Phase II Trial GA101 Inbrutinib B CLL

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Keywords

Residual disease

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

Detailed description

Phase II study testing chemo-free induction therapy with Ibrutinib + Obinutuzumab during nine months followed by a MRD-driven strategy. Assessment of response as well as bone marrow MRD evaluation will be performed at Day 1 month 9: 1. Patients reaching CR with marrow MRD below 10-4 threshold will continue ibrutinib during 6 additional months. 2. Patients in PR or bone marrow MRD \> 10-4 will receive Ibrutinib during 6 additional months and 4 courses of FC+ GA101. At Day 1 Month 16, patients in CR but with MRD\> 10-4 will continue Ibrutinib until progressive disease. 3. Patients in stable or progressive disease will be excluded out of the trial. Final evaluation of response (with BM MRD) will be performed at Day 1 Month 16.

Anne‐Sophie Michallet, Rémi Letestu, Magali Le Garff‐Tavernier, Lydia Campos, Ticchioni Michel et al. (33 authors)

Blood Advances2023-04-077 citations

10.1182/bloodadvances.2022009594

A Fixed-Duration Immunochemotherapy Approach Combined with Ibrutinib in CLL Produces Deep and Sustained MRD Responses: 5.5-Year Results from the Icll-07 Filo Trial

Anne‐Sophie Michallet, Rémi Letestu, Magali Le Garff‐Tavernier, Carmen Aanaei, Michel Ticchioni et al. (34 authors)

Blood2022-11-15

10.1182/blood-2022-157963

A fixed-duration, measurable residual disease–guided approach in CLL: follow-up data from the phase 2 ICLL-07 FILO trial

Anne‐Sophie Michallet, Rémi Letestu, Magali Le Garff‐Tavernier, Carmen Aanei, Michel Ticchioni et al. (34 authors)

Blood2020-11-0913 citations

10.1182/blood.2020008164

Maintenance of Long-Term Undetectable Minimal Residual Disease after Combination of Ibrutinib with Abbreviated Chemotherapy in the Icll-07 Filo Trial

Anne‐Sophie Michallet, Marie‐Sarah Dilhuydy, Fabien Subtil, Valérie Rouille, Béatrice Mahé et al. (34 authors)

Blood2019-11-13

10.1182/blood-2019-126720

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.

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, Lévy V, Nguyen-Khac F, Le Garff-Tavernier M, Aanei C, Ticchioni M, Letestu R, Feugier P.

2019-07-1618 citations

10.1016/s2352-3026(19)30113-9

Interventions

DRUGGA101

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

DRUGIbrutinib

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

DRUGCyclophosphamide

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

DRUGFludarabine

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

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

* Patient information and written informed consent * Age 18 years or older * Immunophenotypically confirmed B-CLL (IWCLL2008 and Matutes score 4 or 5) * Binet stage C according to IWCLL 2008 criteria or Binet stage A and B with active disease could be considered for inclusion. * 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 * CIRS (Cumulative Illness Rating Scale) ≤ 6 (see appendix 4 for calculation of CIRS score) Mandatory inclusion criteria for treatment with ibrutinib 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. * Sign (or their legally-acceptable representatives must sign) an informed consent document indicating that they understand the purpose of and procedures required for the study, including biomarkers, and are willing to participate in the study

Exclusion criteria

* 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) * Active hemolysis (isolated positive DAT is not an

Design outcomes

Primary

Measure	Time frame	Description
Study treatment response	month 16	IWCLL criteria response

Secondary

Measure	Time frame	Description
progression free survival	month 16	relapse
overall survival	month 16	death
time to next treatment	36 months	date of new treatment after first relapse

Countries

France

Outcome results

None listed