- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku, Calquence (acalabrutinib) / AstraZeneca
New P2 trial: Acalabrutinib and Venetoclax With or Without Early Obinutuzumab for the Treatment of High Risk, Recurrent, or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma (clinicaltrials.gov) - Nov 20, 2019
P2, N=168, Not yet recruiting,
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Trial completion date, Combination therapy: A Study of Venetoclax in Combination With Obinutuzumab in Participants With Chronic Lymphocytic Leukemia (clinicaltrials.gov) - Nov 19, 2019
P1, N=82, Active, not recruiting,
Trial primary completion date: Dec 2019 --> Jan 2019 Trial completion date: Aug 2019 --> Dec 2019
- |||||||||| Journal, IO biomarker: Tailored Treatment Strategies for Chronic Lymphocytic Leukemia in a Rapidly Changing Era. (Pubmed Central) - Nov 19, 2019
This article summarizes the most promising clinical advances by reviewing the data from recent clinical trials and discussing meaningful clinical endpoints, including the role of minimal residual disease assessment. The recent development of therapies targeting dysregulated pathways is revolutionary and may ultimately lead us to not only achieve prolonged remission durations but also envision the possibility of a functional cure for a larger population of patients.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Gazyva (obinutuzumab) / Roche, Biogen, Calquence (acalabrutinib) / AstraZeneca
Clinical, P2 data, Journal: Preliminary Safety and Efficacy Results from a Phase 2 Study of Acalabrutinib, Venetoclax and Obinutuzumab in Patients with Previously Untreated Chronic Lymphocytic Leukemia (CLL). (Pubmed Central) - Nov 18, 2019
Davids:AbbVie, Acerta Pharma, Adaptive, Biotechnologies, Astra-Zeneca, Genentech, Gilead Sciences, Janssen, Pharmacyclics, TG therapeutics: Membership on an entity's Board of Directors or advisory committees; AbbVie, Astra-Zeneca, Genentech, Janssen, MEI, Pharmacyclics, Syros Pharmaceuticals, Verastem: Consultancy; Acerta Pharma, Ascentage Pharma, Genentech, MEI pharma, Pharmacyclics, Surface Oncology, TG Therapeutics, Verastem: Research Funding; Research to Practice: Honoraria. Acalabrutinib, venetoclax, obinutuzumab - combination therapy for previously untreated CLL.
- |||||||||| Leukeran (chlorambucil) / GSK, Gazyva (obinutuzumab) / Roche, Biogen, Calquence (acalabrutinib) / AstraZeneca
Clinical, P3 data, Journal: ELEVATE TN: Phase 3 Study of Acalabrutinib Combined with Obinutuzumab (O) or Alone Vs O Plus Chlorambucil (Clb) in Patients (Pts) with Treatment-Naive Chronic Lymphocytic Leukemia (CLL). (Pubmed Central) - Nov 18, 2019
Wong:Acerta Pharma: Employment. Byrd:Genentech: Research Funding; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; Novartis: Other: Travel Expenses, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; Novartis: Other: Travel Expenses, Speakers Bureau; Novartis: Other: Travel Expenses, Speakers Bureau; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; Ohio State University: Patents & Royalties: OSU-2S; Ohio State University: Patents & Royalties: OSU-2S; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Genentech: Research Funding; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Genentech: Research Funding; Acerta: Research Funding; Acerta: Research Funding; Acerta: Research Funding; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Ohio State University: Patents & Royalties: OSU-2S; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; BeiGene: Research Funding; BeiGene: Research Funding; BeiGene: Research Funding; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau.
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku, Imbruvica (ibrutinib) / AbbVie, J&J
Enrollment closed, Combination therapy: A Study of Ibrutinib + Obinutuzumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia (clinicaltrials.gov) - Nov 15, 2019
P1, N=50, Active, not recruiting,
Byrd:Genentech: Research Funding; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; Novartis: Other: Travel Expenses, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; Novartis: Other: Travel Expenses, Speakers Bureau; Novartis: Other: Travel Expenses, Speakers Bureau; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; Ohio State University: Patents & Royalties: OSU-2S; Ohio State University: Patents & Royalties: OSU-2S; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Genentech: Research Funding; Pharmacyclics LLC, an AbbVie Company: Other: Travel Expenses, Research Funding, Speakers Bureau; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; TG Therapeutics: Other: Travel Expenses, Research Funding, Speakers Bureau; Genentech: Research Funding; Acerta: Research Funding; Acerta: Research Funding; Acerta: Research Funding; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Ohio State University: Patents & Royalties: OSU-2S; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; Janssen: Consultancy, Other: Travel Expenses, Research Funding, Speakers Bureau; BeiGene: Research Funding; BeiGene: Research Funding; BeiGene: Research Funding; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau; Gilead: Other: Travel Expenses, Research Funding, Speakers Bureau. Recruiting --> Active, not recruiting
- |||||||||| cyclophosphamide intravenous / Generic mfg., Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Biomarker, Clinical, Journal, IO biomarker: Integration of COO into the clinical CNS International Prognostic Index could improve CNS relapse prediction in DLBCL. (Pubmed Central) - Nov 14, 2019
P3
CNS relapse was analyzed in 1418 DLBCL patients treated with obinutuzumab or rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone chemotherapy in the phase 3 GOYA study...Combining high CNS-IPI and ABC/unclassified COO improved CNS relapse prediction and identified a patient subgroup at high risk of developing CNS relapse. The study is registered to https://clinicaltrials.gov as NCT01287741.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Gazyva (obinutuzumab) / Roche, Biogen, Imbruvica (ibrutinib) / AbbVie, J&J
Enrollment closed, Trial completion date, Trial primary completion date, Combination therapy: Bcl-2 Inhibitor GDC-0199 in Combination With Obinutuzumab and Ibrutinib in Treating Patients With Relapsed, Refractory, or Previously Untreated Chronic Lymphocytic Leukemia (clinicaltrials.gov) - Nov 14, 2019
P1/2, N=87, Active, not recruiting,
The study is registered to https://clinicaltrials.gov as NCT01287741. Trial completion date: Aug 2020 --> Aug 2021 | Trial primary completion date: Aug 2019 --> Aug 2020 | Recruiting --> Active, not recruiting
- |||||||||| Gazyva (obinutuzumab) / Roche, Biogen, Nippon Shinyaku
Trial completion date, Trial primary completion date: Lenalidomide and Obinutuzumab in Treating Patients With Relapsed Indolent Non-Hodgkin Lymphoma (clinicaltrials.gov) - Nov 11, 2019
P1/2, N=72, Active, not recruiting,
Trial completion date: Aug 2020 --> Aug 2021 | Trial primary completion date: Aug 2019 --> Aug 2020 | Recruiting --> Active, not recruiting Trial completion date: May 2019 --> May 2021 | Trial primary completion date: May 2019 --> May 2021
- |||||||||| Gazyva (obinutuzumab) / Biogen, Roche, Rituxan (rituximab) / Roche, Biogen
PERSISTENT HYPOGAMMAGLOBULINEMIA FOLLOWING OBINUTUZUMAB TREATMENT FOR CHRONIC LYMPHOCYTIC LEUKEMIA (Monitor 4) - Nov 9, 2019 - Abstract #ACAAI2019ACAAI_758;
Discussion Long-term impact of obinutuzumab on immunoglobulin levels has not been well studied; our case report presents an association with persistent hypogammaglobulinemia and complete peripheral B-cell depletion. Patients who require this anti B-cell monoclonal antibody therapy should have quantitative immunoglobulin levels & B-cell number and function monitored before and after treatment.
- |||||||||| cyclophosphamide intravenous / Generic Mfg., Rituxan (rituximab) / Roche, Biogen
Journal: The Treatment of Chronic Lymphatic Leukemia. (Pubmed Central) - Nov 8, 2019
Recent progress in the development of novel treatment options gives hope that CLL may soon be a controllable disease. Even at present, chemoimmuno- therapy can achieve a progression-free survival of more than eight years in certain genetically defined subgroups of CLL patients.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Gazyva (obinutuzumab) / Biogen, Roche, Rituxan (rituximab) / Roche, Biogen
Cost-Effectiveness of a 12-Month Fixed Duration of Venetoclax in Combination with Obinutuzumab in First-Line Chronic Lymphocytic Leukemia in the United States (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_6500;
P3
VenG is projected to be cost-effective vs. ClbG within accepted US cost-effectiveness thresholds. Compared with BR and IBR-based treat-to-progression regimens (IBR, IR, and IG), a 12-month fixed-duration treatment option with VenG seems cost saving and more efficacious based on the CEM.
- |||||||||| A Phase 3 Trial Comparing the Efficacy and Safety of Acalabrutinib in Combination with Venetoclax with or without Obinutuzumab, Compared with Investigator’s Choice of Chemoimmunotherapy in Patients with Previously Untreated Chronic Lymphocytic Leukemia (CLL) without Del(17p) or TP53 Mutation (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_6063;
P3
Recently completed phase 3 trials showed acalabrutinib ± obinutuzumab (obi) improved PFS vs chemotherapy in untreated patients (ELEVATE TN: AstraZeneca Press release 06/06/2019), and acalabrutinib improved PFS vs idelalisib or bendamustine + rituximab in relapsed/refractory patients (ASCEND: Ghia et al...In the phase 3 CLL-14 trial in untreated patients with CLL, fixed duration treatment with obi (6 months) + ven (12 months) was more efficacious than obi (6 months) + chlorambucil (12 months), achieving a longer PFS and higher rate of uMRD (Fischer et al...Study design and ACE-CL-311 (NCT03836261) is a 3-arm phase 3, randomized (1:1:1), global, multicenter, open-label trial evaluating the efficacy and safety of acalabrutinib + ven (Arm A) vs acalabrutinib + ven + obi (Arm B) vs CIT (Arm C: fludarabine/cyclophosphamide/rituximab [FCR; only for patients ≤ 65 years of age] or bendamustine/rituximab [BR])...Key exclusion criteria include stroke or intracranial hemorrhage, significant cardiovascular disease (asymptomatic or controlled atrial fibrillation allowed), bleeding disorders, or a requirement for treatment with warfarin or equivalent vitamin K antagonists or a strong cytochrome P450 inhibitor...The study is powered to achieve ~90% power to detect a hazard ratio of 0.65 in PFS comparing Arm A to Arm C, assuming median PFS of 44.7 months in FCR/BR at the 2-sided significance level of 0.05. Patients will be stratified based on age (>65 vs ≤65 years), IGHV mutational status (mutated vs unmutated), Rai stage risk (high [≥3] vs non-high [<3]), and geographic location (North America vs Europe vs Other).
- |||||||||| Gazyva (obinutuzumab) / Biogen, Roche, Rituxan (rituximab) / Roche, Biogen, bendamustine / SymBio, Mundipharma, Astellas, Generic mfg.
Final Results from the Multicenter, Open-Label, Phase II GIBB Study of Obinutuzumab+Bendamustine in Previously Untreated Patients with Chronic Lymphocytic Leukemia (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_6062;
P2
Complete response and MRD− in peripheral blood were achieved in approximately half of all patients after induction treatment and persisted over time. IgVH mutated status was associated with a longer duration of MRD− and median PFS.
- |||||||||| Rituxan (rituximab) / Roche, Biogen
IL-21-Expanded NK Cells As Autologous Cell Therapy for CLL (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_6048;
These patient-derived cells are superior to normal unstimulated NKs and are similar or even better than expanded donor NK cells . Ongoing studies will explore in vivo function of these NK cells, combination with CLL-targeted treatments, and further functional measures .
- |||||||||| Rituxan (rituximab) / Roche, Biogen
IL-21-Expanded Natural Killer Cells As Autologous Cell Therapy for CLL (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_6047;
These patient-derived cells are superior to normal unstimulated NKs and are similar or even better than expanded donor NK cells . Ongoing studies will explore in vivo function of these NK cells, combination with CLL-targeted treatments, and further functional measures .
- |||||||||| tirabrutinib (GS-4059) / Ono Pharma, Gilead, Gazyva (obinutuzumab) / Biogen, Roche, entospletinib (GS-9973) / Gilead
A Prospective, Open-Label, Multicenter, Phase 2 Trial to Evaluate the Safety and Efficacy of the Combination of Tirabrutinib (ONO/GS-4059) and Entospletinib with and without Obinutuzumab in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_6042;
P2
There was a male predominance (1.89:1), 28% were above age 65 with a median age of 61 years (range 24-87), and CLL-IPI score was Low and Intermediate to Very High in 43.6% (130/298) and 56.4% (168/298), respectively. =VLOOKUP($B5614,[1]!Table1[[#All],[MID]:[Details]],2,0)
- |||||||||| doxorubicin hydrochloride / Generic mfg., Rituxan (rituximab) / Roche, Biogen
Patient-Level Meta-Analysis of End-of-Therapy PET-CR as a Surrogate Endpoint for PFS and OS in Patients with Previously Untreated DLBCL: Implications for Clinical Trial Design (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_5837;
P1/2, P2,
The estimated HR is 0.13 for PFS, PET-CR versus nonCR, and it is 0.10 for OS. Based on our model, a treatment that improves PET-CR rate could be reasonably expected to have a benefit on PFS and OS, for the populations we considered.
- |||||||||| Polivy (polatuzumab vedotin) / Roche, Seattle Genetics, Rituxan (rituximab) / Roche, Biogen
Polatuzumab Vedotin, an Antibody-Drug Conjugate Targeting CD79b, Is a Highly Active Agent Against Burkitt Lymphoma and Primary Mediastinal B-Cell Lymphoma (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_5695;
The use of short and intense multiagent chemotherapy alone and in combination with rituximab (R) results in ≥90% event-free survival (EFS) in children and adolescents with BL and DLBCL (Cairo et al, JCO, 2012; Goldman/Cairo Leukemia, 2013; BJH, 2014)...We previously demonstrated that Obinutuzumab (O), a new type II anti-CD20 monoclonal antibody, is an active agent against both BL and PMBL (Awasthi/Cairo et al, BJH, 2015)...These preclinical results suggest that PV should be considered for investigation in patients with both recurrent/refractory BL and PMBL and in patients with newly diagnosed disease with either high risk features or those with poor responses to induction therapy . Authors AA, MB & AA are all considered co-primary first authors
- |||||||||| Gazyva (obinutuzumab) / Biogen, Roche, bendamustine / SymBio, Mundipharma, Astellas, Generic mfg.
Improvements in Health-Related Quality of Life and Symptoms in Patients with Previously Untreated Chronic Lymphocytic Leukemia: Final Results from the Phase II GIBB Study of the Combination of Obinutuzumab and Bendamustine (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_4702;
P2
The HRQoL data from the GIBB trial suggest that G-Benda treatment consistently improved patient HRQoL over time. Several clinically meaningful improvements were observed in HRQoL, including global health status, functioning, symptoms, and future health worries.
- |||||||||| rhIL-15 / National Cancer Institute, Gazyva (obinutuzumab) / Biogen, Roche, Rituxan (rituximab) / Roche, Biogen
Phase 1 Trial of Human IL-15 (rhIL-15) and Obinutuzumab for Relapsed and Refractory Chronic Lymphocytic Leukemia (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_4244;
Obinutuzumab is a glycoengineered, humanized type 2 anti-CD20 monoclonal antibody thought to engage the immune system by directly activating antibody- dependent, cell-mediated cytotoxicity (ADCC); it is approved for treatment of chronic lymphocytic leukemia in combination with chlorambucil...Preclinical murine lymphoid malignancy models have shown increased efficacy of monoclonal antibodies when administered together with rhIL-15; BL/6 mice inoculated with EL4-CD20 cells (a syngeneic lymphoma line); including significant prolongation of survival with the IL-15/Rituximab combination compared to either drug given as single agent (90% v...Primary objective: determine the safety, toxicity profile, dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD) of civ rhIL-15 administration in combination with obinutuzumab treatment Secondary objectives: 1) evaluate the potential antitumor activity of the combination of rhIL-15 and obinutuzumab by assessing the clinical response rate, minimal residual disease (MRD) status, progression-free survival, and overall survival in patients with relapsed and refractory CLL; 2) define the effects of rhIL-15 on the ADCC mediated by obinutuzumab using ex vivo peripheral blood mononuclear cells (PBMCs); 3) characterize the biological effects of rhIL-15 administered with obinutuzumab on the percentages and absolute numbers of circulating lymphocytes (T and NK cells) and the T- cell subsets (including naïve, central, and effector memory subsets) by flow cytometry Exploratory objectives: identify biomarkers predictive of response to rhIL-15 and obinutuzumab treatment, such as circulating tumor DNA (ctDNA) and baseline cytokine levels Eligibility criteria: 1) age ≥ 18 years; 2) ECOG ≤ 1; 3) Diagnosis of CLL or small lymphocytic lymphoma (SLL) with ≥ 50% of B cells expressing CD20; 4) measurable or evaluable disease that is refractory or relapsed following therapy with a BTK inhibitor OR have relapsed/refractory CLL and are intolerant to BTK inhibitor therapy; patients with del(17p) must also be refractory or relapsed after, or intolerant to, therapy with venetoclax; 5) adequate organ function parameters as defined within the protocol; 6) active disease requiring treatment, as defined within the protocol...One patient has started treatment to date . Enrollment is ongoing.
- |||||||||| BTK and/or PLCG2 Mutations in Patients with Chronic Lymphocytic Leukemia (CLL) Treated with Ibrutinib: Characteristics and Outcomes at the Time of Progression (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_4242;
Therapy following progression on ibrutinib in these pts was as follows: venetoclax (n=16; 11 pts who continued ibrutinib in combination), idelalisib (n=4), investigational treatments (n=2), continued ibrutinib alone (n=2), dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab; n=1), and unknown (n=1)...Treatment of these patients consisted of the following: restarted ibrutinib in addition to current treatment of venetoclax (n=5), venetoclax (n=2), pembrolizumab (n=2; 1 pt with continued ibrutinib), obinutuzumab with continued ibrutinib (n=1), gemcitabine and vinorelbine with continued ibrutinib (n=1), and no further treatment (n=1)...Treatments following progression on ibrutinib included multi-agent chemoimmunotherapy (n=3; 2 pts received rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone [R-CHOP] with continued ibrutinib and 1 pt received doxorubicin, bleomycin, vinblastine, dacarbazine [ABVD] alone), pembrolizumab (n=3; 1 pt in combination with continued ibrutinib), venetoclax in combination with continued ibrutinib (n=1), and venetoclax and obinutuzumab (n=1)...CONCLUSION Approximately 60% of pts tested in this progression cohort had a BTK or PLCG2 mutation at time of or preceding progression on ibrutinib therapy. OS and time to next therapy did not differ statistically between pts with mutated vs non-mutated clones; however, caution should be applied with the conclusions given the limited sample size.
- |||||||||| tirabrutinib (GS-4059) / Ono Pharma, Gilead, Gazyva (obinutuzumab) / Biogen, Roche, Zydelig (idelalisib) / Gilead
A Prospective, Open-Label, Multicenter, Phase 2 Trial to Evaluate the Safety and Efficacy of the Combination of Tirabrutinib (ONO/GS-4059) and Idelalisib with and without Obinutuzumab in Patients with Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL) (Hall B, Level 2 (Orange County Convention Center)) - Nov 7, 2019 - Abstract #ASH2019ASH_4239;
P2
OS and time to next therapy did not differ statistically between pts with mutated vs non-mutated clones; however, caution should be applied with the conclusions given the limited sample size. =VLOOKUP($B3817,[1]!Table1[[#All],[MID]:[Details]],2,0)
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