Chronic Lymphocytic Leukemia
Conditions
Brief summary
This is a multicenter, open-label, single-arm, expanded access treatment study designed to provide obinutuzumab to patients with previously untreated Chronic Lymphocytic Leukemia (CLL) in combination with chlorambucil and to evaluate the safety and efficacy of obinutuzumab administered in combination with chlorambucil. This study will enroll patients with previously untreated CD20-positive CLL requiring treatment according to the IWCLL guidelines (Hallek et al 2008), as assessed by the investigator.
Interventions
DRUGObinutuzumab
DRUGChlorambucil
Sponsors
Genentech, Inc.
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
* Confirmed diagnosis of CD20-positive CLL (per IWCLL guidelines, Hallek et al 2008) * Previously untreated CLL requiring treatment according to the IWCLL guidelines (Hallek et al 2008), as assessed by the investigator * Adequate baseline bone marrow function unless it due to underlying CLL disease No previous treatment for CLL by chemotherapy, radiotherapy, or immunotherapy * Patients who are not appropriate to receive more intensive chemotherapy in the judgment of the investigator * Life expectancy of \> 6 months
Exclusion criteria
* Treatment with any other investigational agent or participation in another clinical trial within 28 days prior to the start of Cycle 1 * Transformation of CLL to aggressive B-cell malignancy History of severe allergic or anaphylactic reactions to monoclonal antibody therapy * Known hypersensitivity to chlorambucil or any of its excipients * History of other malignancy that could affect compliance with the protocol or interpretation of results Known active bacterial, viral, fungal, mycobacterial, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with IV antibiotics or hospitalization (related to the completion of the course of antibiotics) within 4 weeks before the start of Cycle 1 * Major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis * Known infection with human immunodeficiency virus (HIV) or Human T-Cell Leukemia Virus 1 (HTLV-1) seropositive status * Positive hepatitis serology * Women who are pregnant or lactating * Fertile men or women of childbearing potential unless 1) surgically sterile or 2) using an adequate measure of contraception such as oral contraceptives, intrauterine device, or barrier method of contraception in conjunction with spermicidal jelly * Effective contraception is required while receiving obinutuzumab. For women, effective contraception is required to continue for \>= 12 months after the last dose of obinutuzumab. For men, effective contraception is required to continue for 6 months after the last dose of chlorambucil treatment. * Vaccination with a live vaccine a minimum of 28 days prior to the start of Cycle 1
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Received Obinutuzumab and Chlorambucil in the Study | Cycles 1 to 6 (28-day cycles) | Number of participants who received obinutuzumab and chlorambucil in the study are presented in the below table. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs), AEs of Grade 3 and Above Severity, AEs of Special Interest (AESI), AEs Leading to Obinutuzumab Discontinuation or Dose Delays, Serious Adverse Events (SAEs), and Death | Up to 28 days after the last dose of study drug (up to 7 months from Day 1) | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0 was used for grading the AEs. According to NCI CTCAE, Grade 3 = severe or medically significant but not immediately life threatening; Grade 4 = life-threatening consequences, urgent intervention indicated, and Grade 5 = death. AESIs included all tumor lysis syndrome, serious infections, serious infusion-related reactions (IRR), and hepatitis B reactivation. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect. |
| Number of Participants With Objective Response | Up to end of treatment or premature discontinuation from study (up to 7 months from Day 1) | Objective response is defined as either complete response \[CR\], complete response with incomplete recovery \[CRi\], or partial response \[PR\] as determined by the treating physician's standard practice at the end of treatment or premature discontinuation from study per the International Workshop on Chronic Lymphocytic Leukemia Criteria (iwCLL criteria). Patients who have not achieved a CR or a PR, and who have not exhibited progressive disease, will be considered to have stable disease (which is equivalent to a nonresponse). |
Countries
United States
Participant flow
Recruitment details
A total of 20 participants were enrolled at 7 study sites in the United States (U.S) between 21 August 2013 and 22 January 2014.
Pre-assignment details
Of 20 participants, one patient withdrew from the study due to neutropenia and did not receive any study drug.
Participants by arm
| Arm | Count |
|---|---|
| Obinutuzumab + Chlorambucil Obinutuzumab was administered intravenously for 6 cycles (28-day cycles) as: 100 mg on Day 1, 900 mg on Day 2, and 1000 mg on Days 8 and 15 for Cycle 1; and 1000 mg on Day 1 of Cycles 2 to 6. Chlorambucil was administered orally at a dose of 0.5 mg/kg body weight on Days 1 and 15 for Cycles 1 through 6 (28-day cycles). | 19 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 2 |
| Overall Study | Commercial availability of study drug | 17 |
| Overall Study | Neutropenia | 1 |
Baseline characteristics
| Characteristic | Obinutuzumab + Chlorambucil |
|---|---|
| Age, Continuous | 67.5 years STANDARD_DEVIATION 10.33 |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 18 / 19 |
| serious Total, serious adverse events | 2 / 19 |
Outcome results
Primary
Number of Participants Who Received Obinutuzumab and Chlorambucil in the Study
Number of participants who received obinutuzumab and chlorambucil in the study are presented in the below table.
Time frame: Cycles 1 to 6 (28-day cycles)
Population: Intent-to-Treat population: It included all enrolled participants in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Obinutuzumab | Number of Participants Who Received Obinutuzumab and Chlorambucil in the Study | 19 participants |
| Chlorambucil | Number of Participants Who Received Obinutuzumab and Chlorambucil in the Study | 19 participants |
Secondary
Number of Participants With Adverse Events (AEs), AEs of Grade 3 and Above Severity, AEs of Special Interest (AESI), AEs Leading to Obinutuzumab Discontinuation or Dose Delays, Serious Adverse Events (SAEs), and Death
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered to be related to the medicinal product. National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0 was used for grading the AEs. According to NCI CTCAE, Grade 3 = severe or medically significant but not immediately life threatening; Grade 4 = life-threatening consequences, urgent intervention indicated, and Grade 5 = death. AESIs included all tumor lysis syndrome, serious infections, serious infusion-related reactions (IRR), and hepatitis B reactivation. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or results in a congenital anomaly/birth defect.
Time frame: Up to 28 days after the last dose of study drug (up to 7 months from Day 1)
Population: Safety Population: It included all enrolled participants who received at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Obinutuzumab | Number of Participants With Adverse Events (AEs), AEs of Grade 3 and Above Severity, AEs of Special Interest (AESI), AEs Leading to Obinutuzumab Discontinuation or Dose Delays, Serious Adverse Events (SAEs), and Death | Any AEs | 19 participants |
| Obinutuzumab | Number of Participants With Adverse Events (AEs), AEs of Grade 3 and Above Severity, AEs of Special Interest (AESI), AEs Leading to Obinutuzumab Discontinuation or Dose Delays, Serious Adverse Events (SAEs), and Death | Any AEs of Grade 3 and more severity | 10 participants |
| Obinutuzumab | Number of Participants With Adverse Events (AEs), AEs of Grade 3 and Above Severity, AEs of Special Interest (AESI), AEs Leading to Obinutuzumab Discontinuation or Dose Delays, Serious Adverse Events (SAEs), and Death | AEs leading to obinutuzumab discont. or delay | 8 participants |
| Obinutuzumab | Number of Participants With Adverse Events (AEs), AEs of Grade 3 and Above Severity, AEs of Special Interest (AESI), AEs Leading to Obinutuzumab Discontinuation or Dose Delays, Serious Adverse Events (SAEs), and Death | AESI | 1 participants |
| Obinutuzumab | Number of Participants With Adverse Events (AEs), AEs of Grade 3 and Above Severity, AEs of Special Interest (AESI), AEs Leading to Obinutuzumab Discontinuation or Dose Delays, Serious Adverse Events (SAEs), and Death | Any SAEs | 2 participants |
| Obinutuzumab | Number of Participants With Adverse Events (AEs), AEs of Grade 3 and Above Severity, AEs of Special Interest (AESI), AEs Leading to Obinutuzumab Discontinuation or Dose Delays, Serious Adverse Events (SAEs), and Death | Death | 0 participants |
Secondary
Number of Participants With Objective Response
Objective response is defined as either complete response \[CR\], complete response with incomplete recovery \[CRi\], or partial response \[PR\] as determined by the treating physician's standard practice at the end of treatment or premature discontinuation from study per the International Workshop on Chronic Lymphocytic Leukemia Criteria (iwCLL criteria). Patients who have not achieved a CR or a PR, and who have not exhibited progressive disease, will be considered to have stable disease (which is equivalent to a nonresponse).
Time frame: Up to end of treatment or premature discontinuation from study (up to 7 months from Day 1)
Population: Efficacy evaluable population: It included participants who received at least one dose of study drug and had measurable disease at baseline and at least one post-baseline tumor assessment or who died within 28 days after the last dose of the study drug
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Obinutuzumab | Number of Participants With Objective Response | 4 participants |