320 Participants Needed

Ibrutinib + Venetoclax for Leukemia

(TAILOR Trial)

Recruiting at 77 trial locations
SC
Overseen ByStudy Contact
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Janssen Research & Development, LLC
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Breakthrough TherapyThis drug has been fast-tracked for approval by the FDA given its high promise

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy and safety of ibrutinib + venetoclax (I+V) and ibrutinib monotherapy regimens in which dosing of ibrutinib is either proactively reduced or reactively modified in response to adverse events (AEs).

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug combination Ibrutinib and Venetoclax for leukemia?

Research shows that the combination of Ibrutinib and Venetoclax improves outcomes in patients with chronic lymphocytic leukemia (CLL), achieving high rates of undetectable disease and potentially leading to durable treatment-free remission. This combination has also shown promising results in other conditions like mantle cell lymphoma, suggesting its effectiveness in treating certain types of leukemia.12345

Is the combination of Ibrutinib and Venetoclax generally safe for humans?

The combination of Ibrutinib and Venetoclax has shown a manageable safety profile in treating certain types of leukemia, with some patients experiencing side effects like tumor lysis syndrome (a condition where cancer cells break down rapidly) and dose-limiting toxicities. However, no new safety concerns were observed in recent studies, suggesting it is generally safe for use in humans.12367

What makes the drug combination of Ibrutinib and Venetoclax unique for treating leukemia?

The combination of Ibrutinib and Venetoclax is unique because it has shown promising results in improving outcomes for patients with chronic lymphocytic leukemia (CLL), especially those who are resistant to other treatments. This combination offers a potential new standard treatment option with a manageable safety profile, even in high-risk or relapsed cases.12358

Research Team

JR

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for adults with untreated chronic lymphocytic leukemia who are not pregnant or breastfeeding, agree to use contraception, and have a certain level of physical function (ECOG status). They must have measurable disease by CT scan. People planning pregnancy soon after the study or those with other health conditions that could interfere are excluded.

Inclusion Criteria

A participant using oral contraceptives must use an additional contraceptive method
I have a lymph node that is at least 1.5 cm big, confirmed by a CT scan.
I am active and can care for myself, with little to no assistance.
See 6 more

Exclusion Criteria

I don't have worsening anemia or low platelets due to autoimmunity, nor need high-dose steroids.
My condition has not progressed to Richter's transformation or spread to my brain.
I have a known bleeding disorder like von Willebrand's or hemophilia.
See 2 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ibrutinib and venetoclax with dosing adjustments based on cohort assignment

15 cycles (each cycle = 4 weeks)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Treatment Details

Interventions

  • Ibrutinib
  • Venetoclax
Trial Overview The study tests two treatment methods: Ibrutinib alone, and in combination with Venetoclax. It aims to see how effective they are and if adjusting Ibrutinib doses can reduce side effects while maintaining benefits.
Participant Groups
4Treatment groups
Experimental Treatment
Group I: Cohort 2b: Continuous Ibrutinib MonotherapyExperimental Treatment1 Intervention
Participants will receive ibrutinib 420 mg QD for 1 cycle (1 cycle = 28 days) followed by Ibrutinib 280 mg QD (or last tolerated dose) and continue until disease progression or unacceptable toxicity.
Group II: Cohort 2a: Continuous Ibrutinib MonotherapyExperimental Treatment1 Intervention
Participants will receive ibrutinib 420 mg QD (or last tolerated dose) until disease progression (PD) or unacceptable toxicity.
Group III: Cohort 1b: Ibrutinib Lead-in+Fixed Duration Ibrutinib+VenetoclaxExperimental Treatment2 Interventions
Participants will receive ibrutinib 420 mg capsule QD for a lead-in of 3 cycles (1 cycle = 28 days). From Cycle 4, venetoclax 400 mg tablet dose ramp-up (from 20 to 400 mg over 5 weeks) will begin and ibrutinib dose will be reduced to 280 mg and will be administered QD, venetoclax 400 mg tablets QD will be administered with ibrutinib 280 mg for 12 cycles through Cycle 15.
Group IV: Cohort 1a: Ibrutinib Lead-in+Fixed Duration Ibrutinib+VenetoclaxExperimental Treatment2 Interventions
Participants will receive ibrutinib 420 milligrams (mg) capsule every day (QD) for a lead-in of 3 cycles (1 cycle = 28 days). From Cycle 4, venetoclax 400 mg tablet dose ramp-up (from 20 to 400 mg over 5 weeks) will begin, and venetoclax 400 mg QD will be administered with ibrutinib 420 mg QD, orally for 12 cycles through Cycle 15.

Ibrutinib is already approved in European Union, United States, Canada, Japan for the following indications:

🇪🇺
Approved in European Union as Imbruvica for:
  • Chronic lymphocytic leukemia
  • Mantle cell lymphoma
  • Waldenström's macroglobulinemia
  • Marginal zone lymphoma
  • Graft-versus-host disease
🇺🇸
Approved in United States as Imbruvica for:
  • Chronic lymphocytic leukemia/small lymphocytic lymphoma
  • Mantle cell lymphoma
  • Waldenström's macroglobulinemia
  • Marginal zone lymphoma
  • Graft-versus-host disease
🇨🇦
Approved in Canada as Imbruvica for:
  • Chronic lymphocytic leukemia
  • Mantle cell lymphoma
  • Waldenström's macroglobulinemia
  • Marginal zone lymphoma
🇯🇵
Approved in Japan as Imbruvica for:
  • Chronic lymphocytic leukemia
  • Mantle cell lymphoma
  • Waldenström's macroglobulinemia

Find a Clinic Near You

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead Sponsor

Trials
1,022
Recruited
6,408,000+
Giacomo Salvadore profile image

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar profile image

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Pharmacyclics LLC.

Industry Sponsor

Trials
114
Recruited
13,800+

Dr. Maky Zanganeh

Pharmacyclics LLC.

Chief Executive Officer

Degree from Louis Pasteur University in Strasbourg, France; MBA from Schiller International University in France

Dr. Ellie Im

Pharmacyclics LLC.

Chief Medical Officer

MD from an unspecified institution

Findings from Research

In a phase 3 trial with 523 patients, the combination of ibrutinib and venetoclax significantly improved progression-free survival compared to the traditional FCR treatment, with only 12 patients experiencing disease progression or death in the ibrutinib-venetoclax group versus 75 in the FCR group.
The study also found that 65.9% of patients on ibrutinib-venetoclax achieved undetectable measurable residual disease (MRD) in bone marrow after 5 years, indicating effective disease control, although there was a higher incidence of serious cardiac adverse events in this group compared to FCR.
Chronic Lymphocytic Leukemia Therapy Guided by Measurable Residual Disease.Munir, T., Cairns, DA., Bloor, A., et al.[2023]
In a retrospective study of 22 patients with chronic lymphocytic leukaemia (CLL) who progressed on ibrutinib, the combination of ibrutinib and venetoclax resulted in a median overall survival of 47.1 months, indicating potential efficacy in this challenging patient group.
For 11 patients with double-refractory CLL, the same combination therapy led to a median overall survival of 27.0 months, suggesting that this treatment may provide a valuable option for patients who have limited alternatives after failing standard therapies.
Combined ibrutinib and venetoclax for treatment of patients with ibrutinib-resistant or double-refractory chronic lymphocytic leukaemia.Hampel, PJ., Rabe, KG., Call, TG., et al.[2022]
The combination of venetoclax with rituximab showed remarkable efficacy and a manageable safety profile in treating chronic lymphocytic leukemia (CLL), both in relapsed/refractory cases and as a first-line therapy for high-risk patients.
Similarly, the combination of ibrutinib with venetoclax also demonstrated striking efficacy, suggesting that these combinations could become new standard treatment options for CLL.
Chronic lymphocytic leukemia at ASH 2017.Wanner, D., Steurer, M.[2020]

References

Chronic Lymphocytic Leukemia Therapy Guided by Measurable Residual Disease. [2023]
Combined ibrutinib and venetoclax for treatment of patients with ibrutinib-resistant or double-refractory chronic lymphocytic leukaemia. [2022]
Chronic lymphocytic leukemia at ASH 2017. [2020]
Venetoclax consolidation in high-risk CLL treated with ibrutinib for ≥1 year achieves a high rate of undetectable MRD. [2023]
Immune recovery in patients with mantle cell lymphoma receiving long-term ibrutinib and venetoclax combination therapy. [2021]
Concurrent ibrutinib plus venetoclax in relapsed/refractory mantle cell lymphoma: the safety run-in of the phase 3 SYMPATICO study. [2021]
Pharmacokinetic and Pharmacodynamic Considerations in the Treatment of Chronic Lymphocytic Leukemia: Ibrutinib, Idelalisib, and Venetoclax. [2021]
Protocol description of the HOVON 141/VISION trial: a prospective, multicentre, randomised phase II trial of ibrutinib plus venetoclax in patients with creatinine clearance ≥30 mL/min who have relapsed or refractory chronic lymphocytic leukaemia (RR-CLL) with or without TP53 aberrations. [2021]