Chronic Lymphocytic Leukemia With 17p Deletion, Small Lymphocytic Lymphoma With 17p Deletion
Conditions
Keywords
CLL, SLL
Brief summary
An Open-label, Single arm, Multicenter Phase 2 Study of the Bruton's Tyrosine Kinase Inhibitor ibrutinib in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma with 17p Deletion
Detailed description
This is a multicenter, international, open-label, single arm, Phase 2 study designed to evaluate the efficacy and safety of ibrutinib in subjects with relapsed/refractory CLL or SLL with del 17p. All subjects will receive ibrutinib until disease progression or unacceptable toxicity occurs.
Interventions
DRUGIbrutinib
All subjects will receive ibrutinib 420 mg (3 x 140-mg capsules) orally once daily.
Sponsors
Janssen Research & Development, LLC
Pharmacyclics LLC.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Documentation of del (17p13.1) * Must have relapsed or refractory CLL/SLL after receiving at least 1 prior line of systemic therapy. * Measurable nodal disease by computed tomography (CT) Key
Exclusion criteria
* History or current evidence of Richter's transformation or prolymphocytic leukemia * Prior hematologic stem cell transplantation \<6 months from study enrollment or any ongoing GVHD * Prior exposure to ibrutinib
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | The median time on study for all treated participants is 33.3 (range 0.5 - 40.1) months | The primary objective of this study is to evaluate the efficacy of ibrutinib in terms of ORR according to an Independent Review Committee (IRC). ORR based upon IRC assessment is the proportion of responders in the all treated population. Responders were subjects who achieved partial response (PR) or better, ie, complete response (CR), complete response with incomplete marrow recovery (CRi), nodule partial response (nPR) or PR, per IWCLL 2008 criteria with the clarification for treatment-related lymphocytosis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events (AEs) | From first dose of PCI-32765 to within 30 days of last dose for each participant or until study closure | Number of participants who had experienced at least one treatment emergent AE |
Countries
Australia, Belgium, Canada, Germany, New Zealand, Sweden, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
One hundred forty-five subjects were enrolled and 144 subjects received at least 1 dose of PCI-32765 and constitute the all treated population and the safety analysis set.
Participants by arm
| Arm | Count |
|---|---|
| PCI-32765 All subjects received PCI-32765 420 mg (3 x 140-mg capsules) orally once daily.
PCI-32765: All subjects received PCI-32765 420 mg (3 x 140-mg capsules) orally once daily. | 144 |
| Total | 144 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 4 |
| Overall Study | Progressive Disease | 18 |
| Overall Study | Unacceptable toxicity, AE or death | 18 |
| Overall Study | Withdrawal of consent for treatment | 3 |
Baseline characteristics
| Characteristic | PCI-32765 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 69 Participants |
| Age, Categorical Between 18 and 65 years | 75 Participants |
| Age, Continuous | 64.4 years STANDARD_DEVIATION 9.9 |
| Gender Female | 48 Participants |
| Gender Male | 96 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 144 / 144 |
| serious Total, serious adverse events | 76 / 144 |
Outcome results
Primary
Overall Response Rate
The primary objective of this study is to evaluate the efficacy of ibrutinib in terms of ORR according to an Independent Review Committee (IRC). ORR based upon IRC assessment is the proportion of responders in the all treated population. Responders were subjects who achieved partial response (PR) or better, ie, complete response (CR), complete response with incomplete marrow recovery (CRi), nodule partial response (nPR) or PR, per IWCLL 2008 criteria with the clarification for treatment-related lymphocytosis.
Time frame: The median time on study for all treated participants is 33.3 (range 0.5 - 40.1) months
Population: Efficacy analyses were performed on all 144 treated subjects. The primary analysis (PA) used IRC assessment of efficacy endpoints. In the PA, there were no differences between the IRC and investigator responses. IRC assessment was no longer performed after the PA and the final analysis result report investigator-assessed efficacy outcomes.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ibrutinib | Overall Response Rate | 77.8 % of participants with response by PI |
Secondary
Number of Participants With Treatment Emergent Adverse Events (AEs)
Number of participants who had experienced at least one treatment emergent AE
Time frame: From first dose of PCI-32765 to within 30 days of last dose for each participant or until study closure
Population: Participants who received at least 1 dose of PCI-32765 and constitute the all treated population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ibrutinib | Number of Participants With Treatment Emergent Adverse Events (AEs) | 144 participants |