Oki Y et al. Proc ASH 2013;Abstract 252.

Slides:

Advertisements

Similar presentations

Allogeneic Transplant Following Brentuximab Vedotin Treatment in Patients with Relapsed or Refractory CD30+ Lymphomas Illidge T et al. Proc ASH 2011;Abstract.

Advertisements

Gopal AK et al. Proc ASH 2013;Abstract 4382.

Moskowitz CH et al. Proc ASH 2014;Abstract 290.

Brown JR et al. Proc ASH 2013;Abstract 523.

Phase 1/2 Study of Weekly MLN9708, an Investigational Oral Proteasome Inhibitor, in Combination with Lenalidomide and Dexamethasone in Patients with Previously.

1Coiffier B et al. Proc ASH 2010;Abstract 114.

Novel AKT Inhibitor Afuresertib in Combination with Bortezomib and Dexamethasone Demonstrates Favorable Safety Profile and Significant Clinical Activity.

Richardson PG et al. Proc ASH 2013;Abstract 535.

Palumbo A et al. Proc ASH 2012;Abstract 446.

Carfilzomib: High Single-Agent Response Rate with Minimal Neuropathy Even in High-Risk Patients 1 Baseline Peripheral Neuropathy Does Not Impact the Efficacy.

LaCasce A et al. Proc ASH 2014;Abstract 293.

Roberts AW et al. Proc ASH 2014;Abstract 325.

Lesokhin AM et al. Proc ASH 2014;Abstract 291.

Results of a Phase II Trial of Brentuximab Vedotin as First Line Salvage Therapy in Relapsed/Refractory HL Prior to AHCT Chen RW et al. Proc ASH 2014;Abstract.

1 Baz R et al. Proc ASH 2014;Abstract Lacy MQ et al.

Efficacy of Denileukin Diftitox Retreatment in Patients with Cutaneous T-Cell Lymphoma Who Relapsed After Initial Response 1 Identification of an Active,

Single-Agent Lenalidomide in Patients with Relapsed/Refractory Mantle Cell Lymphoma Following Bortezomib: Efficacy, Safety and Pharmacokinetics from the.

Treatment with Bendamustine- Bortezomib-Dexamethasone in Relapsed/Refractory Multiple Myeloma Shows Significant Activity and Is Well Tolerated Ludwig H.

Frontline Therapy with Brentuximab Vedotin Combined with ABVD or AVD in Patients with Newly Diagnosed Advanced Stage Hodgkin Lymphoma Younes A et al. Proc.

Weekly MLN9708, an Investigational Oral Proteasome Inhibitor, in Relapsed/Refractory Multiple Myeloma: Results from a Phase I Study After Full Enrollment.

A Phase 2 Study of Elotuzumab in Combination with Lenalidomide and Low-Dose Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: Updated.

Palumbo A et al. Proc ASH 2014;Abstract 175.

Reduced-Intensity Conditioning (RIC) and Allogeneic Stem Cell Transplantation (allo-SCT) for Relapsed/Refractory Hodgkin Lymphoma (HL) in the Brentuximab.

Viardot A et al. Proc ASH 2014;Abstract 4460.

Ibrutinib in Combination with Bendamustine and Rituximab Is Active and Tolerable in Patients with Relapsed/Refractory CLL/SLL: Final Results of a Phase.

A Phase II Study with Carfilzomib, Cyclophosphamide and Dexamethasone (CCd) for Newly Diagnosed Multiple Myeloma Bringhen S et al. Proc ASH 2013;Abstract.

Ibrutinib, Single Agent or in Combination with Dexamethasone, in Patients with Relapsed or Relapsed/Refractory Multiple Myeloma (MM): Preliminary Phase.

Ruan J et al. Proc ASH 2013;Abstract 247.

Lenalidomide Is Safe and Active in Waldenstrom Macroglobulinemia (WM) 1 Updated Results from a Multicenter, Open-Label, Dose-Escalation Phase 1b/2 Study.

Updated Results of a Phase I First-in-Human Study of the BCL-2 Inhibitor ABT-199 (GDC-0199) in Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic.

Rituximab plus Lenalidomide Improves the Complete Remission Rate in Comparison with Rituximab Monotherapy in Untreated Follicular Lymphoma Patients in.

Locatelli F et al. Proc ASH 2013;Abstract 4378.

Maintenance Therapy with Bortezomib plus Thalidomide (VT) or Bortezomib plus Prednisone (VP) in Elderly Myeloma Patients Included in the GEM2005MAS65 Spanish.

Brentuximab Vedotin Administered Concurrently with Multi-Agent Chemotherapy as Frontline Treatment of ALCL and Other CD30-Positive Mature T-Cell and NK-Cell.

A Phase 1 Study of the Selective Phosphatidylinositol 3-Kinase-Delta (PI3Kδ) Inhibitor, Idelalisib (GS- 1101) in Combination with Rituximab and/or Bendamustine.

A Phase 2 Study of Single-Agent Brentuximab Vedotin for Front- Line Therapy of Hodgkin Lymphoma in Patients Age 60 Years and Above: Interim Results Yasenchak.

Bortezomib (BTZ) and Panobinostat (PAN) Combination Is Effective in Patients with Relapsed/Refractory Peripheral T-Cell Lymphoma (PTCL) or NK/T-Cell Lymphoma.

A Multi-Center Phase I/II Trial of Carfilzomib and Pomalidomide with Dexamethasone (Car-Pom-d) in Patients with Relapsed/Refractory Multiple Myeloma Shah.

An Open-Label, Randomized Study of Bendamustine and Rituximab (BR) Compared with Rituximab, Cyclophosphamide, Vincristine, and Prednisone (R-CVP) or Rituximab,

Moskowitz CH et al. Proc ASH 2014;Abstract 673.

Phase II Trial of R-CHOP plus Bortezomib Induction Therapy Followed by Bortezomib Maintenance for Previously Untreated Mantle Cell Lymphoma: SWOG 0601.

Phase II Multicenter Study of Single-Agent Lenalidomide in Subjects with Mantle Cell Lymphoma Who Relapsed or Progressed After or Were Refractory to Bortezomib:

VANTAGE 095: An International, Multicenter, Open-Label Study of Vorinostat (MK-0683) in Combination with Bortezomib in Patients with Relapsed or Refractory.

Brentuximab Vedotin in Combination with RCHOP as Front-Line Therapy in Patients with DLBCL: Interim Results from a Phase 2 Study Yasenchak CA et al. Proc.

MM-005: A Phase 1, Multicenter, Open-Label, Dose-Escalation Study to Determine the Maximum Tolerated Dose for the Combination of Pomalidomide, Bortezomib,

Romidepsin in Association with CHOP in Patients with Peripheral T-Cell Lymphoma: Final Results of the Phase Ib/II Ro-CHOP Study Dupuis J et al. Proc ASH.

Geisler C et al. Proc ASH 2011;Abstract 290.

Moskowitz CH et al. Proc ASH 2015;Abstract 182.

Palumbo A et al. Proc ASH 2012;Abstract 200.

Korde N et al. Proc ASH 2012;Abstract 732.

Shustov AR et al. Proc ASH 2010;Abstract 961.

Gajria D et al. Proc SABCS 2010;Abstract P

Nivolumab in Patients (Pts) with Relapsed or Refractory Classical Hodgkin Lymphoma (R/R cHL): Clinical Outcomes from Extended Follow-up of a Phase 1 Study.

Randomized, Open-Label Phase 1/2 Study of Pomalidomide Alone or in Combination with Low-Dose Dexamethasone in Patients with Relapsed and Refractory Multiple.

Vahdat L et al. Proc SABCS 2012;Abstract P

KEYNOTE-087: Pembrolizumab in Patients With Relapsed/Refractory Classical Hodgkin Lymphoma New Findings in Hematology: Independent Conference Coverage.

Fujiwara H et al. Proc ASH 2015;Abstract 181.

Dunleavy K et al. Proc ASH 2015;Abstract 472.

Dimopoulos MA et al. Proc ASH 2012;Abstract LBA-6.

Fowler NH et al. Proc ASCO 2010;Abstract 8036.

Ferrajoli A et al. Proc ASH 2010;Abstract 1395.

Jakubowiak AJ et al. Proc ASH 2010;Abstract 862.

Coiffier B et al. Proc ASH 2010;Abstract 857.

Ansell SM et al. Proc ASH 2012;Abstract 798.

Seymour JF et al. Proc ASH 2013;Abstract 872.

Forero-Torres A et al. Proc ASH 2011;Abstract 3711.

Zaja F et al. Proc ASH 2010;Abstract 966.

Ahmadi T et al. Proc ASH 2011;Abstract 266.

Advani RH et al. Proc ASH 2011;Abstract 443.

Presentation transcript:

Oki Y et al. Proc ASH 2013;Abstract 252. A Phase I Study of Panobinostat in Combination with ICE (Ifosfamide, Carboplatin and Etoposide) in Patients with Relapsed or Refractory Classical Hodgkin Lymphoma (cHL) Oki Y et al. Proc ASH 2013;Abstract 252.

Background The standard approach for refractory or recurrent cHL is treatment with an effective salvage chemotherapy followed by stem cell transplantation. The commonly used regimen ICE produces complete response (CR) rates ranging from 26% (response evaluation by CT) to approximately 61% (with augmented ICE; response evaluation by PET) (Blood 2001;97:616; 2012;119:1665). Panobinostat, a potent oral pan-deacetylase inhibitor, has shown activity in relapsed/refractory cHL after transplant with an acceptable toxicity profile (JCO 2012;30:2197). Study objective: To evaluate the efficacy and safety of panobinostat in combination with ICE for relapsed/refractory cHL. Oki Y et al. Proc ASH 2013;Abstract 252.

Phase I Study Design — Schedule A Panobinostat Three times a week (M/W/F) Start 1 week prior to ICE Initial dose 20 mg po (M/W/F) Escalate to 30 mg po (M/W/F) ICE Ifosfamide 5 g/m2 on day 1 Carboplatin AUC 5 on day 1 Etoposide 100 mg/m2 on days 1-3 Oki Y et al. Proc ASH 2013;Abstract 252.

Phase I Study Design — Schedule B Panobinostat Three times a week (M/W/F) Start 1 week prior to ICE 30 mg po (M/W/F) ICE Ifosfamide 5 g/m2 on day 1 Carboplatin AUC 5 on day 1 Etoposide 100 mg/m2 on days 1-3 Oki Y et al. Proc ASH 2013;Abstract 252.

Eligibility and Cohorts Eligibility: Relapsed/refractory cHL after front-line anthracycline-containing regimen 21 patients evaluable (25 patients treated) Primary refractory disease (n = 9) Primary endpoint: Determination of the recommended Phase II dose of panobinostat (maximum tolerated dose and different dosing schedules) Secondary endpoints: Toxicity, response rate Cohort assignment Cohort 1 (schedule A): 20 mg, 12 doses (n = 6, dose-limiting toxicity [DLT] in 1) Cohort 2 (schedule A): 30 mg, 12 doses (n = 3, no DLT) Expansion cohort (schedule A): 30 mg, 12 doses (n = 10) Expansion cohort (schedule B): 30 mg, 9 doses (n = 6, 4 patients under treatment not included in analysis) Oki Y et al. Proc ASH 2013;Abstract 252.

Response n = 21 Response With permission from Oki Y et al. Proc ASH 2013;Abstract 252.

Subsequent Treatment 17 responding patients received autologous stem cell transplant without additional treatment except mobilization chemotherapy. 3 patients received one or more additional therapies followed by autologous stem cell transplant. All 20 patients had successful harvest and engraftment. Oki Y et al. Proc ASH 2013;Abstract 252.

% of Patients with Events Adverse Events (N = 21) % of Patients with Events No Grade 3-4 nonhematologic toxicity Grade 4 thrombocytopenia: 84% (schedule A); 50% (schedule B) No deaths With permission from Oki Y et al. Proc ASH 2013;Abstract 252.

Author Conclusions Panobinostat with ICE as a salvage treatment for cHL has acceptable toxicity and promising efficacy, with a CR rate of 71%. An alternative schedule (schedule B) is currently accruing patients. Oki Y et al. Proc ASH 2013;Abstract 252.

Investigator Commentary: Phase I Study of Panobinostat with ICE in Relapsed/Refractory cHL Panobinostat emerged around the same time as brentuximab vedotin as a promising agent for relapsed/refractory HL. Early evidence suggested activity of HDAC inhibitors, in particular panobinostat, in patients with HL. However, although brentuximab vedotin received FDA approval and is now incorporated into therapy for relapsed/refractory HL, panobinostat has not been approved. This Phase I study employed a 3 + 3 design to identify the dose of panobinostat that could be used safely in combination with standard ICE chemotherapy as a salvage regimen for relapsed/refractory HL. With the combination, fatigue was a frequent side effect in 43% of patients, as reported in other studies with HDAC inhibitors. (Continued)

Nausea and vomiting occurred in 43% and 29% of the patients, respectively. Some hematologic toxicities were also observed, as would be expected with the ICE regimen. The overall response rate of 86% and complete response rate of 71% with panobinostat/ICE are higher than what might be anticipated with ICE therapy alone. However, further randomized studies comparing the combination to ICE alone as a salvage regimen are needed before definitive conclusions can be made. Interview with Christopher Flowers, MD, MS, February 24, 2014