Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study of PCI-32765 (Ibrutinib) Versus Rituximab in Relapsed or Refractory Chronic Leukemia/Lymphoma

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: NCT01973387
Recruitment Status : Completed
First Posted : October 31, 2013
Results First Posted : February 23, 2017
Last Update Posted : July 24, 2018
Sponsor:
Collaborator:
Pharmacyclics LLC.
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
The purpose of this study is to evaluate the efficacy and safety of ibrutinib versus rituximab in adult Asia Pacific region patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Drug: Rituximab Drug: Ibrutinib Phase 3

Detailed Description:
This is a randomized (individuals assigned to study treatment by chance), open-label (identity of assigned study drug will be known) study designed to evaluate the efficacy and safety of ibrutinib versus rituximab in adult Asia Pacific region patients with relapsed/refractory CLL or SLL with active disease requiring treatment who have failed at least 1 prior line of therapy and are not considered appropriate candidates for treatment or retreatment with purine analog-based therapy. Approximately 150 patients will be randomly assigned in a 1:2 ratio into 2 treatment arms to receive either intravenous rituximab (Treatment Arm A) for 6 cycles or oral ibrutinib (Treatment Arm B) until disease progression or unacceptable toxicity, whichever occurs first. The study will include screening, treatment, and follow-up phases. Treatment will extend from randomization until study drug discontinuation. Follow-up will consist of 2 phases: post-treatment (from the discontinuation of treatment for reasons other than disease progression until the patient has progressive disease) and post-disease progression (subsequent anticancer therapy and survival status will be recorded until death, lost to follow-up, consent withdrawal, or study closure). Patients in the rituximab arm with disease progression or who meet the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria for requiring subsequent anti-CLL therapy may be considered for cross over to receive ibrutinib 420 mg orally, daily until disease progression, unacceptable toxicity, withdrawal from study, or until study end whichever occurs earliest. Efficacy evaluations will assess for disease response and progression in accordance with International Workshop on Chronic Lymphocytic Leukemia 2008 criteria. Serial pharmacokinetic (study of what a drug does to the body) blood samples will be collected in the ibrutinib treatment group. Safety will be assessed throughout the study.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Multicenter, Open-Label, Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor PCI-32765 (Ibrutinib) Versus Rituximab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Actual Study Start Date : October 28, 2013
Actual Primary Completion Date : December 1, 2015
Actual Study Completion Date : August 11, 2017


Arm Intervention/treatment
Experimental: Treatment Arm A Drug: Rituximab
Up to 6 cycles (total of 8 doses administered by intravenous infusion): 375 mg/m2 on Day 1 of Cycle 1, 500 mg/m2 on Day 15 of Cycle 1 (Weeks 1-4); 500 mg/m2 on Day 1 and Day 15 of Cycle 2 (Weeks 5-8); and 500 mg/m2 on Day 1 of Cycles 3-6 (Weeks 9-24).

Experimental: Treatment Arm B Drug: Ibrutinib
420 mg capsules administered by mouth daily until disease progression or unacceptable toxicity, whichever occurs first.




Primary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: From the date of randomization to the date of disease progression or death, whichever was first reported (Up to 3.7 years) ]
    Progression-free survival was defined as the interval between the date of randomization and the date of disease progression or death, whichever was first reported. International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria for progressive disease (PD): New enlarged nodes greater than (>)1.5 centimeter (cm), new hepatomegaly or splenomegaly, or other organ infiltrates; greater than or equal to (>=)50 percent (%) increase from nadir in existing lymph node or >=50% increase from nadir in sum of product of diameters of multiple nodes; >=50% increase from nadir in enlargement of liver or spleen; >=50% increase from baseline in lymphocyte count (and to >=5*10^9/L) unless considered treatment-related lymphocytosis; New cytopenia (Hemoglobin b [Hgb] or platelets) attributable to chronic lymphocytic leukemia (CLL) and transformation to a more aggressive histology.


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: From the date of randomization to disease progression (Up to 3.7 years) ]
    ORR defined as number of participants achieving a complete response (CR), complete response with incomplete marrow recovery (CRi), nodular partial response (nPR) or partial response (PR). IWCLL 2008 criteria: CR- No lymphadenopathy and hepatosplenomegaly, no constitutional symptoms, neutrophils >1.5*10^9/liter (L), platelets >100*10^9/L, Hgb >11 gram per deciliter (g/dL) and absolute lymphocyte count <4000/microliter (mcL); CRi- CR with incomplete recovery of bone marrow; nPR- participants meet criteria for CR, but the bone marrow biopsy shows B-lymphoid nodules, may represent a clonal infiltrate; PR- >=50% drop in lymphocyte count from baseline or <=4.0*10^9/L with following: >=50% decrease in sum products of up to 6 lymph nodes, no new enlarged lymph nodes, When abnormal, >=50% decrease in enlargement of spleen from baseline or normalization and a response in 1 of following: Neutrophils >1.5*10^9/L, Platelets>100000/mcL and Hgb>11 g/dL or >=50% improvement over baseline in all.

  2. Overall Survival (OS) [ Time Frame: From the date of randomization to the date of death (Up to 3.7 years) ]
    Overall survival was defined as the interval between the date of randomization and the date of death from any cause.

  3. Number of Participants With Sustained Hematologic Improvement [ Time Frame: From the date of randomization to disease progression (Up to 3.7 years) ]
    Sustained hematologic improvement was defined as hematological improvement that was sustained continuously for greater than or equal to (>=) 56 days without blood transfusion or growth factors: 1) Platelet counts greater than (>)100* 109/liter (L) if baseline less than or equal to (<=) 100*109/L or increase >= 50 percent (%) over baseline; 2) Hemoglobin >11 gram per deciliters (g/dL) if baseline <= 11 g/dL or increase >= 2 g/dL over baseline.

  4. Number of Participants With Clinically Relevant Shifts in Disease-Related Symptoms [ Time Frame: From the date of randomization to disease progression (Up to 3.7 years) ]
    The most common disease-related symptoms associated with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (fatigue, weight loss, fevers, night sweats, and abdominal discomfort/splenomegaly) were reported by grade.



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:

  • Eastern Cooperative Oncology Group performance status of 0-1
  • Diagnosis of chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL) that meets protocol-defined criteria
  • Laboratory values within protocol-defined parameters
  • Active disease meeting International Workshop on Chronic Lymphocytic Leukemia 2008 criteria
  • Received at least 1 prior therapy for CLL/SLL and not appropriate for treatment or retreatment with purine analog-based therapy
  • Measurable nodal disease by computed tomography
  • Female subjects of childbearing potential must have a negative serum or urine pregnancy test at Screening and agree to use highly effective methods of contraception during the study and for 90 days following the last dose with ibrutinib or 12 months following the last dose of rituximab

Exclusion Criteria:

  • Central nervous system lymphoma or leukemia
  • Prolymphocytic leukemia or history of or currently suspected Richter's transformation
  • Refractory to prior rituximab-based therapy
  • Received any chemotherapy, external beam radiation therapy, anticancer antibodies, or investigational drug within 30 days prior to first dose of study drug
  • Corticosteroid use >20 mg within 1 week prior to first dose of study drug
  • Radio- or toxin-conjugated antibody therapy within 10 weeks prior to first dose of study drug
  • Prior autologous transplant within 6 months prior to first dose of study drug
  • Prior allogeneic stem cell transplant
  • Major surgery within 4 weeks prior to first dose of study drug
  • History of prior malignancy according to protocol-defined criteria
  • Currently active clinically significant cardiovascular disease within 6 months prior to first dose with study drug
  • Uncontrolled active systemic fungal, bacterial, viral, or other ongoing anti-infective treatment administered intravenously
  • History of human immunodeficiency virus or active infection with hepatitis B or C
  • History of stroke or intracranial hemorrhage within 6 months prior to random assignment
  • Pregnant or lactating women
  • Current life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, or put the study at risk
  • Requires or receiving anticoagulation with warfarin or equivalent Vitamin K antagonists
  • Requires treatment with a strong CYP3A4/5 inhibitor
  • Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP), defined as declining hemoglobin or platelet count secondary to autoimmune destruction within the screening period or requirement for high doses of steroids (greater than [>]20 milligram [mg] daily of prednisone daily or equivalent)

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): NCT01973387


Locations
Layout table for location information
Australia
Concord, Australia
Gosford, Australia
Heidelberg, Australia
Perth, Australia
Tweed Heads, Australia
China
Beijing, China
Chendu, China
Fuzhou, China
Guangzhou, China
Jinan, China
Nanjing, China
Qingdao, China
Shanghai, China
Suzhou, China
Tianjin, China
Unk Hangzhou, China
Wuhan, China
Xian, China
Malaysia
Johor Bahru, Malaysia
Kuala Lumpur, Malaysia
Melaka, Malaysia
Subang Jaya, Malaysia
Taiwan
Changhua, Taiwan
Kaohsiung, Taiwan
Tainan, Taiwan
Taipei, Taiwan
Sponsors and Collaborators
Janssen Research & Development, LLC
Pharmacyclics LLC.
Investigators
Layout table for investigator information
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Layout table for additonal information
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT01973387     History of Changes
Other Study ID Numbers: CR102604
PCI-32765CLL3002 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: October 31, 2013    Key Record Dates
Results First Posted: February 23, 2017
Last Update Posted: July 24, 2018
Last Verified: June 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Janssen Research & Development, LLC:
Chronic lymphocytic leukemia
Small lymphocytic lymphoma
Relapsed or refractory chronic lymphocytic leukemia
Relapsed or refractory small lymphocytic lymphoma
Ibrutinib
PCI-32765
Bruton's tyrosine kinase inhibitor
Rituximab
Asia Pacific region participants

Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
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
Rituximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents