COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Phase II Trial GA101 Inbrutinib B CLL (ICLL07GAI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02666898
Recruitment Status : Completed
First Posted : January 28, 2016
Last Update Posted : February 15, 2019
Sponsor:
Collaborators:
Roche Pharma AG
Janssen-Cilag Ltd.
Information provided by (Responsible Party):
French Innovative Leukemia Organisation

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


Condition or disease Intervention/treatment Phase
Leukemia, Lymphocytic, Chronic, B-Cell Drug: GA101 Drug: Ibrutinib Drug: Cyclophosphamide Drug: Fludarabine Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 135 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II, Multicenter, Trial, Exploring "Chemo-free" Treatment (GA101+Ibrutinib) and MRD-driven Strategy in Previously Untreated Symptomatic B-chronic Lymphocytic Leukemia Medically Fit A Study From the Goelams/GCFLLC/MW Intergroup
Actual Study Start Date : October 2015
Actual Primary Completion Date : May 2017
Actual Study Completion Date : March 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia

Arm Intervention/treatment
Experimental: Obinutuzumab and Ibrutinib CLL treatment

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

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

Other Name: Obinutuzumab

Drug: Ibrutinib

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
Other Name: Imbruvica

Drug: Cyclophosphamide

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

Other Name: Endoxan

Drug: Fludarabine

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

Other Name: Fludara




Primary Outcome Measures :
  1. Study treatment response [ Time Frame: month 16 ]
    IWCLL criteria response

  2. Study treatment response [ Time Frame: month 16 ]
    MRD


Secondary Outcome Measures :
  1. progression free survival [ Time Frame: month 16 ]
    relapse

  2. progression free survival [ Time Frame: month 16 ]
    death

  3. overall survival [ Time Frame: month 16 ]
    death

  4. time to next treatment [ Time Frame: 36 months ]
    date of new treatment after first relapse



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 exclusion criteria)
    • 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
    • Total bilirubin, gamma glutamyltransferase or transaminase levels > 2.5 ULN.
    • Any coexisting medical or psychological condition that would preclude participation in the required study procedures
    • Patient with mental deficiency preventing proper understanding of the requirements of treatment.
    • Pregnant or breastfeeding women.
    • Adult under law-control
    • Fertile male and female patients who cannot or do not wish to use an effective method of contraception, during and for 18 months after the final treatment used for the purposes of the study.
    • No affiliate to social security

Mandatory exclusion criteria for treatment with Ibrutinib

  • Major surgery within 4 weeks of randomization.
  • Known central nervous system lymphoma.
  • History of stroke or intracranial hemorrhage within 6 months prior to randomization.
  • Requires anticoagulation with warfarin or equivalent vitamin K antagonists
  • Requires treatment with strong CYP3A inhibitors.
  • Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification.
  • Vaccinated with live, attenuated vaccines within 4 weeks of randomization.
  • Known history of human immunodeficiency virus (HIV) or active Hepatitis C Virus or active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics.
  • Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02666898


Locations
Layout table for location information
France
Sponsor FILO
Tours, France, 37054
Sponsors and Collaborators
French Innovative Leukemia Organisation
Roche Pharma AG
Janssen-Cilag Ltd.
Investigators
Layout table for investigator information
Study Director: Valérie ROUILLE, Mrs French Innovative Leukemia Organisation
Principal Investigator: Pierre FEUGIER, MD PD French Innovative Leukemia Organisation
Principal Investigator: Anne Sophie MICHALLET, MD French Innovative Leukemia Organisation
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: French Innovative Leukemia Organisation
ClinicalTrials.gov Identifier: NCT02666898    
Other Study ID Numbers: ICLL07GAI
First Posted: January 28, 2016    Key Record Dates
Last Update Posted: February 15, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Keywords provided by French Innovative Leukemia Organisation:
Residual disease
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Cyclophosphamide
Fludarabine
Obinutuzumab
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological