A Study of Ibrutinib in Combination With Bendamustine and Rituximab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Pharmacyclics
Information provided by (Responsible Party):
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT01611090
First received: May 15, 2012
Last updated: August 27, 2014
Last verified: August 2014

May 15, 2012
August 27, 2014
September 2012
August 2015   (final data collection date for primary outcome measure)
Progression-free survival [ Time Frame: Up to 4 years after the last patient is randomized ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01611090 on ClinicalTrials.gov Archive Site
  • Number of participants with adverse events [ Time Frame: Up to 30 days following the last dose of study drug ] [ Designated as safety issue: Yes ]
  • Overall response rate [ Time Frame: At disease progression, up to 4 years after the last patient is randomized ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 4 years after the last patient is randomized ] [ Designated as safety issue: No ]
  • Rate of minimal residual disease (MRD)-negative remissions [ Time Frame: At disease progression, up to 4 years after the last patient is randomized ] [ Designated as safety issue: No ]
  • Number of participants with improvement in hematologic values [ Time Frame: At disease progression, up to 4 years after the last patient is randomized ] [ Designated as safety issue: No ]
  • Number of participants with improvement in disease-related symptoms [ Time Frame: At disease progression, up to 4 years after the last patient is randomized ] [ Designated as safety issue: No ]
  • Number of participants with improvement in patient-reported outcome scores [ Time Frame: At disease progression, up to 4 years after the last patient is randomized ] [ Designated as safety issue: No ]
  • Plasma concentrations of ibrutinib [ Time Frame: Up to Day 2, Cycle 6 ] [ Designated as safety issue: No ]
  • Plasma concentrations of bendamustine [ Time Frame: Up to Day 2, Cycle 6 ] [ Designated as safety issue: No ]
  • Plasma concentrations of rituximab [ Time Frame: Up to Day 1, Cycle 12 ] [ Designated as safety issue: No ]
  • Number of participants with biomarkers related to B-cell receptors [ Time Frame: End-of-treatment visit (up to Day 450) ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
A Study of Ibrutinib in Combination With Bendamustine and Rituximab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Randomized, Double-blind, Placebo-controlled Phase 3 Study of Ibrutinib, a Bruton's Tyrosine Kinase (BTK) Inhibitor, in Combination With Bendamustine and Rituximab (BR) in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

The purpose of this study is to examine the safety and efficacy of Ibrutinib administered in combination with bendamustine and rituximab in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

This is a randomized (patients will be assigned by chance to study treatments), double-blind (patients and study personnel will not know the identity of study treatments), placebo (an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial)-controlled study to determine the benefits and risks of combining ibrutinib with bendamustine and rituximab (BR) in patients with relapsed or refractory CLL/SLL following at least 1 line of prior systemic therapy. Approximately 580 patients will be randomized in a 1:1 ratio to either treatment arm A (placebo) or treatment arm B (ibrutinib 420 mg).

Study medication will be administered orally once daily on a continuous schedule. All patients will receive BR as the background therapy plus either ibrutinib or placebo for a maximum of 6 cycles, after which treatment with ibrutinib or placebo will continue until disease progression or unacceptable toxicity.

A treatment cycle will be defined as 28 days. The study will include a screening phase, a treatment phase, and a follow-up phase. Study end is defined as when either 80% of the patients have died or 4 years after the last patient is randomized into the study, whichever occurs first.

Patients in treatment arm A (placebo) who complete the treatment phase, with disease progression confirmed by independent review committee, may cross over to ibrutinib treatment (as in treatment arm B), at the investigators discretion and with medical monitor approval. This open-label, next-line treatment with ibrutinib will continue until disease progression, unacceptable toxicity, withdrawal from study, or until the study end, whichever occurs earlier. One interim analysis is planned for the study. Efficacy evaluations will include computed tomography scans, laboratory testing, focused physical examinations, bone marrow biopsy and aspirate, and assessment of patient-reported outcomes. In both treatment arms, samples for the development of a population-based pharmacokinetic (PK; study of what the body does to a drug) approach will be collected. Safety will be assessed throughout the study.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • Drug: Ibrutinib
    Type=exact number, unit=mg, number=420 , form=capsule, route=oral use. Capsule is taken once daily continuously.
  • Drug: Bendamustine hydrochloride
    Type=exact number, unit=mg, number=70 mg/m2, route=intravenous use. Administered intravenously on Cycle 1, Days 2-3 and Cycles 2-6, Days 1-2.
  • Drug: Rituximab
    Type=exact number, unit=mg, number=375 mg/m2 and 500 mg/m2, route=intravenous use. Administered intravenously on Cycle 1, Day 1, and Cycles 2-6, Day 1, respectively.
  • Drug: Placebo
    Form=capsule, route=oral use. Capsule is taken once daily continuously.
  • Experimental: Ibrutinib + BR
    Ibrutinib 420 mg will be administered orally once daily on a continuous schedule. All subjects will receive background therapy with bendamustine and rituximab (BR) for a maximum of 6 cycles (a cycle is defined as 28 days, with the exception of Cycle 1, which will be 29 days to allow for rituximab dosing prior to bendamustine and study medication).
    Interventions:
    • Drug: Ibrutinib
    • Drug: Bendamustine hydrochloride
    • Drug: Rituximab
  • Placebo Comparator: Placebo + BR
    Matching placebo will be administered orally once daily on a continuous schedule. All subjects will receive background therapy with BR for a maximum of 6 cycles (a cycle is defined as 28 days, with the exception of Cycle 1, which will be 29 days to allow for rituximab dosing prior to bendamustine and study medication).
    Interventions:
    • Drug: Bendamustine hydrochloride
    • Drug: Rituximab
    • Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
578
March 2018
August 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that meets protocol-defined criteria
  • Active disease meeting at least 1 of the International Workshop on Chronic Lymphocytic Leukemia 2008 criteria for requiring treatment
  • Measurable nodal disease by computed tomography
  • Relapsed or refractory CLL or SLL following at least 1 prior line of systemic therapy consisting of at least 2 cycles of a chemotherapy-containing regimen
  • Eastern Cooperative Oncology Group Performance Status score of 0 or 1
  • Hematology and biochemical values within protocol-defined limits
  • Agrees to protocol-defined use of effective contraception
  • Women of childbearing potential must have negative blood or urine pregnancy test at screening

Exclusion Criteria:

  • Recent therapeutic interventions within 3 (chemotherapy/radiotherapy) to 10 weeks (immunotherapy)
  • Prior treatment with ibrutinib or other Bruton's tyrosine kinase inhibitors or prior randomization in any other clinical study evaluating ibrutinib
  • The presence of deletion of the short arm of chromosome 17
  • Patients previously treated with a bendamustine-containing regimen who did not achieve a response or who relapsed and required treatment within 24 months of treatment with that regimen
  • Patients for whom the goal of therapy is tumor debulking prior to stem cell transplant
  • Received a hematopoietic stem cell transplant
  • Known central nervous system leukemia/lymphoma or Richter's transformation
  • Patients with uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia
  • Chronic use of corticosteroids
  • History of prior malignancy, except: malignancy treated with curative intent and with no known active disease present for >=3 years before randomization; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated cervical carcinoma in situ without evidence of disease
  • History of stroke or intracranial hemorrhage within 6 months prior to randomization; or clinically significant cardiovascular disease
  • Requires anticoagulation with warfarin or equivalent vitamin K antagonists or treatment with strong CYP3A4/5 inhibitors
  • Known history of human immunodeficiency virus or hepatitis C, or active infection with hepatitis B or C
  • Any uncontrolled active systemic infection or any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk
  • A woman who is pregnant or breast feeding, or a man who plans to father a child while enrolled in this study or within 3 months after the last dose of study drug
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Belgium,   Brazil,   Canada,   Colombia,   Czech Republic,   France,   Germany,   Greece,   Israel,   Korea, Republic of,   Mexico,   Poland,   Portugal,   Russian Federation,   Spain,   Sweden,   Turkey,   Ukraine,   United Kingdom
 
NCT01611090
CR100840, PCI-32765CLL3001, 2012-000600-15, U1111-1135-3745
Yes
Janssen Research & Development, LLC
Janssen Research & Development, LLC
Pharmacyclics
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
Janssen Research & Development, LLC
August 2014

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