Tag: Non-Hodgkin Lymphoma

ASH 2014 – WCMC Related Abstracts

It has been another productive year for research in the Lymphoma Program at Weill Cornell Medical College. Listed below are the abstracts we were involved in whole or in part to be presented at this year’s 56th Annual Meeting of the American Society of Hematology (ASH).

Look to this space for future updates about developments at ASH 2014.

Anaplastic Large Cell Lymphoma
781 – Convergent Mutations and New Kinase Fusions Lead to Oncogenic STAT3 Activation in Anaplastic Large Cell Lymphoma
1679 – Identification of a New Subclass of ALK Negative Anaplastic Large Cell Lymphoma Expressing Aberrant Levels of ERBB4 Transcripts

CLL/SLL
327 – Efficacy and Safety of Ibrutinib in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia with 17p Deletion: Results from the Phase II RESONATE™-17 Trial
330 – Second Interim Analysis of a Phase 3 Study of Idelalisib (ZYDELIG®) Plus Rituximab (R) for Relapsed Chronic Lymphocytic Leukemia (CLL): Efficacy Analysis in Patient Subpopulations with Del(17p) and Other Adverse Prognostic Factors
1990 – Pattern of Use of Anticoagulation and/or Antiplatelet Agents in Patients with Chronic Lymphocytic Leukemia (CLL) Treated with Single-Agent Ibrutinib Therapy
3316 – Extracellular Nicotinamide Phosphoribosyltransferase (NAMPT) Shapes the CLL Microenvironment Promoting Macrophage M2 Polarization Via a Non-Enzymatic Mechanism
3331 – Updated Efficacy Including Genetic and Clinical Subgroup Analysis and Overall Safety in the Phase 3 RESONATETM Trial of Ibrutinib Versus Ofatumumab in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
4615 – Cancer-Associated Mutations in SF3B1 Exhibit Neomorphic Splicing Activity and Block Erythroid Differentiation
3343 – Long-Term Follow-up of a Phase 1 Trial of Idelalisib (ZYDELIG®) in Combination with Bendamustine (B), Bendamustine/Rituximab (BR), Fludarabine (F), Chlorambucil (Chl), or Chlorambucil/Rituximab (ChlR) in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

DLBCL
59 – Demethylase Activity of Aid during Germinal Center B Cell Maturation Could Contribute to Lymphomagenesis
143 – Akt Activation Confers an Inferior Survival in Patients with Activated B-Cell Subtype of Diffuse Large B-Cell Lymphoma: A Report from the International DLBCL Rituximab-CHOP Consortium Program
567 – BCL6 Mediates a Stress Tolerance Phenotype through Its BTB Domain
864 – Strand-Specific Total RNA Sequencing Establishes the Complete Transcriptome and Alternative Splicing Repertoire in Diffuse Large B Cell Lymphoma
928 – A Virtual B Cell Lymphoma Model to Predict Effective Combination Therapy
1620 – NF-κB Subunit c-Rel Cooperates with Myc and Mutated p53 to Confer Significantly Worse Survival in Patients with Diffuse Large B-Cell Lymphoma: A Report from the International DLBCL Rituximab-CHOP Consortium Program
1692 – Genetic Mechanisms of Immune Escape in Diffuse Large B Cell Lymphoma
1764 – Hsp90 at the Hub of Metabolic Homeostasis in Malignant B Cells
2032 – Whole-Genome Epigenomic Analysis in Multiple Myeloma Reveals DNA Hypermethylation of B-Cell Specific Enhancers
2963 – Mirna-181a expression Lead to Longer Animal Survival and Slower Tumor-Growth Rate in Diffuse Large B-Cell Lymphoma Xenograft Models
3021 – Characterization of DLBCL-Derived Exosomes and Investigation of Their Biological Properties
3091 – Unexpected and Serious Toxicity Observed with Combined Idelalisib, Lenalidomide and Rituximab in Relapsed/Refractory B Cell Lymphomas: Alliance A051201 and A051202
3547 – EBV Microrna Mir-BHRF1-2 Targets PRDM1/Blimp1: Potential Role in EBV Lymphomagenesis
4417 – A Phase 1 Study of the BET-Bromodomain Inhibitor OTX015 in Patients with Non-Leukemic Hematologic Malignancies

Hodgkin Lymphoma
501 – Results of a Phase II Trial of Brentuximab Vedotin As First Line Salvage Therapy in Relapsed/Refractory HL Prior to AHCT
4400 – Circulating Memory T Cells Isolated from Hodgkin Lymphoma Patients Display Evidence of Exhaustion and Chronic Activation

Mantle Cell Lymphoma
625 – Sustained Remission with the Combination Biologic Doublet of Lenalidomide Plus Rituximab As Initial Treatment for Mantle Cell Lymphoma: A Multi-Center Phase II Study Report
2250 – Acquired in Vitro Resistance to Ibrutinib Is Associated with Transcriptional Re-Programming and Sustained Survival Signaling in Waldenströms Macroglobulinemia and Mantle Cell Lymphoma, Independent of BTK Cys481Mutation
3047 – Poor Overall Survival of Patients with Ibrutinib-Resistant Mantle Cell Lymphoma
4453 – Single-Agent Ibrutinib Demonstrates Safety and Durability of Response at 2 Years Follow-up in Patients with Relapsed or Refractory Mantle Cell Lymphoma: Updated Results of an International, Multicenter, Open-Label Phase 2 Study
4461 – Safety Results from the United States Cohort of the Ibrutinib Early Access Treatment Protocol (EAP: MCL4001) in Patients with Relapsed or Refractory Mantle Cell Lymphoma
4471 – Efficacy and Safety of Single-Agent Ibrutinib in Patients with Mantle Cell Lymphoma Who Progressed after Bortezomib Therapy

Marginal Zone Lymphoma
705 – The Coding Genome of Nodal Marginal Zone Lymphoma Reveals Recurrent Molecular Alterations of PTPRD and Other Jak/Stat Signaling Genes

Non-Hodgkin Lymphoma
60 – Protein Arginine Methyltransferase 5 Directly Targets and Epigenetically Silences microRNAs miR33b and miR96 to Support Constitutive Cyclin D1 Activity in Non-Hodgkin’s Lymphoma
3063 – Durable Responses Following Treatment with the PI3K-Delta Inhibitor Idelalisib in Combination with Rituximab, Bendamustine, or Both, in Recurrent Indolent Non-Hodgkin Lymphoma: Phase I/II Results

T-cell Lymphoma
510 – Integrin αvβ3 Transduces Survival and Angiogenic Signals to T Cell Lymphomas and Is a Therapeutic Target
810 – Transcription Regulation Targeting in Peripheral T Cell Lymphomas Induces Apoptosis and Sensitization to BCL2 Inhibitors

Waldenstrom’s Macroglobulinemia
1689 – The Selective Bcl-2 Inhibitor ABT-199 Synergizes with BTK or Proteasome Inhibitors to Induce Potent Cell Death in Preclinical Models of Bortezomib or Ibrutinib-Resistant Waldenströms Macroglobulinemia
2250 – Acquired in Vitro Resistance to Ibrutinib Is Associated with Transcriptional Re-Programming and Sustained Survival Signaling in Waldenströms Macroglobulinemia and Mantle Cell Lymphoma, Independent of BTK Cys481Mutation
3115 – Therapeutic Sensitivity of CD20- Waldenströms Macroglobulinemia Cells Is Determined By Underlying Genomic and Epigenetic Events
3116 – Targeted Disruption of USP14 and UCHL5 with the Novel Deubiquitinase Enzyme (DUB) Inhibitor, VLX1570, Induces Immense Proteotoxicity and Cell Death in Malignant Plasma Cells
3551 – Methylation Patterns in Waldenströms Macroglobulinemia Cells That Are Inherently Resistant or Have Acquired Resistance to Bortezomib, Converge on the TP63 and Cepba Family of Transcription Factors

New Clinical Trial: Efficacy of ACP-196 in Patients with Relapsed or Refractory de Novo Activated B-cell (ABC) Subtype of Diffuse Large B-Cell Lymphoma (DLBCL)

The Weill Cornell Lymphoma Program has recently opened a new clinical trial for men and women with diffuse large B-cell lymphoma. The study sponsor is Acerta Pharma BV, and the principal investigator at Weill Cornell is Dr. Jia Ruan. For more information about the study, please call Amelyn Rodgriguez, RN at (212) 746-1362 or e-mail Amelyn at amr2017@med.cornell.edu.

Key Eligibility

  • Men and women greater than or equal to 18 years of age
  • Confirmed de novo ABC DLBCL, and subjects must have archival tissue available for central pathology review
  • Recurrence of disease after a complete response or progressive disease at the completion of the treatment regimen preceding entry to the study
  • Detailed eligibility will be reviewed when you contact the study team

Study Details

The purpose of this study is to evaluate the pharmacokinetics (PK), pharmacodynamics (PD), safety, and efficacy of ACP-196 in treating subjects relapsed or refractory de novo ABC diffuse large B-cell lymphoma (DLBCL).

Clinical Studies have shown that targeting the B-cell receptor (BCR) signaling pathway by inhibiting Bruton tyrosine kinase (Btk) produces significant clinical benefit in patients with non-Hodgkin lymphoma. Acerta Pharma BV has developed a novel second generation Btk inhibitor, ACP-196, that achieves significant oral bioavailability and potency.

Treatment Plans

This study is a multi-center, open-label, randomized, parallel group study. No placebo will be administered during this study. Twenty subjects, 10 refractory and 10 relapsed, will be enrolled and will take 100 mg of ACP-196 twice per day.

Treatment will occur for 5 cycles with a 30 day follow-up period following the last dose. Treatment with ACP-196 may be continued for more than 28 days until disease progression or an unacceptable drug-related toxicity occurs. Subjects with disease progression will be removed from the study. All subjects who discontinue study drug will have a safety follow-up visit 30 (±7) days after the last dose of study drug unless they have started another cancer therapy within that time frame.

 

FDA Announces Approval for Beleodaq in Treatment of Peripheral T-cell Lymphoma

Earlier today the US FDA announced the approval of Beleodaq (belinostat) for the treatment of non-Hodgkin lymphoma patients with relapsed or refractory peripheral T-cell lymphoma.  Beleodaq has previously received the FDA orphan product designation due to its utility in treating this rare disease. Beleodaq functions by inhibiting the enzymes that contribute to T-cell growth. During clinical trials:

“The safety and effectiveness of Beleodaq was evaluated in a clinical study involving 129 participants with relapsed or refractory PTCL. All participants were treated with Beleodaq until their disease progressed or side effects became unacceptable. Results showed 25.8 percent of participants had their cancer disappear (complete response) or shrink (partial response) after treatment.”

“The most common side effects seen in Beleodaq-treated participants were nausea, fatigue, fever (pyrexia), low red blood cells (anemia), and vomiting.”

Look to this blog and our clinical trials page for further developments regarding the use of Beleodaq in the treatment of peripheral T-cell lymphoma.