A Study of Duvelisib in Participants With Refractory Indolent Non-Hodgkin Lymphoma (DYNAMO)

A Phase 2 Study of Duvelisib in Subjects With Refractory Indolent Non-Hodgkin Lymphoma

This was a Phase 2 clinical trial to evaluate the safety and efficacy of duvelisib as a monotherapy in participants with indolent non-Hodgkin lymphoma (iNHL) (follicular lymphoma [FL], marginal zone lymphoma, or small lymphocytic lymphoma) that was refractory to rituximab and to either chemotherapy or radioimmunotherapy (RIT).

Study Overview

• Status: Completed
• Conditions: Indolent Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: Duvelisib

Detailed Description

This was an open-label, single-arm safety and efficacy study of duvelisib administered orally to participants who had been diagnosed with iNHL whose disease was refractory to rituximab and to either chemotherapy or RIT.

Approximately 120 participants received 25 milligrams of duvelisib twice daily over the course of 28-day treatment cycles for up to 13 cycles.

After completing 13 treatment cycles of duvelisib, participants continued to receive additional cycles of duvelisib until disease progression or unacceptable toxicity. However, to receive additional cycles of duvelisib beyond 13 cycles, participants must have had evidence of response (complete response [CR] or partial response [PR]) or stable disease according to the International Working Group criteria by the end of Cycle 13.

• Study Type: Interventional
• Enrollment (Actual): 129
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belarus
  • Brest, Belarus, 224027
  • Minsk, Belarus, 220013
  • Vitebsk, Belarus, 210603
  • Minsk Region
    • Lesnoy, Minsk Region, Belarus, 223040
• Belgium
  • Gent, Belgium, 9000
  • Kortrijk, Belgium, 8500
• Bulgaria
  • Sofia, Bulgaria, 1756
  • Sofia, Bulgaria, 1233
  • Sofia, Bulgaria, 1431
  • Sofia, Bulgaria, 1407
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
  • Quebec
    • Gatineau, Quebec, Canada, J8P7H2
    • Montreal, Quebec, Canada, H3T 1E2
• Czechia
  • Brno, Czechia, 625-00
  • Ostrava-Poruba, Czechia, 708-52
• France
  • Angers Cedex 09, France, 49933
  • Bordeaux, France, 33076
  • Clermont-Ferrand, France, 63000
  • Marseille, France, 13005
  • Pierre Benite, France, 69495
• Georgia
  • Tbilisi, Georgia, 0186
• Hungary
  • Budapest, Hungary, 1122
  • Budapest, Hungary, 1083
  • Debrecen, Hungary, 4032
• Italy
  • Bologna, Italy, 40138
  • Brescia, Italy, 25123
  • Busto Arsizio, Italy, 21052
  • Genova, Italy, 16132
  • Meldola, Italy, 47014
  • Milano, Italy, 20162
  • Modena, Italy, 41124
  • Orbassano, Italy, 10043
  • Parma, Italy, 43100
  • Ravenna, Italy, 48121
  • Rimini, Italy, 47923
  • Varese, Italy, 21100
• Spain
  • Barcelona, Spain, 08036
  • Madrid, Spain, 28222
  • Salamanca, Spain, 37007
• United Kingdom
  • Cardiff, United Kingdom, CF 14 4XW
  • Chelsea, United Kingdom
  • Liverpool, United Kingdom, L7 8XP
  • London, United Kingdom, NW1 2PG
  • London, United Kingdom, W1G 6AD
  • Sutton, United Kingdom, SM2 5PT
• United States
  • California
    • Los Angeles, California, United States, 90095-6984
    • Whittier, California, United States, 90603
  • Colorado
    • Denver, Colorado, United States, 80218
  • Florida
    • Fort Myers, Florida, United States, 39916
    • Saint Petersburg, Florida, United States, 33705
    • Tallahassee, Florida, United States, 32308
  • Georgia
    • Atlanta, Georgia, United States, 30322
  • Illinois
    • Chicago, Illinois, United States, 60637
  • Kentucky
    • Louisville, Kentucky, United States, 40207
  • Maryland
    • Baltimore, Maryland, United States, 21229
    • Baltimore, Maryland, United States, 21204
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
  • Missouri
    • Saint Louis, Missouri, United States, 63110
  • New Jersey
    • Howell, New Jersey, United States, 07731
    • Morristown, New Jersey, United States, 07962
  • New York
    • New York, New York, United States, 10021
    • Rockville Centre, New York, United States, 11510
  • Ohio
    • Canton, Ohio, United States, 44718
  • Oklahoma
    • Lawton, Oklahoma, United States, 73505
    • Oklahoma City, Oklahoma, United States, 73104
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 01911
  • Tennessee
    • Nashville, Tennessee, United States, 37203
  • Texas
    • Dallas, Texas, United States, 75246
  • Virginia
    • Lynchburg, Virginia, United States, 24501

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Participants who had been diagnosed with iNHL that had progressed.
• Participants must have exhibited lack of CR or progressive disease (PR) or progression within 6 months after the last dose of a chemotherapy induction regimen or RIT.
• Participants must have had rituximab-refractory disease, defined as lack of CR or PR or PD within 6 months of last dose.
• Measurable disease with a lymph node or tumor mass ≥1.5 centimeters in at least one dimension by computed tomography (CT), positron emission tomography/CT or magnetic resonance imaging.
• Adequate renal and hepatic function.

Exclusion Criteria:

• Candidate for potentially curative therapies in the opinion of the investigator.
• Previous treatment with a PI3K inhibitor or Bruton's tyrosine kinase inhibitor.
• Prior history of allogeneic hematopoietic stem cell transplant.
• Prior chemotherapy, cancer immunosuppressive therapy, or other investigational agents within 4 weeks before first dose of study drug.
• Grade 3B FL and/or clinical evidence of transformation to a more aggressive subtype of lymphoma.
• Symptomatic central nervous system NHL.
• Ongoing systemic bacterial, fungal, or viral infections at the time of initiation of study treatment.
• Prior, current, or chronic hepatitis B or hepatitis C infection, positive result for hepatitis C virus antibodies, hepatitis B surface antigen, or hepatitis B core antibodies.
• History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months prior to first dose of study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Duvelisib	Drug: Duvelisib; Phosphoinositide-3-kinase (PI3K) inhibitor; Other Names: IPI-145; Copiktra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	ORR, defined as the total percentage of participants who had a best overall response of either complete response (CR) or partial response (PR), was evaluated locally (investigator's assessment) according to the revised IWG Response Criteria for Malignant Lymphoma. ORR is reported with a 2-sided 95% exact confidence interval.	Every 8-16 weeks while on treatment with duvelisib for up to 72 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-emergent Adverse Events (TEAEs)	An adverse event was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A TEAE was defined as any adverse event that emerged or worsened in the period from the first dose of study treatment to 30 days after the last dose of study treatment. A summary of serious and all other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.	Every 2-8 weeks for up to 73 months
Duration of Response (DOR)	DOR, defined as the time from the first documentation of response to either progressive disease (PD) or death due to any cause, was evaluated locally (investigator's assessment) according to the revised IWG Response Criteria for Malignant Lymphoma.	Every 8-16 weeks for up to 72 months
Progression-free Survival (PFS)	PFS, defined as the time from the first dose of study treatment to the first documentation of either Investigator-assessed PD or death resulting from any cause, was evaluated locally (investigator's assessment) according to the revised IWG Response Criteria for Malignant Lymphoma.	Every 8-16 weeks for up to 72 months
Overall Survival (OS)	OS, defined as the time from the first dose of study treatment to the date of death, was evaluated locally (investigator's assessment) according to the revised IWG Response Criteria for Malignant Lymphoma.	Every 16 weeks for up to 72 months
Plasma Concentration of Duvelisib and IPI-656	The serum concentration of duvelisib and its main metabolite, IPI-656, are reported for Day 15 of Cycle 1 (C1D15) and Day 1 of Cycle 2 (C2D1) and Day 1 of Cycle 3 (C3D1). Results are reported in nanograms/milliliter (ng/mL).	Every 4 weeks for 12 weeks (C1D15: predose, 1 and 4 hours post dose; C2D1 and C3D1: anytime during study visit)
Time to Response (TTR)	TTR, defined as the time from the first dose of study treatment to the first documentation of response, was evaluated by an independent, third-party panel of radiologists and oncologists (Independent Review Committee [IRC]) according to the revised IWG Response Criteria for Malignant Lymphoma.	First dose to first documentation of complete or partial response (up to 6 months)

Collaborators and Investigators

• Sponsor: SecuraBio

Publications and helpful links

General Publications

• Flinn IW, Miller CB, Ardeshna KM, Tetreault S, Assouline SE, Mayer J, Merli M, Lunin SD, Pettitt AR, Nagy Z, Tournilhac O, Abou-Nassar KE, Crump M, Jacobsen ED, de Vos S, Kelly VM, Shi W, Steelman L, Le N, Weaver DT, Lustgarten S, Wagner-Johnston ND, Zinzani PL. DYNAMO: A Phase II Study of Duvelisib (IPI-145) in Patients With Refractory Indolent Non-Hodgkin Lymphoma. J Clin Oncol. 2019 Apr 10;37(11):912-922. doi: 10.1200/JCO.18.00915. Epub 2019 Feb 11. Erratum In: J Clin Oncol. 2019 Jun 1;37(16):1448.

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2013
• Primary Completion (Actual): November 18, 2020
• Study Completion (Actual): November 18, 2020

Study Registration Dates

• First Submitted: May 31, 2013
• First Submitted That Met QC Criteria: June 18, 2013
• First Posted (Estimated): June 20, 2013

Study Record Updates

• Last Update Posted (Actual): September 7, 2023
• Last Update Submitted That Met QC Criteria: September 5, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: PI3K Inhibitor
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: IPI-145-06; 2013-004008-20 (EudraCT Number)