Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 2 of 130 for:    Venetoclax AND Relapsed

A Prospective, Multicenter, Phase-II Trial of Ibrutinib Plus Venetoclax in Patients With Creatinine Clearance >= 30 ml/Min Who Have Relapsed or Refractory Chronic Lymphocytic Leukemia (RR-CLL) With or Without TP53 Aberrations

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: NCT03226301
Recruitment Status : Active, not recruiting
First Posted : July 21, 2017
Last Update Posted : May 14, 2019
Sponsor:
Collaborator:
Nordic CLL Study Group
Information provided by (Responsible Party):
Stichting Hemato-Oncologie voor Volwassenen Nederland

Tracking Information
First Submitted Date  ICMJE May 15, 2017
First Posted Date  ICMJE July 21, 2017
Last Update Posted Date May 14, 2019
Actual Study Start Date  ICMJE July 26, 2017
Estimated Primary Completion Date January 1, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 20, 2017)
Number of patients with progression free survival 27 months after starting treatment [ Time Frame: 27 months after last patient in trial ]
arm B of the study
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03226301 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 20, 2017)
  • Number of patients with MRD negativity 27 months after starting treatment [ Time Frame: 27 months after last patient in trial ]
    all arms of the study
  • Number of patients with progression free survival [ Time Frame: 7 years after last patient in ]
    all arms of the study
  • Number of patients reinitiating treatment [ Time Frame: 7 years after last patient in ]
    arm B of the study
  • Number of patients with treatment failure after reinitiating treatment [ Time Frame: 7 years after last patient in ]
    arm B of the study
  • Number of patients initiating new CLL treatment [ Time Frame: 7 years after last patient in ]
    all arms of the study
  • Number of patients with MRD negativity 12 (peripheral blood) and 15 months (peripheral blood and bone marrow) after starting treatment [ Time Frame: 15 months after last patient in trial ]
    all arms of the study
  • Number of patients alive [ Time Frame: 7 years after last patient in ]
    all arms of the study
  • Number of patients with complete remission, partial remission and stable disease and the duration of remission for each group [ Time Frame: 7 years after last patient in ]
    all arms of the study
  • Number and grading of adverse events, serious adverse events and adverse events of special interest (bleeding, atrial fibrillation and tumorlysis) [ Time Frame: 7 years after last patient in ]
    all arms of the study
  • Number of patients with improved quality of life (by EORTC QLQ-C30 and QLQ-CLL16 questionnaires) [ Time Frame: 51 months after last patient in trial ]
    all arms of the study
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Prospective, Multicenter, Phase-II Trial of Ibrutinib Plus Venetoclax in Patients With Creatinine Clearance >= 30 ml/Min Who Have Relapsed or Refractory Chronic Lymphocytic Leukemia (RR-CLL) With or Without TP53 Aberrations
Official Title  ICMJE A Prospective, Multicenter, Phase-II Trial of Ibrutinib Plus Venetoclax in Patients With Creatinine Clearance >= 30 ml/Min Who Have Relapsed or Refractory Chronic Lymphocytic Leukemia (RR-CLL) With or Without TP53 Aberrations
Brief Summary The aim of the current trial is to evaluate if combination treatment with venetoclax + ibrutinib in patients with relapsed or refractory chronic lymphocytic leukemia (RR CLL) can lead to MRD negativity, which may induce long lasting remissions for MRD-negative patients randomized to stopping treatment after 15 induction cycles.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
All patients receive ibrutinib + venetoclax (with delayed start and ramp up of venetoclax from cycle 3) for the 15 cycles. Patients not achieving MRD negativity after cycle 12 (PB) AND/OR cycle 15 (PB+BM) continue on ibrutinib maintenance (non-randomized group). Patients achieving MRD negativity after cycle 12 (PB) AND cycle 15 (PB+BM) are randomized 1:2 between ibrutinib maintenance (arm A) and stopping treatment (observation, arm B).
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Chronic Lymphocytic Leukemia in Relapse
  • Chronic Lymphocytic Leukemia in Remission
Intervention  ICMJE
  • Drug: Ibrutinib + Venetoclax 15 cycles
    Cycle 1 + 2: 420 mg ibrutinib, day 1-28 | Cycle 3: 420 mg ibrutinib, day 1-28 | 20 mg venetoclax, day 1-7 | 50 mg venetoclax, day 8-14 | 100 mg venetoclax, day 15-21 | 200 mg venetoclax, day 22-28 | Cycle 4-15: 420 mg ibrutinib, day 1-28 + 400mg venetoclax, day 1-28
  • Drug: Ibrutinib until progression/relapse
    420mg ibrutinib daily until progression/relapse
  • Drug: Possible reinitiation treatment: Ibrutinib + Venetoclax 12 cycles
    Cycle 1: 420 mg ibrutinib | 20 mg venetoclax, day 1-7 | 50 mg venetoclax, day 8-14 | 100 mg venetoclax, day 15-21 | 200 mg venetoclax, day 22-28 | cycles 2-12: 420 mg ibrutinib, day 1-28 + 400 mg venetoclax, day 1-28
Study Arms  ICMJE
  • Experimental: Ibrutinib until progression/relapse

    All patients receive ibrutinib + venetoclax (with delayed start and ramp up of venetoclax from cycle 3) for the 15 cycles.

    MRDpositive patients (PB and BM) will continue on Ibrutinib maintenance (non-randomized group) until progression/relapse

    Interventions:
    • Drug: Ibrutinib + Venetoclax 15 cycles
    • Drug: Ibrutinib until progression/relapse
  • Experimental: Arm A

    All patients receive ibrutinib + venetoclax (with delayed start and ramp up of venetoclax from cycle 3) for the 15 cycles.

    MRD negative patients (PB and BM) will be randomized to Arm A or Arm B. Arm A: Ibrutinib until progression/relapse (Continuous ibrutinib treatment until toxicity or progression)

    Interventions:
    • Drug: Ibrutinib + Venetoclax 15 cycles
    • Drug: Ibrutinib until progression/relapse
  • Experimental: Arm B

    All patients receive ibrutinib + venetoclax (with delayed start and ramp up of venetoclax from cycle 3) for the 15 cycles.

    MRD negative patients (PB and BM) will be randomized to Arm A or Arm B. Arm B: Observation until event.

    Patients randomized to Arm B will get reinitiation of therapy during the observation period in case of:

    • progression according to IWCLL criteria or
    • MRD≥10-3 (PB) and at least one month later MRD ≥10-2 (PB).

    Treatment reinitiation will consist of ibrutinib and venetoclax (with ramp up of venetoclax from cycle 1) for 12 cycles

    Interventions:
    • Drug: Ibrutinib + Venetoclax 15 cycles
    • Drug: Possible reinitiation treatment: Ibrutinib + Venetoclax 12 cycles
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: July 20, 2017)
230
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE January 1, 2026
Estimated Primary Completion Date January 1, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Documented CLL or SLL requiring treatment according to IWCLL criteria after either being refractory to first line therapy or relapse after initial therapy.

    • Age at least 18 years.
    • Adequate bone marrow function defined as:

      • Absolute neutrophil count (ANC) >0.75 x 109/L
      • Platelet count >30,000 /μL 30 x 109/L.
      • Hemoglobin >8.0 g/dL (5 mmol/L) Unless directly attributable to CLL infiltration of the bone marrow, proven by bone marrow biopsy
    • Creatinine clearance (CrCL) ≥ 30ml/min calculated according to the modified formula of Cockcroft and Gault or directly measured with 24hr urine collection.
    • Adequate liver function as indicated

      • Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 3.0 x upper limit of normal (ULN)
      • Bilirubin ≤1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of nonhepatic origin)
      • Prothrombin time (PT)/International normal ratio (INR) <1.5 x ULN and PTT (activated partial thromboplastin time [aPTT]) <1.5 x ULN (unless abnormalities are related to coagulopathy or bleeding disorder).
    • 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 dose), negative testing for hepatitis C RNA within 42 days prior to registration.
    • WHO/ECOG performance status 0-3 (appendix C), stage 3 only if attributable to CLL.
    • Negative pregnancy test at study entry (for women of childbearing potential).
    • Male and female subjects of reproductive potential must agree to use both a highly effective method of birth control (e.g. implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], complete abstinence , or sterilized partner) and a barrier method (e.g., condoms, cervical ring, sponge, etc.) during the period of therapy and for 90 days after the last dose of study drug.
    • Ability and willingness to provide written informed consent and to adhere to the study visit schedule and other protocol requirements.
    • Written informed consent.

Exclusion Criteria:

  • Any prior therapy with ibrutinib and/or venetoclax.
  • Transformation of CLL (Richter's transformation).
  • Patients with a history of confirmed progressive multifocal leukoencephalopathy (PML).
  • Malignancies other than CLL currently requiring systemic therapies or not being treated in curative intention before or showing signs of progression after curative treatment.
  • Known allergy to xanthine oxidase inhibitors and/or rasburicase.
  • Known bleeding disorders (e.g., von Willebrand's disease or hemophilia).
  • Uncontrolled or active infection.
  • Patients requiring treatment with a strong cytochrome P450 (CYP) 3A inhibitor (see appendix K). or anticoagulant therapy with warfarin or phenoprocoumon or other vitamin K antagonists. Please note: Patients being treated with NOACs can be included, but must be properly informed about the potential risk of bleeding under treatment with ibrutinib.
  • History of stroke or intracranial hemorrhage within 6 months prior to registration.
  • Major surgery within 28 days prior to registration.
  • Use of investigational agents which might interfere with the study drug within 28 days prior to registration.
  • Vaccination with live vaccines within 28 days prior to registration
  • Steroid therapy within 7 days prior to registration, with the exception of inhaled steroids for asthma, topical steroids, steroids up to 25 mg of prednisolone daily to control autoimmune phenomenon's, or replacement/stress corticosteroids.
  • Pregnant women and nursing mothers.
  • Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03226301
Other Study ID Numbers  ICMJE HO141 CLL / VIsion trial
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Stichting Hemato-Oncologie voor Volwassenen Nederland
Study Sponsor  ICMJE Stichting Hemato-Oncologie voor Volwassenen Nederland
Collaborators  ICMJE Nordic CLL Study Group
Investigators  ICMJE Not Provided
PRS Account Stichting Hemato-Oncologie voor Volwassenen Nederland
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP