A Phase 3 Study of Duvelisib Versus Ofatumumab in Patients With Relapsed or Refractory CLL/SLL (DUO)

NCT02004522 | Completed Phase 3 Results DMC

• 2 other identifiers: IPI-145-072013-002405-61
• Study Type: interventional
• Target: 319
• Locations: 10 countries
• Sites: 89

Brief Summary

A Phase 3 clinical trial to examine the efficacy of duvelisib monotherapy versus ofatumumab monotherapy in subjects with relapsed or refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL).

Conditions

Chronic Lymphocytic Leukemia; Small Lymphocytic Lymphoma

Keywords

Phase 3; CLL/SLL; Pi3K

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS)

  The primary efficacy endpoint for the study was PFS, defined as time from randomization to the first documentation of PD as determined by blinded independent review or death due to any cause.

  From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 3 years

Secondary Outcomes (7)

• Overall Response Rate (ORR)

  Until disease progression or unacceptable toxicity assessed up to 6 years

• Number of Subjects With Hematologic Improvements

  3 years

• Overall Survival

  Every 6 months for up to 3 years after first dose

• Lymph Node Response Rate

  3 years

• Duration of Response (DOR)

  Time from the first documentation of response to first documentation of progressive disease or death due to any cause

Study Arms (2)

Duvelisib

EXPERIMENTAL

Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules.

Drug: Duvelisib

Ofatumumab

ACTIVE COMPARATOR

Ofatumumab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg/5 mL and 1000 mg/50 mL.

Drug: Ofatumumab

Interventions

Duvelisib DRUG

PI3K Inhibitor

Also known as: Copiktra, IPI-145, PI3K Inhibitor

Duvelisib

Ofatumumab DRUG

monoclonal antibody

Also known as: Arzerra

Ofatumumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of active CLL or SLL that meets at least one of the IWCLL 2008 criteria for requiring treatment (Binet Stage ≥ B and/or Rai Stage ≥ I)
• Disease that has progressed during or relapsed after at least one previous CLL/SLL therapy
• Not appropriate for treatment with a purine-based analogue regimen (per National Comprehensive Cancer Network \[NCCN\] or European Society for Medical Oncology \[ESMO\] guidelines), including relapse ≤ 36 months from a purine-based chemoimmunotherapy regimen or relapse ≤ 24 months from a purine-based monotherapy regimen
• A cytogenetics or fluorescence in situ hybridization (FISH) analysis of the leukemic cells within 24 months of randomization is required to document the presence or absence of del(17p). Note: if a sample from within 24 months is not available, it should be evaluated as part of the screening laboratory evaluation to inform stratification
• Measurable disease with a lymph node or tumor mass \> 1.5 cm in at least one dimension as assessed by computed tomography (CT)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (corresponds to Karnofsky Performance Status \[KPS\] ≥ 60%)
• Willingness by subject to be randomized to receive either ofatumumab or duvelisib at the dose and schedule defined in the protocol
• Must meet the following laboratory parameters:
• Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≤ 3 x upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 x ULN
• Serum creatinine ≤ 2.0 x ULN
• Hemoglobin ≥ 8.0 g/dL with or without transfusion support
• Platelet count ≥ 10,000 μL with or without transfusion support
• For women of childbearing potential (WCBP): negative serum β-human chorionic gonadotropin (βhCG) pregnancy test within 1 week before randomization (WCBP defined as a sexually mature woman who has not undergone surgical sterilization or who has not been naturally post-menopausal for at least 24 consecutive months \[women ≤ 55 years\] or 12 consecutive months \[women \> 55 years\])
• Willingness of male and female subjects who are not surgically sterile or postmenopausal to use medically acceptable methods of birth control from the first dose of study drug to 30 days after the last dose of duvelisib and for 12 months after last dose of ofatumumab. Sexually active men, and women using oral contraceptive pills, should also use barrier contraception

You may not qualify if:

• History of Richter's transformation or prolymphocytic leukemia
• Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenia purpura (ITP) that is uncontrolled or requiring \> 20 mg once daily (QD) of prednisone (or equivalent) to maintain hemoglobin \> 8.0 g/dL or platelets \> 10,000 μL without transfusion support
• Refractory to ofatumumab (progression or relapse \<12 months of receiving ofatumumab therapy or \<24 months of receiving an ofatumumab- containing regimen)
• Prior allogeneic transplant (prior autologous stem cell transplant \>6 months prior to study entry is permitted)
• Known central nervous system lymphoma or leukemia; subjects with symptoms of CNS disease must have a negative CT scan or negative diagnostic lumbar puncture prior to randomization
• Use of any of the following medications or procedures within the specified timeframe:
• Use of live or live attenuated vaccines within 30 days prior to randomization
• Chemotherapy, radiation therapy, or ablative therapy within 3 weeks of randomization
• Tyrosine kinase inhibitor within 7 days of randomization
• Other investigational therapy (not included above) within 3 weeks of randomization
• Previous treatment with a PI3K inhibitor or BTK inhibitor
• Ongoing treatment with chronic immunosuppressants (eg, cyclosporine) or systemic steroids \> 20 mg prednisone (or equivalent) QD
• History of tuberculosis treatment within the preceding two years
• Ongoing systemic bacterial, fungal, or viral infections at the time of initiation of study treatment (defined as requiring IV antimicrobial, antifungal or antiviral agents)
• Human immunodeficiency virus (HIV) infection

Sponsors & Collaborators

• SecuraBio: lead

Study Sites (92)

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La Jolla, California, 92093-0698, United States

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Denver, Colorado, 80218, United States

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Altamonte Springs, Florida, 32701, United States

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Bonita Springs, Florida, 34135-4529, United States

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Bradenton, Florida, 34209, United States

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Brandon, Florida, 33511, United States

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Cape Coral, Florida, 33990, United States

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Clearwater, Florida, 33761, United States

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Englewood, Florida, 34223, United States

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Fort Myers, Florida, 33916, United States

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Gainesville, Florida, 32605, United States

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Hudson, Florida, 34667, United States

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Inverness, Florida, 34453, United States

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Largo, Florida, 33777, United States

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Naples, Florida, 34119, United States

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New Port Richey, Florida, 34655, United States

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Orange City, Florida, 32763, United States

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Orlando, Florida, 32806, United States

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Port Charlotte, Florida, 33980, United States

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Sarasota, Florida, 34236, United States

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Spring Hill, Florida, 34608, United States

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St. Petersburg, Florida, 33705, United States

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Tampa, Florida, 33607, United States

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Tavares, Florida, 32778, United States

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Venice, Florida, 34292, United States

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Crestview Hills, Kentucky, 41017, United States

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Boston, Massachusetts, 02114, United States

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Boston, Massachusetts, 02115, United States

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St Louis, Missouri, 63130, United States

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Hackensack, New Jersey, 07601, United States

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New Brunswick, New Jersey, 08903, United States

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New York, New York, 10032, United States

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New York, New York, 10065, United States

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Cincinnati, Ohio, 45236, United States

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Fairfield, Ohio, 45014, United States

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Nashville, Tennessee, 37203, United States

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Charlottesville, Virginia, 22903, United States

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Bedford Park, 5042, Australia

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East Melbourne, 3002, Australia

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Melbourne, 3058, Australia

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Vienna, 1090, Austria

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Vienna, 1130, Austria

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Wels, 4600, Austria

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Brussels, 1000, Belgium

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Brussels, 1200, Belgium

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Ghent, 9000, Belgium

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Leuven, 3000, Belgium

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Sint-Niklaas, 9100, Belgium

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Argenteuil, 95107, France

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Bobigny, 93009, France

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Bordeaux, 33076, France

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Caen, 14033, France

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Clermont-Ferrand, 63100, France

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La Roche-sur-Yon, 85025, France

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Limoges, 87042, France

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Nantes, 44000, France

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Rennes, 35033, France

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Vendœuvres, 54511, France

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Berlin, 10707, Germany

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Cologne, 50937, Germany

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Leer, 26789, Germany

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Rostock, 18057, Germany

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Ulm, 89081, Germany

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Budapest, 1083, Hungary

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Budapest, 1122, Hungary

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Debrecen, 4032, Hungary

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Győr, 9024, Hungary

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Kaposvár, 7400, Hungary

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Pécs, 7624, Hungary

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Szeged, 6725, Hungary

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Catania, 95124, Italy

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Lecce, 73100, Italy

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Meldola, 47014, Italy

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Milan, 20132, Italy

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Milan, 20162, Italy

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Padua, 35128, Italy

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Ravenna, 48121, Italy

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Rimini, 47923, Italy

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Roma, 00133, Italy

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Auckland, 1023, New Zealand

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Palmerston North, 4442, New Zealand

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Barcelona, 08035, Spain

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Barcelona, 08036, Spain

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Barcelona, 08041, Spain

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Madrid, 28033, Spain

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Madrid, 28050, Spain

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Pamplona, 31008, Spain

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Bournemouth, BH7 7DW, United Kingdom

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Leeds, LS9 7TF, United Kingdom

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Manchester, M20 4BX, United Kingdom

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Nottingham, NG5 1PB, United Kingdom

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Oxford, OX3 7JL, United Kingdom

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Related Publications (1)

• Flinn IW, Hillmen P, Montillo M, Nagy Z, Illes A, Etienne G, Delgado J, Kuss BJ, Tam CS, Gasztonyi Z, Offner F, Lunin S, Bosch F, Davids MS, Lamanna N, Jaeger U, Ghia P, Cymbalista F, Portell CA, Skarbnik AP, Cashen AF, Weaver DT, Kelly VM, Turnbull B, Stilgenbauer S. The phase 3 DUO trial: duvelisib vs ofatumumab in relapsed and refractory CLL/SLL. Blood. 2018 Dec 6;132(23):2446-2455. doi: 10.1182/blood-2018-05-850461. Epub 2018 Oct 4.

  PMID: 30287523 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

duvelisib; ofatumumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Beth Gregory, PharmD, MBA
• Organization: Secura Bio, Inc.

bgregory@securabio.com

1-702-254-0011

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2013
• First Posted: December 9, 2013
• Study Start: November 1, 2013
• Primary Completion: May 19, 2017
• Study Completion: June 1, 2021
• Last Updated: September 21, 2023
• Results First Posted: January 8, 2019

Record last verified: 2023-09

Locations

AU (3); NZ (2); FR (10); BE (5); IT (9); DE (5); GB (5); ES (6); HU (7); US (37)