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Ibrutinib With Rituximab in Adults With Waldenström's Macroglobulinemia

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ClinicalTrials.gov Identifier: NCT02165397
Recruitment Status : Active, not recruiting
First Posted : June 17, 2014
Last Update Posted : December 3, 2018
Sponsor:
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Pharmacyclics LLC.

Brief Summary:
The purpose of this study is to evaluate the safety and efficacy of Ibrutinib in combination with Rituximab in subjects with Waldenström's Macroglobulinemia.

Condition or disease Intervention/treatment Phase
Waldenström's Macroglobulinemia Drug: Ibrutinib Drug: Placebo Drug: Rituximab Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 181 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: iNNOVATE Study: A Randomized, Double-Blind, Placebo- Controlled, Phase 3 Study of Ibrutinib or Placebo in Combination With Rituximab in Subjects With Waldenström's Macroglobulinemia
Actual Study Start Date : July 2014
Estimated Primary Completion Date : August 2019
Estimated Study Completion Date : August 2019


Arm Intervention/treatment
Experimental: Treatment Arm A (Ibrutinib + Rituximab)
Ibrutinib: 420 mg (3 capsules x 140 mg) orally administered daily beginning from Day 1 Rituximab: 375 mg/m2 IV per package insert weekly for four consecutive weeks, followed by a second four-weekly rituximab course after a three-month interval.
Drug: Ibrutinib
Subjects will receive 420 mg of Ibrutinib orally. Other Name: PCI-32765

Drug: Rituximab
Drug: rituximab Subjects will receive rituximab 375mg/m2 intravenously Other Name: Rituxan

Experimental: Treatment Arm B (Placebo + Rituximab)
Placebo: 3 capsules of placebo orally administered daily beginning from Day 1 Rituximab: 375 mg/m2 IV per package insert weekly for four consecutive weeks, followed by a second four-weekly rituximab course after a three-month interval.
Drug: Placebo
Subjects will receive placebo capsules orally.

Drug: Rituximab
Drug: rituximab Subjects will receive rituximab 375mg/m2 intravenously Other Name: Rituxan

Experimental: Treatment Arm C (Ibrutinib)
Ibrutinib: 420 mg (3 capsules) orally administered daily beginning from Day 1
Drug: Ibrutinib
Subjects will receive 420 mg of Ibrutinib orally. Other Name: PCI-32765




Primary Outcome Measures :
  1. Progression Free Survival [ Time Frame: Up to 3 years after last subject is randomized ]

Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: At disease progression, up to 3 years after last subject is randomized ]
  2. Hematological improvement measured by hemoglobin [ Time Frame: At disease progression, up to 3 years after last subject is randomized ]
  3. Time to next Treatment (TTnT) [ Time Frame: End-of-treatment visit, up to 3 years after last subject is randomized ]
  4. Overall Survival [ Time Frame: At disease progression, up to 3 years after last subject is randomized ]
  5. Number of participants with adverse events as a measure of safety and tolerability within each treatment arm [ Time Frame: Up to 30 days following the last dose of study drug ]


Information from the National Library of Medicine

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

Eligibility Criteria for the Randomized Study (Arm A and Arm B)

Inclusion Criteria:

  • Untreated or previously treated for Waldenström's macroglobulinemia. Previously treated subjects must have either documented disease progression or had no response (stable disease) to the most recent treatment regimen.
  • Centrally confirmed clinicopathological diagnosis of WM
  • Measurable disease defined as serum monoclonal IgM >0.5 g/dL.
  • Symptomatic disease meeting at least 1 of the recommendations from the Second International Workshop on Waldenström Macroglobulinemia for requiring treatment
  • Hematology and biochemical values within protocol-defined limits
  • Men and women ≥ 18 years of age.
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.

Exclusion Criteria:

  • Known involvement of the central nervous system by WM.
  • Disease that is refractory to the last prior rituximab-containing therapy defined as either

    • Relapse after the last rituximab-containing therapy <12 months since last dose of rituximab, OR
    • Failure to achieve at least a MR after the last rituximab-containing therapy. If the subject meets this exclusion criterion and therefore is excluded from the main randomized study, participation in the non randomized substudy (Arm C) may be considered
  • Rituximab treatment within the last 12 months before the first dose of study drug.
  • Known anaphylaxis or IgE-mediated hypersensitivity to murine proteins or to any component of rituximab.
  • Prior exposure to ibrutinib or other BTK inhibitors.
  • Known bleeding disorders (eg, von Willebrand's disease) or hemophilia.
  • History of stroke or intracranial hemorrhage within 12 months prior to enrollment.
  • Any uncontrolled active systemic infection.
  • Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk.
  • Currently active, clinically significant cardiovascular disease
  • Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor

Eligibility Criteria for Open-label Substudy Treatment Arm C

The Inclusion/Exclusion criteria for the substudy (Arm C) are identical to those described above for the randomized study but, to be eligible, subjects need to be considered refractory to the last prior rituximab-containing therapy defined as either

  • Relapse after the last rituximab-containing therapy <12 months since last dose of rituximab, OR
  • Failure to achieve at least a MR after the last rituximab-containing therapy.

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): NCT02165397


  Show 48 Study Locations
Sponsors and Collaborators
Pharmacyclics LLC.
Janssen Research & Development, LLC
Investigators
Study Director: Bernhard Hauns, MD Pharmacyclics LLC an AbbVie Company

Publications:
Responsible Party: Pharmacyclics LLC.
ClinicalTrials.gov Identifier: NCT02165397     History of Changes
Other Study ID Numbers: PCYC-1127-CA
First Posted: June 17, 2014    Key Record Dates
Last Update Posted: December 3, 2018
Last Verified: November 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Pharmacyclics LLC.:
Ibrutinib
Pharmacyclics
PCYC
Lymphoma
Btk inhibitor
WM
Rituximab
Rituxan
Waldenström's
Waldenstrom Macroglobulinemia
non-Hodgkin lymphoma
NHL

Additional relevant MeSH terms:
Waldenstrom Macroglobulinemia
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents