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Open-label Extension Study in Patients 65 Years or Older With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

Phase 3
Completed
Conditions
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Interventions
Registration Number
NCT01724346
Lead Sponsor
Pharmacyclics LLC.
Brief Summary

An Open-label Extension Study in Patients 65 Years or Older with Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Who Participated in Study PCYC-1115-CA (Ibrutinib versus Chlorambucil)

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
232
Inclusion Criteria
  1. Randomized in the parent study, PCYC-1115-CA
  2. Informed consent for Study PCYC-1116-CA
  3. IRC-confirmed PD in the parent study PCYC-1115-CA or closure of the parent study
Exclusion Criteria
  1. Disease progression involving the central nervous system (CNS) or transformation to another histology
  2. Intervening chemotherapy, immunotherapy, or investigational agent specifically to treat CLL if administered before date of IRC confirmed progressive disease
  3. In the 4 weeks before dosing: radiation therapy, major surgery, or receipt of an investigational drug
  4. Requirement for treatment with a strong CYP3A inhibitor
  5. Uncontrolled systemic infection or requirement for IV antibiotics
  6. Noncompliance on the parent study(PCYC-1115-CA)

Study & Design

Study Type
INTERVENTIONAL
Study Design
CROSSOVER
Arm && Interventions
GroupInterventionDescription
ChlorambucilIbrutinibParticipants who received chlorambucil 0.5 mg/kg (to maximum 0.8 mg/kg) Days 1 and 15 of 28-day cycle up to 12 cycles in Study 1115. In Study 1116, participants had the option to crossover to next-line ibrutinib 420 mg/day after disease progression (PD).
IbrutinibNext-line ibrutinibParticipants who received ibrutinib 420 mg daily in Study 1115 received ibrutinib orally once daily. Participants continuing in first-line ibrutinib therapy entered Study 1116 at the ibrutinib dose tolerated in Study 1115.
Primary Outcome Measures
NameTimeMethod
Progression Free Survival (PFS) Based on Investigator AssessmentMedian overall follow-up of 82.7 months

PFS is defined as the time from the date of randomization to the date of disease progression determined by the investigator or date of death from any cause, whichever occurs first, regardless of the use of subsequent antineoplastic therapy prior to disease progression (PD) or death. Estimated by Kaplan-Meier method.

Secondary Outcome Measures
NameTimeMethod
Progression Free Survival After Initiation of Subsequent Anticancer Therapy (PFS2)Median overall follow-up of 82.7 months

PFS2 is defined as the time from the date of randomization to the earliest occurrence of the following three types of events:

* PD per investigator response assessment after initiation of the first subsequent anti-cancer therapy

* Initiation of second subsequent anti-cancer therapy

* Death due to any cause, regardless of administration of subsequent anticancer therapy.

Kaplan-Meier landmark estimate of the PFS2 rate at 60 months (that is, the estimated percentage of participants with PFS2 at Month 60) is presented.

Overall Survival (OS)Median overall follow-up of 82.7 months

OS is defined as the time from randomization to death due to any cause. Kaplan-Meier landmark estimate of the OS rate at 60 months (that is, the estimated percentage of participants with OS at Month 60) is presented.

Time to Next Treatment (TTNT)Median overall follow-up of 82.7 months

Time from randomization to initiation of any subsequent treatment for chronic lymphocytic leukemia (CLL).

Overall Response Rate (ORR)Median overall follow-up of 82.7 months

ORR is defined as the percentage of participants who achieve complete response (CR), complete response with an incomplete marrow recovery (CRi), nodular partial response (nPR), or partial response (PR), as determined by the investigator at or prior to initiation of subsequent antineoplastic therapy according to the International Workshop on CLL (iwCLL) 2008 criteria with the 2012 iwCLL modification stating that treatment-related lymphocytosis in the setting of improvement in other parameters was not considered as PD and the 2013 iwCLL clarification of criteria for a partial response to therapy.

Rate of Minimal Residual Disease (MRD) NegativityMedian overall follow-up of 82.7 months

Percentage of participants who achieved MRD-negative response defined as \< 1 CLL cell per 10,000 leukocytes as assessed by flow cytometry of a bone marrow aspirate and/or peripheral blood sample per central laboratory at or prior to initiation of subsequent antineoplastic therapy.

Duration of Response (DOR)Median overall follow-up of 82.7 months

DOR will be calculated for the participants achieving a protocol-defined response (Halleck 2008; CR, CRi, nPR, PR) per investigator assessment and is defined as time from the date of initial response including PR with lymphocytosis to the date of disease progression or the date of death from any cause, whichever occurs first.

Trial Locations

Locations (88)

City of Hope /ID# 1116-0047

🇺🇸

Duarte, California, United States

Moores Cancer Center at UC San Diego /ID# 1116-0408

🇺🇸

La Jolla, California, United States

Stanford University/Stanford Cancer Center, Campus Drive /ID# 1116-0038

🇺🇸

Stanford, California, United States

University of Chicago /ID# 1116-0126

🇺🇸

Chicago, Illinois, United States

Norton Cancer Institute - St Matthews /ID# 1116-0071

🇺🇸

Louisville, Kentucky, United States

Comprehensive Cancer Centers of Nevada /ID# 1116-0712

🇺🇸

Henderson, Louisiana, United States

University of Massachusetts - Worcester /ID# 1116-0307

🇺🇸

Worcester, Massachusetts, United States

Washington University-School of Medicine /ID# 1116-0221

🇺🇸

Saint Louis, Missouri, United States

Northwell Health/Long Island Jewish Hospital /ID# 1116-0350

🇺🇸

New Hyde Park, New York, United States

University of Rochester Medical Center /ID# 1116-0127

🇺🇸

Rochester, New York, United States

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City of Hope /ID# 1116-0047
🇺🇸Duarte, California, United States

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