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

Primary Purpose

Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Rituximab
Ibrutinib
Sponsored by
Janssen Research & Development, LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Treatment Arm A

Treatment Arm B

Arm Description

Outcomes

Primary Outcome Measures

Progression-free Survival (PFS)
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

Overall Response Rate (ORR)
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.
Overall Survival (OS)
Overall survival was defined as the interval between the date of randomization and the date of death from any cause.
Number of Participants With Sustained Hematologic Improvement
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.
Number of Participants With Clinically Relevant Shifts in Disease-Related Symptoms
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.

Full Information

First Posted
October 25, 2013
Last Updated
June 26, 2018
Sponsor
Janssen Research & Development, LLC
Collaborators
Pharmacyclics LLC.
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1. Study Identification

Unique Protocol Identification Number
NCT01973387
Brief Title
A Study of PCI-32765 (Ibrutinib) Versus Rituximab in Relapsed or Refractory Chronic Leukemia/Lymphoma
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
October 28, 2013 (Actual)
Primary Completion Date
December 1, 2015 (Actual)
Study Completion Date
August 11, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
Collaborators
Pharmacyclics LLC.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
160 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment Arm A
Arm Type
Experimental
Arm Title
Treatment Arm B
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Ibrutinib
Intervention Description
420 mg capsules administered by mouth daily until disease progression or unacceptable toxicity, whichever occurs first.
Primary Outcome Measure Information:
Title
Progression-free Survival (PFS)
Description
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.
Time Frame
From the date of randomization to the date of disease progression or death, whichever was first reported (Up to 3.7 years)
Secondary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
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.
Time Frame
From the date of randomization to disease progression (Up to 3.7 years)
Title
Overall Survival (OS)
Description
Overall survival was defined as the interval between the date of randomization and the date of death from any cause.
Time Frame
From the date of randomization to the date of death (Up to 3.7 years)
Title
Number of Participants With Sustained Hematologic Improvement
Description
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.
Time Frame
From the date of randomization to disease progression (Up to 3.7 years)
Title
Number of Participants With Clinically Relevant Shifts in Disease-Related Symptoms
Description
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.
Time Frame
From the date of randomization to disease progression (Up to 3.7 years)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
City
Concord
Country
Australia
City
Gosford
Country
Australia
City
Heidelberg
Country
Australia
City
Perth
Country
Australia
City
Tweed Heads
Country
Australia
City
Beijing
Country
China
City
Chendu
Country
China
City
Fuzhou
Country
China
City
Guangzhou
Country
China
City
Jinan
Country
China
City
Nanjing
Country
China
City
Qingdao
Country
China
City
Shanghai
Country
China
City
Suzhou
Country
China
City
Tianjin
Country
China
City
Unk Hangzhou
Country
China
City
Wuhan
Country
China
City
Xian
Country
China
City
Johor Bahru
Country
Malaysia
City
Kuala Lumpur
Country
Malaysia
City
Melaka
Country
Malaysia
City
Subang Jaya
Country
Malaysia
City
Changhua
Country
Taiwan
City
Kaohsiung
Country
Taiwan
City
Tainan
Country
Taiwan
City
Taipei
Country
Taiwan

12. IPD Sharing Statement

Learn more about this trial

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

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