Trial Outcomes & Findings for A Study Evaluating the Efficacy of Obinutuzumab and Bendamustine Treatment in Participants With Refractory or Relapsed Chronic Lymphocytic Leukemia (NCT NCT02071225)

NCT ID: NCT02071225

Last Updated: 2020-02-07

Results Overview

ORR was defined as percentage of participants achieving Complete Response (CR), incomplete CR (CRi) or Partial Response (PR). CR: lymphocytes below 4 x 10\^9/L, absence of lymphadenopathy, hepatomegaly and splenomegaly, absence of disease or constitutional symptoms, neutrophils \> 1.5 x 10\^9/L, platelets \> 100 x 10\^9/L, hemoglobin \> 110 g/L, bone marrow at least normocellular for age. CRi: CR with persistent cytopenia, i.e. anemia, thrombocytopenia and/or neutropenia. PR: reduction ≥ 50% of the lymphocyte count AND reduction ≥ 50% of the lymphadenopathy OR reduction ≥ 50% of the size of the liver if enlarged at baseline OR reduction ≥ 50% of the size of the spleen if enlarged at baseline PLUS one of the following: neutrophils \> 1.5 x 10\^9/L, platelets \> 100 x 10\^9/L, hemoglobin \> 110 g/L or increase ≥ 50% compared to pre-treatment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

72 participants

Primary outcome timeframe

2-3 months after last dose of the study treatment (up to approximately 9 months)

Results posted on

2020-02-07

Participant Flow

A total of 72 participants were recruited at 20 sites in Spain.

Participants enrolled in the study had documented CD20-positive B-cell type relapsed or refractory chronic lymphocytic leukemia (CLL).

Participant milestones

Participant milestones
Measure	Obinutuzumab + Bendamustine Participants received obinutuzumab and bendamustine in 28-days cycles for a maximum of 6 cycles.
Overall Study STARTED	72
Overall Study COMPLETED	42
Overall Study NOT COMPLETED	30

Reasons for withdrawal

Reasons for withdrawal
Measure	Obinutuzumab + Bendamustine Participants received obinutuzumab and bendamustine in 28-days cycles for a maximum of 6 cycles.
Overall Study Withdrawal of Consent	2
Overall Study Protocol Deviation	1
Overall Study Lost to Follow-up	2
Overall Study Death	25

Baseline Characteristics

A Study Evaluating the Efficacy of Obinutuzumab and Bendamustine Treatment in Participants With Refractory or Relapsed Chronic Lymphocytic Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Obinutuzumab + Bendamustine n=72 Participants Participants received obinutuzumab and bendamustine in 28-days cycles for a maximum of 6 cycles.
Age, Continuous	67.9 years n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants
Sex: Female, Male Male	48 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	71 Participants n=5 Participants
Race/Ethnicity, Customized Indian	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2-3 months after last dose of the study treatment (up to approximately 9 months)

Population: Efficacy population included all participants, who received at least one dose of both treatments (bendamustine and obinutuzumab).

Outcome measures

Outcome measures
Measure	Obinutuzumab + Bendamustine n=70 Participants Participants received obinutuzumab and bendamustine in 28-days cycles for a maximum of 6 cycles.
Overall Response Rate (ORR) as Assessed by the Investigator Using the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Criteria	78.6 percentage of participants Interval 66.8 to 87.1

SECONDARY outcome

Timeframe: During study treatment and until 6 months after end of study treatment at approximately 12 months

Population: Efficacy population included all participants, who received at least one dose of both treatments (bendamustine and obinutuzumab). Reported here is the number of participants for whom data for best response achieved were available.

Best overall response was defined as percentage of participants achieving a best response of CR, CRi and PR. CR: lymphocytes below 4 x 10\^9/L, absence of lymphadenopathy, hepatomegaly and splenomegaly, absence of disease or constitutional symptoms, neutrophils \> 1.5 x 10\^9/L, platelets \> 100 x 10\^9/L, hemoglobin \> 110 g/L, bone marrow at least normocellular for age. CRi: CR with persistent cytopenia, i.e. anemia, thrombocytopenia and/or neutropenia. PR: reduction ≥ 50% of the lymphocyte count AND reduction ≥ 50% of the lymphadenopathy OR reduction ≥ 50% of the size of the liver if enlarged at baseline OR reduction ≥ 50% of the size of the spleen if enlarged at baseline PLUS one of the following: neutrophils \> 1.5 x 10\^9/L, platelets \> 100 x 10\^9/L, hemoglobin \> 110 g/L or increase ≥ 50% compared to pre-treatment.

Outcome measures

Outcome measures
Measure	Obinutuzumab + Bendamustine n=54 Participants Participants received obinutuzumab and bendamustine in 28-days cycles for a maximum of 6 cycles.
Best Response Rate as Assessed by the Investigator Using the IWCLL 2008 Criteria CR	46.3 percentage of participants
Best Response Rate as Assessed by the Investigator Using the IWCLL 2008 Criteria CRi	1.9 percentage of participants
Best Response Rate as Assessed by the Investigator Using the IWCLL 2008 Criteria PR	42.6 percentage of participants

SECONDARY outcome

Timeframe: From start of treatment up to disease progression or relapse or death, whichever occurred first (up to approximately 4.5 years)

Population: Efficacy population included all participants, who received at least one dose of both treatments (bendamustine and obinutuzumab).

PFS is defined as the time from the start of treatment to disease progression (DP), relapse or death from any cause, whichever occurs first, as assessed by the investigator. DP: at least one of the following characteristics: increase ≥ 50% in lymphocytes up to at least 5 x 10\^9/L, appearance of new palpable lymph nodes, increase ≥ 50% of the longest diameter of any previous area of clinically significant lymphadenopathy, increase ≥ 50% of the size of the liver and/or spleen, transformation to a more aggressive histology, after treatment progression of any cytopenia: decrease of hemoglobin levels of more than 20 g/L or to below 100 g/L and/or decrease of platelet counts by more than 50% or to below 100 x 10\^9/L and/or decrease in the neutrophil counts by more than 50% or to below 1.0 x 10\^9/L if the marrow biopsy also shows infiltration of clonal chronic lymphocytic leukemia (CLL) cells.

Outcome measures

Outcome measures
Measure	Obinutuzumab + Bendamustine n=70 Participants Participants received obinutuzumab and bendamustine in 28-days cycles for a maximum of 6 cycles.
Progression Free Survival (PFS)	24.14 months Interval 20.81 to 27.47

SECONDARY outcome

Timeframe: From start of treatment up to death of any cause (up to approximately 4.5 years)

Population: Efficacy population included all participants, who received at least one dose of both treatments (bendamustine and obinutuzumab).

OS was defined as the time from the start of study treatment to death from any cause.

Outcome measures

Outcome measures
Measure	Obinutuzumab + Bendamustine n=70 Participants Participants received obinutuzumab and bendamustine in 28-days cycles for a maximum of 6 cycles.
Overall Survival (OS)	NA months Median of OS for efficacy population was not reached.

SECONDARY outcome

Timeframe: From start of treatment up to disease progression or relapse or death or start of a new anti-leukemic therapy, whichever occurred first (up to approximately 4.5 years)

Population: Efficacy population included all participants, who received at least one dose of both treatments (bendamustine and obinutuzumab).

EFS was defined as the time from the start of treatment to DP/relapse, death from any cause or start of a new anti-leukemia therapy. DP: at least one of the following characteristics: increase ≥ 50% in lymphocytes up to at least 5 x 10\^9/L, appearance of new palpable lymph nodes, increase ≥ 50% of the longest diameter of any previous area of clinically significant lymphadenopathy, increase ≥ 50% of the size of the liver and/or spleen, transformation to a more aggressive histology, after treatment, progression of any cytopenia: decrease of hemoglobin levels of more than 20 g/L or to below 100 g/L and/or decrease of platelet counts by more than 50% or to below 100 x 10\^9/L and/or decrease in the neutrophil counts by more than 50% or to below 1.0 x 10\^9/L if the marrow biopsy also shows infiltration of clonal CLL cells.

Outcome measures

Outcome measures
Measure	Obinutuzumab + Bendamustine n=70 Participants Participants received obinutuzumab and bendamustine in 28-days cycles for a maximum of 6 cycles.
Event Free Survival (EFS)	24.14 months Interval 19.96 to 28.32

SECONDARY outcome

Timeframe: From occurrence of complete response up to disease progression or death, whichever occurred first (up to approximately 4.5 years)

Population: Efficacy population included all participants, who received at least one dose of both treatments (bendamustine and obinutuzumab). Included in the analysis are participants who achieved CRi or CR.

DFS was defined for all participants who achieved complete response (CRi or CR). DFS lasted from the date on which CRi or CR was recorded until the date on which the first DP or death from any cause occurred. DP: at least one of the following characteristics: increase ≥ 50% in lymphocytes up to at least 5 x 10\^9/L, appearance of new palpable lymph nodes, increase ≥ 50% of the longest diameter of any previous area of clinically significant lymphadenopathy, increase ≥ 50% of the size of the liver and/or spleen, transformation to a more aggressive histology, after treatment, progression of any cytopenia: decrease of hemoglobin levels of more than 20 g/L or to below 100 g/L and/or decrease of platelet counts by more than 50% or to below 100 x 10\^9/L and/or decrease in the neutrophil counts by more than 50% or to below 1.0 x 10\^9/L if the marrow biopsy also shows infiltration of clonal CLL cells.

Outcome measures

Outcome measures
Measure	Obinutuzumab + Bendamustine n=25 Participants Participants received obinutuzumab and bendamustine in 28-days cycles for a maximum of 6 cycles.
Disease Free Survival (DFS)	23.02 months Interval 21.38 to 24.66

SECONDARY outcome

Timeframe: From occurrence of CR or PR up to disease progression or death, whichever occurred first (up to approximately 4.5 years)

DR was defined for participants with CRi, CR or PR. DR spanned from the date on which response was recorded until the date on which DP or death from any cause occurred. DP: at least one of the following characteristics: increase ≥ 50% in lymphocytes up to at least 5 x 10\^9/L, appearance of new palpable lymph nodes, increase ≥ 50% of the longest diameter of any previous area of clinically significant lymphadenopathy, increase ≥ 50% of the size of the liver and/or spleen, transformation to a more aggressive histology, after treatment, progression of any cytopenia: decrease of hemoglobin levels of more than 20 g/L or to below 100 g/L and/or decrease of platelet counts by more than 50% or to below 100 x 10\^9/L and/or decrease in the neutrophil counts by more than 50% or to below 1.0 x 10\^9/L if the marrow biopsy also shows infiltration of clonal CLL cells.

Outcome measures

Outcome measures
Measure	Obinutuzumab + Bendamustine n=54 Participants Participants received obinutuzumab and bendamustine in 28-days cycles for a maximum of 6 cycles.
Duration of Response (DR)	21.41 months Interval 17.6 to 25.22

SECONDARY outcome

Timeframe: Up to 4.5 years

Population: Efficacy population included all participants, who received at least one dose of both treatments (bendamustine and obinutuzumab).

Time to re-treatment/new leukemia therapy was defined as the time between the start of treatment and the date of the first administration of re-treatment or new leukemia therapy.

Outcome measures

Outcome measures
Measure	Obinutuzumab + Bendamustine n=70 Participants Participants received obinutuzumab and bendamustine in 28-days cycles for a maximum of 6 cycles.
Time to Re-treatment/New Anti-leukemia Therapy	NA months Median of time to re-treatment for efficacy population was not reached.

SECONDARY outcome

Timeframe: At approximately 9 months

Population: ITT population included all participants, who received at least one dose of any treatment.

MRD negativity was defined as the presence of less than 1 cell of CLL per 10,000 leukocytes (= category 0, \<0.01%) assessed in bone marrow (BM) and peripheral blood (PB) by flow cytometry after the end of the treatment at the final response assessment.