ACP-196 Displays A Favorable Safety Profile for Patients with Relapsed/Refractory CLL

Dr. Richard Furman
Dr. Richard Furman

This Phase 1/2 trial was designed to evaluate the safety profile and efficacy of orally administered ACP-196 in patients with relapsed or refractory CLL/SLL. ACP-196 is a second generation BTK inhibitor that is more selective than the first generation BTK inhibitor ibrutinib. Bruton’s tyrosine kinase (BTK) is an enzyme involved in B cell receptor pathway signaling that has been shown to be critical for CLL cell survival. Trials with ibrutinib established BTK as an effective therapeutic target for the treatment of CLL.

As part of the trial, patients were treated continuously with escalating doses of ACP-196, once or twice daily. No dose limiting toxicities were identified and 100 mg twice daily was established as the most efficacious dose. The median age of the patients and number of prior therapies were 62 years and 3 prior therapies respectively. The median time on the study was 10.3 months. As of June 2015 there were 60 patients who were evaluable for response.

The overall response rate was 93% for all patients and 100% in the deletion 17p patient. ACP-196 was well tolerated, with 93% of patients remaining on treatment. The most common adverse events were headache and diarrhea. No disease progression has occurred to date.

Results from this study show that ACP-196 is a highly potent and selective oral BTK inhibitor with a favorable safety profile. Currently there is a Phase 3 trial comparing ACP-196 to Ibrutinib in Patients with High Risk CLL open to eligible patients at Weill Cornell Medicine.

Weill Cornell Medicine Lymphoma Program Related Abstracts at ASH 2015

2015 has been another productive year for research in the Lymphoma Program at Weill Cornell Medicine. Listed below are the abstracts we were involved in whole or in part to be presented at this year’s 57th Annual Meeting of the American Society of Hematology (ASH) in December.

Look to this space for future updates about lymphoma related developments from ASH 2015.

B-cell Lymphomas

434 – A Chromatin Reader That Acts As a Key to Lock in and Coordinate Recruitment of Transcription Factors and a Novel Polycomb Complex to Bivalent Chromatin Thus Driving Formation of Germinal Centers and B-Cell Lymphomas

2427 – Transcriptome Sequencing Reveals Thousands of Novel Long Non-Coding RNAs in B-Cell Lymphoma

2756 – Scavenger Receptor Type B1 Is Essential for High Density Lipoprotein Nanoparticle Induced B-Cell Lymphoma Cell Death

Burkitt ’s lymphoma

592 – Targeting the Hsp90 Oncoproteome in Burkitt Lymphoma


831 – The Bruton Tyrosine Kinase (Btk) Inhibitor ACP-196:  Marked Activity in Relapsed/Refractory CLL with a Favorable Safety Profile

833 – Outcome of Ibrutinib Treatment by Baseline Genetic Features in Patients with Relapsed or Refractory CLL/SLL with del17p in the Resonate-17 Study

1728 – SLAMF1/CD150 Activates Autophagy in Chronic Lymphocytic Leukemia Cells, Modulating Chemotaxis and Responses to Therapy

2952 – Patterns of Lymphocytosis in Patients with Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Treated with Idelalisib

4145 – Adenosine Signaling Mediates Hypoxic Responses in the Chronic Lymphocytic Leukemia Microenvironment

4153 – Analysis of Prognostic Factors Predictive of Complete Response (CR) to Ibrutinib in Patients with CLL/SLL


811 – Randomized Phase 2 Open-Label Study of R-CHOP ± Bortezomib in Patients (Pts) with Untreated Non-Germinal Center B-Cell-like (Non-GCB) Subtype Diffuse Large Cell Lymphoma (DLBCL): Results from the Pyramid Trial (NCT00931918)

2739 – Phase II Randomized Study of Lenalidomide or Lenalidomide and Rituximab Following Standard Chemotherapy for Patients with Intermediate-High/High Risk Diffuse Large B-Cell Lymphoma (DLBCL) – Final Results

Follicular Lymphoma

334 – Interfollicular CD10 Expression and Follicular PD1 Tumor-Infiltrating Lymphocytes As Biologic Risk Factors in Patients with Previously Untreated Follicular Lymphoma Receiving Rituximab-Based Biologic Therapy: An Alliance Correlative Science Study (CALGB 50901, 50402, 50701, 50803, 50401)

471 – Phase I Study of Rituximab, Lenalidomide, and Ibrutinib in Previously Untreated Follicular Lymphoma (Alliance 051103)

2744 – Activity of Idelalisib in High-Risk Follicular Lymphoma with Early Relapse Following Front Line Immunochemotherapy

Hodgkin Lymphoma

519 – Post Transplant Outcome of a Multicenter Phase II Study of Brentuximab Vedotin As First Line Salvage Therapy in Relapsed/Refractory HL Prior to AHCT

578 – Initial Results of US Intergroup Trial of Response-Adapted Chemotherapy or Chemotherapy/Radiation Therapy Based on PET for Non-Bulky Stage I and II Hodgkin Lymphoma (HL) (CALGB/Alliance 50604)

2636 – Outcomes in Adolescents and Young Adults (AYA) with Hodgkin Lymphoma (HL) Treated on US Cooperative Group Protocols: An Adult Intergroup (E2496) and Children’s Oncology Group (COG AHOD0031) Comparative AnalysisClinically Relevant Abstract

2639 – The Landscape of microRNA Expression in HIV and Non-HIV Associated Classical Hodgkin Lymphoma through Next Generation Sequencing

Mantle Cell Lymphoma

337 – Bortezomib Maintenance (BM) Versus Consolidation (BC) Following Aggressive Immunochemotherapy and Autologous Stem Cell Transplant (ASCT) for Untreated Mantle Cell Lymphoma (MCL): CALGB (Alliance)50403

518 – Pre-Transplant R-Bendamustine Induces High Rates of Minimial Residual Disease in MCL Patients: Updated Results of S1106: US Intergroup Study of a Randomized Phase II Trial of R-HCVAD Vs. R-Bendamustine Followed By Autologous Stem Cell Transplants for Patients with Mantle Cell Lymphoma

4527- Clinical Impact of Internet-Based Tools to Help Guide Therapeutic Decisions for Mantle Cell Lymphoma (MCL)

Marginal Zone Lymphoma

1543  Idelalisib Monotherapy and Durable Responses in Patients with Relapsed or Refractory Marginal Zone Lymphoma (MZL)

Non-Hodgkin Lymphoma

258- Safety, Efficacy, and Determination of the Recommended Phase 2 Dose for the Oral Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330)

2741 – Phase II Trial of Ofatumumab (OFA) in Previously Untreated Follicular Non-Hodgkin Lymphoma (NHL): CALGB 50901 (Alliance)

3961 – Long-Term Outcomes, Secondary Malignancies, and Stem Cell Collection Following Bendamustine in Patients with Previously Treated Indolent Non-Hodgkin Lymphoma

T-Cell Lymphoma

341 – First Multicenter, Randomized Phase 3 Study in Patients (Pts) with Relapsed/Refractory (R/R) Peripheral T-Cell Lymphoma (PTCL): Alisertib (MLN8237) Versus Investigator’s Choice (Lumiere trial; NCT01482962)

1451 – Assessment of T-Cell Receptor Repertoire and Clonal Expansion in Peripheral T-Cell Lymphoma Using RNA-Seq Data

Waldenstrom’s Macroglobulinemia

703 – VLX1570, a First in Class Dub Inhibitor, Modulates BCR Signaling and CXCR4 Expression and Demonstrates Significant In Vivo Antitumor Activity in a Murine Model of Human Waldenstrom Macroglobulinemia

Dr. Richard Furman Discusses CLL/SLL Treatments with Lymphoma Research Foundation

Recently, CLL Program Director, Dr. Richard Furman discussed CLL/SLL treatment options with the Lymphoma Research Foundation. On the topic of future treatments Dr. Furman spoke about the exciting treatment options in the future:

“This is a critical time for treatment in CLL because we are witnessing a change in treatment paradigms. We are for the first time seeing the opportunity to move completely away from a dependence on chemotherapy. These new treatments are highly effective and well tolerated. Three new treatments that have recently been approved include ibrutinib, idelalisib and obinutuzumab. There are also two second-generation BTK inhibitors that work similar to ibrutinib and are well tolerated that are in the pipeline,” Dr. Furman said. Regarding the new agents, Dr. Furman makes it clear. “Not only are they preferable because they are better tolerated but because they are also far more effective. Going forward, there is an eye toward not only short term toxicities, but also long- term health. As we continue to identify new agents, the possibility of living a long and full life with minimal toxicity is real for CLL/SLL patients, which is exciting.”

The new treatments for CLL/SLL are currently open in clinical trials. You can follow the link to our clinical trials website to see which trials are available for CLL/SLL.

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