TriangleNCT01010061 · CITED IN SOURCE DOCUMENTS
CLL11: A Study of Obinutuzumab (RO5072759 [GA101]) With Chlorambucil in Patients With Previously Untreated Chronic Lymphocytic Leukemia (Stage 1a)
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- COMPLETED
- Registry last update
- 2018-09-14
This open-label, randomized, 3-arm study will evaluate the efficacy and safety of obinutuzumab (RO5072759) in combination with chlorambucil as compared to rituximab plus chlorambucil or chlorambucil alone in patients with previously untreated chronic lymphocytic leukemia (CLL). Patients will be randomized 2:2:1 to receive a maximum of six 28-day cycles of either RO5072759 (1000 mg intravenous (iv) infusion, on days 1, 8 and 15 of cycle 1 and day 1 of cycles 2-6) plus chlorambucil (0.5 mg/kg orally, days 1 and 15 of cycles 1-6), or rituximab (iv infusion day 1, 375 mg/m\^2 cycle 1, 500 mg/m\^2 cycles 2-6) plus chlorambucil, or chlorambucil alone. Anticipated time on study treatment is \>6 months and follow-up for disease-progression and safety will be at least 5 years. In the US, this trial is sponsored/managed by Genentech.
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Progression-free Survival (PFS)
Percentage of Participants With Progression Free Survival Events
Progression Free Survival Based on Independent Review Committee (IRC) Data
Percentage of Participants With Progression Free Survival Events Based on Independent Review Committee (IRC) Data
Percentage of Participants With End of Treatment Response (EOTR)
Percentage of Participants With Best Overall Response
Event Free Survival
Overall Survival
Duration of Response
Percentage of Participants With Molecular Remission at the End of Treatment
Time to Re-Treatment/New-antileukemic Therapy
Pharmacokinetics of Obinutuzumab (RO5072759) in Combination With Chlorambucil (Clb)
European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire Score
European Organization for Research and Treatment of Cancer (EORTC) QLQ-CLL16 Questionnaire Score
Adverse events
Limitations, agreements, and source contact
Who could take part
- eligibility Criteria
- Inclusion Criteria: * Adults \>/=18 years * Documented Cluster of Differentiation Antigen 20 (CD20) + B-Cell Chronic Lymphocytic Lymphoma (B-CLL) * Previously untreated Chronic Lymphocytic Leukemia (CLL) requiring treatment according to the National Cancer Institute (NCI) criteria * Total Cumulative Illness Rating Scale (CIRS) \> 6 and/or creatinine clearance \< 70 ml/min Exclusion Criteria: * Prior CLL therapy * Transformation of CLL to aggressive Non-Hodgkin's Lymphoma (NHL) (Richter's transformation) * History of other malignancy unless the malignancy has been in remission without treatment for \>/=2 years prior to enrolment, and except for carcinoma in situ of the cervix, basal or squamous cell skin cancer, surgically treated low-grade prostate cancer, or ductal carcinoma in situ (DCIS) of the breast treated with lymphectomy alone * Positive hepatitis serology (HBV, HCV) or positive HIV or Human T Cell Leukemia Virus (HTLV) testing * Patients with active infection requiring systemic treatment
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- description
- Participants received 1000 mg obinutuzumab intravenous (IV) infusion, on Days 1 \[first infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment\], 8 and 15 in Cycle 1 and Day 1 in Cycles 2-6 (28-day cycles) plus chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles).
- intervention Names
- Drug: obinutuzumab
- Drug: chlorambucil
- label
- obinutuzumab + chlorambucil (GClb)
- type
- EXPERIMENTAL
- description
- Participants received 375 mg/m\^2 rituximab IV infusion on Day 1 of Cycle 1 then 500 mg/m\^2 IV infusions on Day 1 of Cycles 2-6 (28-day cycles) plus chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 cycles).
- intervention Names
- Drug: rituximab
- Drug: chlorambucil
- label
- rituximab + chlorambucil (RClb)
- type
- ACTIVE_COMPARATOR
- description
- Participants received chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle (6 Cycles). Participants with Progressive Disease or within 6 months of follow-up were allowed to cross over to receive obinutuzumab + chlorambucil.
- intervention Names
- Drug: chlorambucil
- label
- Chlorambucil (Clb)
- type
- ACTIVE_COMPARATOR
- interventions
- arm Group Labels
- obinutuzumab + chlorambucil (GClb)
- description
- 1000 mg obinutuzumab intravenous (IV) infusion, on Days 1 \[first infusion split 100 mg on Day 1 and 900 mg on Day 2 as per protocol amendment\], 8 and 15 in Cycle 1 and Day 1 in Cycles 2-6 (28-day cycles).
- name
- obinutuzumab
- other Names
- RO5072759
- GA101
- GAZYVA®
- type
- DRUG
- arm Group Labels
- rituximab + chlorambucil (RClb)
- description
- 375 mg/m\^2 rituximab intravenous (IV) infusion on Day 1 of Cycle 1 (Cycle duration is 28 days) then 500 mg/m\^2 IV infusions on Day 1 of Cycles 2-6.
- name
- rituximab
- other Names
- Rituxan®
- MabThera®
- type
- DRUG
- arm Group Labels
- Chlorambucil (Clb)
- obinutuzumab + chlorambucil (GClb)
- rituximab + chlorambucil (RClb)
- description
- Chlorambucil 0.5 mg/kg orally on Day 1 and 15 of each 28-day cycle.
- name
- chlorambucil
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 787
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- PFS was defined as the time from randomization to the first occurrence of progression, relapse, or death from any cause as assessed by the investigator. Progressive disease (PD) required at least one of the following: ≥50% increase in the absolute number of lymphocytes, appearance of new palpable lymph nodes (\>15 mm in longest diameter) or any new extra nodal lesion, ≥50% increase in the longest diameter of any previous site of clinically significant lymphadenopathy, ≥50% increase in the enlargement of the liver and/or spleen, Transformation to a more aggressive histology or After treatment, the progression of any cytopenia (a decrease of hemoglobin levels \>20 g/L or \<10 g/dL or a decrease of platelet counts \>50% or \<100 x 10\^9/L or by a decrease of neutrophil counts \>50% or \<1.0 x 10\^9/L).
- measure
- Progression-free Survival (PFS)
- time Frame
- Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
- description
- Percentage of Participants with Progression Free Survival Events: disease progression, relapse, or death.
- measure
- Percentage of Participants With Progression Free Survival Events
- time Frame
- Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
- secondary Outcomes
- description
- PFS was defined as the time from randomization to the first occurrence of progression, relapse, or death from any cause as assessed by Independent Review Committee. Progressive disease required at least one of the following: ≥50% increase in the absolute number of lymphocytes, appearance of new palpable lymph nodes (\>15 mm in longest diameter) or any new extra nodal lesion, ≥50% increase in the longest diameter of any previous site of clinically significant lymphadenopathy, ≥50% increase in the enlargement of the liver and/or spleen, Transformation to a more aggressive histology or After treatment, the progression of any cytopenia (a decrease of hemoglobin levels \>20 g/L or \<10 g/dL or a decrease of platelet counts \>50% or \<100 x 10\^9/L or by a decrease of neutrophil counts \>50% or \<1.0 x 10\^9/L).
- measure
- Progression Free Survival Based on Independent Review Committee (IRC) Data
- time Frame
- Randomization to clinical cutoff date of 9 May 2013 (median observation 22.8 months)
- description
- Percentage of Participants with Progression Free Survival Events: progression, relapse, or death from any cause as assessed by an Independent Review Committee.
- measure
- Percentage of Participants With Progression Free Survival Events Based on Independent Review Committee (IRC) Data
- time Frame
- Randomization to clinical cutoff date of 9 May 2013 (median observation 22.8 months)
- description
- EOTR was the first response assessment 56 days from the last dose according to the International Workshop on Chronic Lymphocytic Leukaemia (IWCLL) guidelines. CR required: Peripheral blood lymphocytes below 4 x 10\^9/L, Absence of significant lymphadenopathy, No hepatomegaly, No splenomegaly, Absence of disease, Blood counts above the following values (Neutrophils \>1.5 x 10\^9/L, Platelets \>100 x 10\^9/L, Hemoglobin \>11g/dL) and Bone marrow at least normocellular for age. CRi was CR with incomplete bone marrow recovery. PR required the following for at least 2 months from end of treatment: ≥50% decrease in peripheral blood lymphocyte count from the pre-treatment value AND Either a ≥ 50% reduction in lymphadenopathy OR ≥50% reduction of liver enlargement OR ≥50% reduction of spleen enlargement PLUS at least one of the following: Neutrophils \>1.5 x 10\^9/ or ≥50% increase, Platelets \>100 x 10\^9/L or ≥50% increase, Hemoglobin 11 g/dL or ≥50% increase.
- measure
- Percentage of Participants With End of Treatment Response (EOTR)
- time Frame
- Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
- description
- Best overall response according to IWCLL guidelines was defined as the percentage of patients with CR, CRi,PR or nPR. CR required all of the following: Peripheral blood lymphocytes below 4 x 10\^9/L, Absence of significant lymphadenopathy, No hepatomegaly, No splenomegaly, Absence of disease, Blood counts above the following values (Neutrophils \>1.5 x 10\^9/L, Platelets \>100 x 10\^9/L, Hemoglobin \>11g/dL) and Bone marrow at least normocellular for age. CRi was CR with incomplete bone marrow recovery. PR required the following for at least 2 months from end of treatment: ≥50% decrease in peripheral blood lymphocyte count from the pre-treatment value AND Either a ≥ 50% reduction in lymphadenopathy OR ≥50% reduction of liver enlargement OR ≥50% reduction of spleen enlargement PLUS at least one of the following: Neutrophils \>1.5 x 10\^9/ or ≥50% increase, Platelets \>100 x 10\^9/L or ≥50% increase, Hemoglobin 11 g/dL or ≥50% increase.
- measure
- Percentage of Participants With Best Overall Response
- time Frame
- Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
- description
- Event-free survival (EFS) was defined as the time between date of randomization and the date of disease progression/relapse, death, or start of a new anti-leukemic therapy. Progressive disease as per IWCLL criteria required at least one of the following: ≥50% increase in the absolute number of lymphocytes, appearance of new palpable lymph nodes (\>15 mm in longest diameter) or any new extra nodal lesion, ≥50% increase in the longest diameter of any previous site of clinically significant lymphadenopathy, ≥50% increase in the enlargement of the liver and/or spleen, Transformation to a more aggressive histology or After treatment, the progression of any cytopenia (a decrease of hemoglobin levels \>20 g/L or \<10 g/dL or a decrease of platelet counts \>50% or \<100 x 10\^9/L or by a decrease of neutrophil counts \>50% or \<1.0 x 10\^9/L).
- measure
- Event Free Survival
- time Frame
- Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
- description
- Overall Survival (OS) was defined as the time between the date of randomization and the date of death due to any cause.
- measure
- Overall Survival
- time Frame
- Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
- description
- Duration of Response was defined as the date the response \[either Complete Response (CR) or Partial Response (PR)\] was first recorded until the date of Disease Progression or death due to any cause. Response was assessed according IWCLL guidelines.
- measure
- Duration of Response
- time Frame
- Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
- description
- Molecular remission was defined as a minimal residual disease (MRD)-negative result at the end of treatment (assessment that occurred between 56 days and 6 months of last treatment). Molecular remission was assessed for all patients using a blood sample. Additionally, a bone marrow sample was obtained from patients whom the investigator assumed to have a complete response, consistent with the IWCLL guidelines. A combined analysis of blood and bone marrow results was conducted. A patient was considered MRD negative if result was less than 1 chronic lymphocytic leukemia (CLL) cell in 10000 leukocytes (MRD value \< 0.0001) based on the method of allele specific polymerase chain reaction (ASO-PCR).
- measure
- Percentage of Participants With Molecular Remission at the End of Treatment
- time Frame
- Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
- description
- Time to re-treatment/new anti-leukemic therapy was defined as time between the date of randomization and the date of first intake of re-treatment or new anti-leukemic therapy.
- measure
- Time to Re-Treatment/New-antileukemic Therapy
- time Frame
- Randomization to clinical cutoff date of 10 Oct 2017 (median observation 62.5 months from randomization)
- description
- Blood samples were collected from all patients allocated to the GClb treatment arm pre- and post-dose Day 1 of Cycles 1 to 6 and were sent to a laboratory. The concentration of obinutzumab in serum was determined using a validated enzyme-linked immunosorbent assay (ELISA) and was reported in micrograms/milliliter (μg/mL).
- measure
- Pharmacokinetics of Obinutuzumab (RO5072759) in Combination With Chlorambucil (Clb)
- time Frame
- Pre- and post-dose sampling on day 1 of cycles 1-6 (Up to 26.8 months)
- description
- The EORTC Quality of Life Questionnaire QLQ-C30 was used to assess patient-reported outcomes (PRO) and symptom burden. The QLQ-C30 contains 30 items including the functional scales of physical functioning (5 items), role functioning (2 items), emotional functioning (4 items), cognitive functioning (2 items), social functioning (2 items) and symptom scales including fatigue (3 items), nausea and vomiting (2 items), and pain (4 items) and six single item scales on dyspnea, sleep disturbance, appetite loss, constipation, diarrhea and financial impact. Final scores are transformed such that they range from 0 - 100, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 5 - 10 points considered to be of minimally important difference to participants. A positive change from Baseline indicated improvement.
- measure
- European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 Questionnaire Score
- time Frame
- Baseline and Cycle 4 Day 1 (Cy4D1)
- description
- EORTC Quality of Life Questionnaire (QLQ-CLL16) module was used to assess patient-reported outcomes and symptom burden. The QLQ-CLL16 module includes three multi-item scales assessing fatigue (2 items), treatment side effects and disease symptoms (8 items), infection (4 items) and two single item scales on social activities and future health worries. Final scores are transformed such that they range from 0 - 100, whereby higher scores indicate greater functioning, greater quality of life, or a greater degree of symptoms, with changes of 5 - 10 points considered to be of minimally important difference to participants. A positive change from Baseline indicated improvement.
- measure
- European Organization for Research and Treatment of Cancer (EORTC) QLQ-CLL16 Questionnaire Score
- time Frame
- Baseline and Cycle 4 Day 1 (Cy4D1)
Full study description
- brief Summary
- This open-label, randomized, 3-arm study will evaluate the efficacy and safety of obinutuzumab (RO5072759) in combination with chlorambucil as compared to rituximab plus chlorambucil or chlorambucil alone in patients with previously untreated chronic lymphocytic leukemia (CLL). Patients will be randomized 2:2:1 to receive a maximum of six 28-day cycles of either RO5072759 (1000 mg intravenous (iv) infusion, on days 1, 8 and 15 of cycle 1 and day 1 of cycles 2-6) plus chlorambucil (0.5 mg/kg orally, days 1 and 15 of cycles 1-6), or rituximab (iv infusion day 1, 375 mg/m\^2 cycle 1, 500 mg/m\^2 cycles 2-6) plus chlorambucil, or chlorambucil alone. Anticipated time on study treatment is \>6 months and follow-up for disease-progression and safety will be at least 5 years. In the US, this trial is sponsored/managed by Genentech.
- detailed Description
- Protocol BO21004 is divided into 3 separate Unique Protocol IDs for reporting results on clinicaltrials.gov because there are 3 separate primary analyses conducted at different time-points. * BO21004 (Stage 1a) \[NCT01010061\] includes the analysis of 2 of the 3 arms obinutuzumab plus chlorambucil (Glb) compared to chlorambucil (Clb) reported here. * BO21004 (Stage 1b) \[NCT01998880\] includes the analysis of 2 of the 3 arms rituximab plus chlorambucil (RClb) compared to chlorambucil (Clb) reported separately. * BO21004 (Stage 2) \[NCT02053610\] includes the analysis of 2 of the 3 arms obinutuzumab plus chlorambucil (Glb) compared to rituximab plus chlorambucil (RClb) reported separately.
Source references
- references
- citation
- Langerbeins P, Giza A, Robrecht S, Cramer P, von Tresckow J, Al-Sawaf O, Fink AM, Furstenau M, Kutsch N, Simon F, Goede V, Hoechstetter M, Niemann CU, da Cunha-Bang C, Kater A, Dubois J, Gregor M, Staber PB, Tausch E, Schneider C, Stilgenbauer S, Eichhorst B, Fischer K, Hallek M. Reassessing the chronic lymphocytic leukemia International Prognostic Index in the era of targeted therapies. Blood. 2024 Jun 20;143(25):2588-2598. doi: 10.1182/blood.2023022564.
- pmid
- 38620092
- type
- DERIVED
- citation
- Jaramillo S, Agathangelidis A, Schneider C, Bahlo J, Robrecht S, Tausch E, Bloehdorn J, Hoechstetter M, Fischer K, Eichhorst B, Goede V, Hallek M, Dohner H, Rosenquist R, Ghia P, Stamatopoulos K, Stilgenbauer S. Prognostic impact of prevalent chronic lymphocytic leukemia stereotyped subsets: analysis within prospective clinical trials of the German CLL Study Group (GCLLSG). Haematologica. 2020 Nov 1;105(11):2598-2607. doi: 10.3324/haematol.2019.231027.
- pmid
- 33131249
- type
- DERIVED
- citation
- Gibiansky E, Gibiansky L, Buchheit V, Frey N, Brewster M, Fingerle-Rowson G, Jamois C. Pharmacokinetics, exposure, efficacy and safety of obinutuzumab in rituximab-refractory follicular lymphoma patients in the GADOLIN phase III study. Br J Clin Pharmacol. 2019 Sep;85(9):1935-1945. doi: 10.1111/bcp.13974. Epub 2019 Jul 12.
- pmid
- 31050355
- type
- DERIVED
- citation
- Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, Chagorova T, de la Serna J, Dilhuydy MS, Illmer T, Opat S, Owen CJ, Samoylova O, Kreuzer KA, Stilgenbauer S, Dohner H, Langerak AW, Ritgen M, Kneba M, Asikanius E, Humphrey K, Wenger M, Hallek M. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014 Mar 20;370(12):1101-10. doi: 10.1056/NEJMoa1313984. Epub 2014 Jan 8.
- pmid
- 24401022
- type
- DERIVED
Source notices and limitations
Discovery and provenance
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Preserved source evidence · Not medical advice