Last reviewed · How we verify

NCT02071225

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

Completed Phase 2 Results posted Last updated 7 February 2020
What this trial tests

Phase 2 trial testing bendamustine in Chronic Lymphocytic Leukemia in 72 participants. Completed in 19 November 2018.

Timeline
9 April 2014
Primary endpoint
19 November 2018
19 November 2018

Quick facts

Lead sponsorHoffmann-La Roche
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment72
Start date9 April 2014
Primary completion19 November 2018
Estimated completion19 November 2018
Sites21 locations across Spain

Drugs / interventions tested

Conditions studied

Sponsor

Hoffmann-La Roche — full company profile →

Who can join

18 and older, any sex, with Chronic Lymphocytic Leukemia. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Overall Response Rate (ORR) as Assessed by the Investigator Using the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 Criteria Primary · 2-3 months after last dose of the study treatment (up to approximately 9 months)

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 th

GroupValue95% CI
Obinutuzumab + Bendamustine78.666.8 – 87.1
Best Response Rate as Assessed by the Investigator Using the IWCLL 2008 Criteria Secondary · During study treatment and until 6 months after end of study treatment at approximately 12 months

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 enlarg

CR
GroupValue95% CI
Obinutuzumab + Bendamustine46.3
CRi
GroupValue95% CI
Obinutuzumab + Bendamustine1.9
PR
GroupValue95% CI
Obinutuzumab + Bendamustine42.6
Progression Free Survival (PFS) Secondary · From start of treatment up to disease progression or relapse or death, whichever occurred first (up to approximately 4.5 years)

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 lev

GroupValue95% CI
Obinutuzumab + Bendamustine24.1420.81 – 27.47
Overall Survival (OS) Secondary · From start of treatment up to death of any cause (up to approximately 4.5 years)

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

GroupValue95% CI
Obinutuzumab + BendamustineNANA – NA
Event Free Survival (EFS) Secondary · 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)

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

GroupValue95% CI
Obinutuzumab + Bendamustine24.1419.96 – 28.32
Disease Free Survival (DFS) Secondary · From occurrence of complete response up to disease progression or death, whichever occurred first (up to approximately 4.5 years)

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 c

GroupValue95% CI
Obinutuzumab + Bendamustine23.0221.38 – 24.66
Duration of Response (DR) Secondary · 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

GroupValue95% CI
Obinutuzumab + Bendamustine21.4117.60 – 25.22
Time to Re-treatment/New Anti-leukemia Therapy Secondary · Up to 4.5 years

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.

GroupValue95% CI
Obinutuzumab + BendamustineNANA – NA
Percentage of Participants With Minimal Residual Disease (MRD) Negativity Secondary · At approximately 9 months

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.

MRD in BM: Cat 0
GroupValue95% CI
Obinutuzumab + Bendamustine36.4
MRD in PB: Cat 0
GroupValue95% CI
Obinutuzumab + Bendamustine53.4
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Secondary · Up to approximately 4.5 years

An AE is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. An SAE was any AE that was any of the following: fatal, life-threatening,

AEs
GroupValue95% CI
Obinutuzumab + Bendamustine94.4
SAEs
GroupValue95% CI
Obinutuzumab + Bendamustine51.4
Percentage of Participants With AEs of Special Interest (AESIs) Secondary · Up to approximately 4.5 years

AESIs included any of the following: SAEs associated with the infusion of obinutuzumab: obinutuzumab serious infusion-related reactions, which were defined as AEs occurring during or within 24 hours following the administration of an infusion of obinutuzumab and considered related to obinutuzumab; serious infection; serious neutropenia; any tumor lysis syndrome (TLS); second malignancies.

GroupValue95% CI
Obinutuzumab + Bendamustine45.8
Percentage of Participants With Infusion-related Reactions (IRRs) Secondary · Up to end of treatment at 6 months

IRRs were defined as AEs occurring during or within 24 hours following the administration of an infusion and considered related to drug treatment.

GroupValue95% CI
Obinutuzumab + Bendamustine20.8

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to approximately 4.5 years. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Obinutuzumab + Bendamustine
Serious: 37/72 (51%)
Deaths: 25/72

Serious adverse events (40 terms)

ReactionSystemObinutuzumab + Bendamustine
NeutropeniaBlood and lymphatic system disorders
Febrile neutropeniaBlood and lymphatic system disorders
PyrexiaGeneral disorders
PneumoniaInfections and infestations
Respiratory tract infectionInfections and infestations
Septic shockInfections and infestations
DiarrhoeaGastrointestinal disorders
Infusion related reactionGeneral disorders
Multiple organ dysfunction syndromeGeneral disorders
BronchitisInfections and infestations
SepsisInfections and infestations
Acute myeloid leukaemiaBlood and lymphatic system disorders
Acute myelomonocytic leukaemiaBlood and lymphatic system disorders
Haemophagocytic lymphohistiocytosisBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
DyspnoeaCardiac disorders
GastroenteritisGastrointestinal disorders
Upper gastrointestinal haemorrhageGastrointestinal disorders
CachexiaGeneral disorders
MalaiseGeneral disorders
Mucosal inflammationGeneral disorders
Abdominal SepsisInfections and infestations
Bronchopulmonary aspergillosisInfections and infestations
Lung InfectionInfections and infestations
Periorbital cellulitisInfections and infestations
Other adverse events (26 terms — click to expand)

ReactionSystemObinutuzumab + Bendamustine
NeutropeniaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
AstheniaGeneral disorders
PyrexiaGeneral disorders
Respiratory tract infectionInfections and infestations
NauseaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
Infusion related reactionGeneral disorders
CoughRespiratory, thoracic and mediastinal disorders
ConstipationGastrointestinal disorders
NasopharyngitisRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
VomitingGastrointestinal disorders
DyspnoeaCardiac disorders
Urinary tract infectionInfections and infestations
RashSkin and subcutaneous tissue disorders
Abdominal painGastrointestinal disorders
Herpes zosterInfections and infestations
Decreased appetiteMetabolism and nutrition disorders
Chest painCardiac disorders
Abdominal pain upperGastrointestinal disorders
HypertransaminasaemiaHepatobiliary disorders
HeadacheNervous system disorders
TremorNervous system disorders
HypotensionVascular disorders

Most-reported serious reactions: Neutropenia, Febrile neutropenia, Pyrexia, Pneumonia, Respiratory tract infection, Septic shock, Diarrhoea, Infusion related reaction.

Data from ClinicalTrials.gov NCT02071225 adverse events section.

Sponsor's own description

This phase II trial was designed to evaluate the efficacy of obinutuzumab and bendamustine treatment in participants with refractory or relapsed chronic lymphocytic leukemia (CLL). Participants receive up to six 28-day cycles of treatment. Treatment consists of intravenous (IV) administration of obinutuzumab and bendamustine. Treatment time is expected to last 6 months, and participant follow-up will last 2 years.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Obinutuzumab in chronic lymphocytic leukemia: design, development and place in therapy.
    Al-Sawaf O, Fischer K, Engelke A, Pflug N, et al · · 2017 · cited 13× · PMID 28182141 · DOI 10.2147/dddt.s104869
  2. Obinutuzumab for the treatment of chronic lymphocytic leukemia and other B-cell lymphoproliferative disorders.
    Said R, Tsimberidou AM. · · 2017 · cited 7× · PMID 28893099 · DOI 10.1080/14712598.2017.1377178
  3. Clinical role of obinutuzumab in the treatment of naive patients with chronic lymphocytic leukemia.
    Cerquozzi S, Owen C. · · 2015 · cited 4× · PMID 25733804 · DOI 10.2147/btt.s61600
  4. New developments in the treatment of chronic lymphocytic leukemia: role of obinutuzumab.
    Shah A. · · 2015 · cited 3× · PMID 26251607 · DOI 10.2147/tcrm.s71839
  5. Obinutuzumab: the more the merrier?
    Burger JA. · · 2016 · cited 2× · PMID 26744434 · DOI 10.1182/blood-2015-10-676882

Verify or expand the search:

Other trials of bendamustine

Trials testing the same drug.

Other recruiting trials for Chronic Lymphocytic Leukemia

Currently open trials in the same condition.

Other Hoffmann-La Roche trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02071225.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing