, Ticchioni M, Dilhuydy MS, Morisset S, Rouille V, Mahe B, Laribi K, Villemagne B, Ferrant E, Tournilhac O, Delmer A, Molina L, Leblond V, Tomowiak C, de Guibert S, Orsini-Piocelle F, Banos A, Carassou P, Cartron G, Fornecker LM, Ysebaert L, Dartigeas C, Truchan-Graczyk M, Vilque JP, Schleinitz TA, Cymbalista F, Lepretre S, Levy V, Nguyen-Khac F, Feugier P. A fixed-duration immunochemotherapy approach in CLL: 5.5-year results from the phase 2 ICLL-07 FILO trial. Blood Adv. 2023 Aug 8;7(15):3936-3945. doi: 10.1182/bloodadvances.2022009594.

  PMID: 37026799 DERIVED

• Michallet AS, Letestu R, Le Garff-Tavernier M, Aanei C, Ticchioni M, Dilhuydy MS, Subtil F, Rouille V, Mahe B, Laribi K, Villemagne B, Salles G, Tournilhac O, Delmer A, Portois C, Pegourie B, Leblond V, Tomowiak C, De Guibert S, Orsini Piocelle F, Banos A, Carassou P, Cartron G, Fornecker LM, Ysebaert L, Dartigeas C, Truchan-Graczyk M, Vilque JP, Aurran T, Cymbalista F, Lepretre S, Levy V, Nguyen-Khac F, Feugier P. A fixed-duration, measurable residual disease-guided approach in CLL: follow-up data from the phase 2 ICLL-07 FILO trial. Blood. 2021 Feb 25;137(8):1019-1023. doi: 10.1182/blood.2020008164.

  PMID: 33167024 DERIVED

• Michallet AS, Dilhuydy MS, Subtil F, Rouille V, Mahe B, Laribi K, Villemagne B, Salles G, Tournilhac O, Delmer A, Portois C, Pegourie B, Leblond V, Tomowiak C, de Guibert S, Orsini F, Banos A, Carassou P, Cartron G, Fornecker LM, Ysebaert L, Dartigeas C, Truchan Graczyk M, Vilque JP, Aurran T, Cymbalista F, Lepretre S, Levy V, Nguyen-Khac F, Le Garff-Tavernier M, Aanei C, Ticchioni M, Letestu R, Feugier P. Obinutuzumab and ibrutinib induction therapy followed by a minimal residual disease-driven strategy in patients with chronic lymphocytic leukaemia (ICLL07 FILO): a single-arm, multicentre, phase 2 trial. Lancet Haematol. 2019 Sep;6(9):e470-e479. doi: 10.1016/S2352-3026(19)30113-9. Epub 2019 Jul 16.

  PMID: 31324600 DERIVED

Related Links

• FILO internet site

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasm, Residual

Interventions

obinutuzumab; ibrutinib; Cyclophosphamide; fludarabine; fludarabine phosphate

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Valérie ROUILLE, Mrs

  French Innovative Leukemia Organisation

  STUDY DIRECTOR

• Pierre FEUGIER, MD PD

  French Innovative Leukemia Organisation

  PRINCIPAL INVESTIGATOR

• Anne Sophie MICHALLET, MD

  French Innovative Leukemia Organisation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2015
• First Posted: January 28, 2016
• Study Start: October 1, 2015
• Primary Completion: May 1, 2017
• Study Completion: September 1, 2023
• Last Updated: November 26, 2025

Record last verified: 2025-11

Locations

FR (1)