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Chronic Lymphocytic LeukemiaPhase 3NCT01973387

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

A Phase 3 study testing Rituximab and Ibrutinib in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Janssen Research & Development, LLC at 26 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Rituximab and Ibrutinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
160 participants
Where
26 sitesin 4 countries
Study dates
28 Oct 2013to 11 Aug 2017
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 19Show fewer
  • 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)

Trial locations and contacts

26 sites in 4 countries.

26 sites in 4 countries

China13 sites

  • Study site

    Beijing

  • Study site

    Chendu

  • Study site

    Fuzhou

  • Study site

    Guangzhou

  • Study site

    Jinan

  • Study site

    Nanjing

  • Study site

    Qingdao

  • Study site

    Shanghai

  • Study site

    Suzhou

  • Study site

    Tianjin

  • Study site

    Unk Hangzhou

  • Study site

    Wuhan

  • Study site

    Xi'an

Other trials in China

Australia5 sites

  • Study site

    Concord

  • Study site

    Gosford

  • Study site

    Heidelberg

  • Study site

    Perth

  • Study site

    Tweed Heads

Other trials in Australia

Malaysia4 sites

  • Study site

    Johor Bahru

  • Study site

    Kuala Lumpur

  • Study site

    Malacca

  • Study site

    Subang Jaya

Other trials in Malaysia

Taiwan4 sites

  • Study site

    Changhua

  • Study site

    Kaohsiung City

  • Study site

    Tainan

  • Study site

    Taipei

Other trials in Taiwan

About this study

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

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).

Read the 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.

Being tested
Rituximab, Ibrutinib
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
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell, Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RituximabDrug

    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).

  • IbrutinibDrug

    420 mg capsules administered by mouth daily until disease progression or unacceptable toxicity, whichever occurs first.

Study groups in NCT01973387
Study groupRoleWhat they receive
Treatment Arm AExperimentalNot described
Receives: Drug: Rituximab
Treatment Arm BExperimentalNot described
Receives: Drug: Ibrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: From the date of randomization to the date of disease progression or death, whichever was first reported (Up to 3.7 years)

Secondary outcomes (4)

  1. 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.

    Measured: From the date of randomization to disease progression (Up to 3.7 years)

  2. Overall Survival (OS)

    Overall survival was defined as the interval between the date of randomization and the date of death from any cause.

    Measured: From the date of randomization to the date of death (Up to 3.7 years)

  3. 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.

    Measured: From the date of randomization to disease progression (Up to 3.7 years)

  4. 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.

    Measured: From the date of randomization to disease progression (Up to 3.7 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 Oct 2013 (estimated)
  2. Study start28 Oct 2013
  3. Primary completion1 Dec 2015
  4. Study completion11 Aug 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
160 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01973387
Sponsor's protocol ID
CR102604
Other IDs
PCI-32765CLL3002
Status last verified
Jun 2018
First submitted
25 Oct 2013
Last updated
24 Jul 2018
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Rituximab and Ibrutinib in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Janssen Research & Development, LLC at 26 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in China, Australia, Malaysia, Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Feb 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01973387.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Jul 2018.

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