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Chronic Lymphocytic LeukemiaPhase 3NCT02004522

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

A Phase 3 study testing Duvelisib and Ofatumumab in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by SecuraBio at 92 sites in 11 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Duvelisib and Ofatumumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
319 participants
Where
92 sitesin 11 countries
Study dates
Nov 2013to Jun 2021
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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%)
Show all 17Show fewer
  • 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
  • Ability to voluntarily sign consent for and adhere to the entire study visit schedule and all protocol requirements
  • Signed and dated institutional review board (IRB)/independent ethics committee (IEC)-approved informed consent form (ICF) before any study specific screening procedures are performed

Who cannot join

  • 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:
Show all 28Show fewer
  • 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)
  • Subjects on antimicrobial, antifungal or antiviral prophylaxis are not specifically excluded if all other inclusion/exclusion criteria are met and there is no evidence of active infection at randomization
  • Human immunodeficiency virus (HIV) infection
  • Prior, current, or chronic hepatitis B or hepatitis C infection
  • History of alcohol abuse or chronic liver disease (other than metastatic disease to the liver)
  • Unable to receive prophylactic treatment for pneumocystis or herpes simplex virus (HSV)
  • Baseline QT interval corrected with Fridericia's method (QTcF) > 480 ms (average of triplicate readings) Note: This criterion does not apply to subjects with a right or left bundle branch block (BBB)
  • Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition), or any important medical illness or abnormal laboratory finding that would, in the investigator's judgment, increase the subject's risk while participating in this study
  • Concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix, bladder, or prostate not requiring treatment. Subjects with previous malignancies are eligible provided that they have been disease free for ≥2 years
  • History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months
  • Administration of medications or foods that are strong inhibitors or inducers of CYP3A within 2 weeks of randomization
  • Prior surgery or gastrointestinal dysfunction that may affect drug absorption (eg, gastric bypass surgery, gastrectomy)
  • Major surgery or invasive intervention within 4 weeks prior to randomization
  • Pregnant or breastfeeding women
  • Hypersensitivity to ofatumumab or its excipients

Trial locations and contacts

92 sites in 11 countries.

92 sites in 11 countries

United States37 sites

  • Study site

    Altamonte Springs, Florida, 32701

  • Study site

    Bonita Springs, Florida, 34135-4529

  • Study site

    Boston, Massachusetts, 02114

  • Study site

    Boston, Massachusetts, 02115

  • Study site

    Bradenton, Florida, 34209

  • Study site

    Brandon, Florida, 33511

  • Study site

    Cape Coral, Florida, 33990

  • Study site

    Charlottesville, Virginia, 22903

  • Study site

    Cincinnati, Ohio, 45236

  • Study site

    Clearwater, Florida, 33761

  • Study site

    Crestview Hills, Kentucky, 41017

  • Study site

    Denver, Colorado, 80218

  • Study site

    Englewood, Florida, 34223

  • Study site

    Fairfield, Ohio, 45014

  • Study site

    Fort Myers, Florida, 33916

  • Study site

    Gainesville, Florida, 32605

  • Study site

    Hackensack, New Jersey, 07601

  • Study site

    Hudson, Florida, 34667

  • Study site

    Inverness, Florida, 34453

  • Study site

    La Jolla, California, 92093-0698

  • Study site

    Largo, Florida, 33777

  • Study site

    Naples, Florida, 34119

  • Study site

    Nashville, Tennessee, 37203

  • Study site

    New Brunswick, New Jersey, 08903

  • Study site

    New Port Richey, Florida, 34655

  • Study site

    New York, New York, 10032

  • Study site

    New York, New York, 10065

  • Study site

    Orange City, Florida, 32763

  • Study site

    Orlando, Florida, 32806

  • Study site

    Port Charlotte, Florida, 33980

  • Study site

    Sarasota, Florida, 34236

  • Study site

    Spring Hill, Florida, 34608

  • Study site

    St Louis, Missouri, 63130

  • Study site

    St. Petersburg, Florida, 33705

  • Study site

    Tampa, Florida, 33607

  • Study site

    Tavares, Florida, 32778

  • Study site

    Venice, Florida, 34292

Other trials in United States

France10 sites

  • Study site

    Argenteuil, 95107

  • Study site

    Bobigny, 93009

  • Study site

    Bordeaux, 33076

  • Study site

    Caen, 14033

  • Study site

    Clermont-Ferrand, 63100

  • Study site

    La Roche-sur-Yon, 85025

  • Study site

    Limoges, 87042

  • Study site

    Nantes, 44000

  • Study site

    Rennes, 35033

  • Study site

    Vendœuvres, 54511

Other trials in France

Italy9 sites

  • Study site

    Catania, 95124

  • Study site

    Lecce, 73100

  • Study site

    Meldola, 47014

  • Study site

    Milan, 20132

  • Study site

    Milan, 20162

  • Study site

    Padova, 35128

  • Study site

    Ravenna, 48121

  • Study site

    Rimini, 47923

  • Study site

    Roma, 00133

Other trials in Italy

Hungary7 sites

  • Study site

    Budapest, 1083

  • Study site

    Budapest, 1122

  • Study site

    Debrecen, 4032

  • Study site

    Győr, 9024

  • Study site

    Kaposvár, 7400

  • Study site

    Pécs, 7624

  • Study site

    Szeged, 6725

Other trials in Hungary

Spain6 sites

  • Study site

    Barcelona, 08035

  • Study site

    Barcelona, 08036

  • Study site

    Barcelona, 08041

  • Study site

    Madrid, 28033

  • Study site

    Madrid, 28050

  • Study site

    Pamplona, 31008

Other trials in Spain

Belgium5 sites

  • Study site

    Brussels, 1000

  • Study site

    Brussels, 1200

  • Study site

    Ghent, 9000

  • Study site

    Leuven, 3000

  • Study site

    Sint-Niklaas, 9100

Other trials in Belgium

Germany5 sites

  • Study site

    Berlin, 10707

  • Study site

    Cologne, 50937

  • Study site

    Leer, 26789

  • Study site

    Rostock, 18057

  • Study site

    Ulm, 89081

Other trials in Germany

United Kingdom5 sites

  • Study site

    Bournemouth, BH7 7DW

  • Study site

    Leeds, LS9 7TF

  • Study site

    Manchester, M20 4BX

  • Study site

    Nottingham, NG5 1PB

  • Study site

    Oxford, OX3 7JL

Other trials in United Kingdom

Australia3 sites

  • Study site

    Bedford Park, 5042

  • Study site

    East Melbourne, 3002

  • Study site

    Melbourne, 3058

Other trials in Australia

Austria3 sites

  • Study site

    Vienna, 1090

  • Study site

    Vienna, 1130

  • Study site

    Wels, 4600

Other trials in Austria

New Zealand2 sites

  • Study site

    Auckland, 1023

  • Study site

    Palmerston North, 4442

Other trials in New Zealand

About this study

Official title: A Phase 3 Study of Duvelisib Versus Ofatumumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma (DUO)

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).

Read the detailed description

This is an open-label, two- arm, randomized phase 3, superiority trial designed to evaluate the efficacy and safety of duvelisib compared to ofatumumab administered to patients who have been diagnosed with CLL/SLL whose disease is relapsed or refractory.

Approximately 150 subjects will receive a starting dose of 25 mg duvelisib BID initially over the course of 21-day treatment cycle followed by 28-day treatment cycles for up to 18 cycles or until disease progression or unacceptable toxicity (whichever comes first). After 18 complete cycles of treatment, subjects may receive additional cycles of duvelisib until disease progression or unacceptable toxicity if they, in the judgment of the Investigator, may derive benefit from continued treatment, and if the subject meets the criteria for additional treatment at Cycle 19 Day 1.

Approximately 150 subjects will receive a starting dose of 300 mg ofatumumab on Day 1 followed by seven weekly doses of 2000 mg. Thereafter, subjects will receive 2000 mg ofatumumab once every month for four months. Administration of ofatumumab will not exceed the 12 doses (within 7 cycles).

Being tested
Duvelisib, Ofatumumab
Keywords
Phase 3, CLL/SLL, Pi3K
Medical subject headings
Leukemia, Lymphocytic, Chronic, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DuvelisibDrug

    Also called Copiktra, IPI-145, PI3K Inhibitor

    PI3K Inhibitor

  • OfatumumabDrug

    Also called Arzerra

    monoclonal antibody

Study groups in NCT02004522
Study groupRoleWhat they receive
DuvelisibExperimentalDuvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules.
Receives: Drug: Duvelisib
OfatumumabActive comparatorOfatumumab 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.
Receives: Drug: Ofatumumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. Overall Response Rate (ORR)

    ORR is a key secondary efficacy endpoint with overall response defined as best response of CR, CRi, PR, or PRwL, according to the modified IWCLL/IWG Response Criteria, with modification for treatment-related lymphocytosis as defined in the protocol.

    Measured: Until disease progression or unacceptable toxicity assessed up to 6 years

  2. Number of Subjects With Hematologic Improvements

    Subjects with hematologic improvement included those subjects with abnormally high values for neutrophil count, hemoglobin, or platelet count at Baseline determined to have consistently met the criteria of an improvement for those parameters for a period of at least 60 days during which the subject did not have a transfusion or exogenous cytokines.

    Measured: 3 years

  3. Overall Survival

    A stratified Cox regression analysis was used to test for any treatment effect.

    Measured: Every 6 months for up to 3 years after first dose

  4. Lymph Node Response Rate

    Lymph node response defined as greater than or equal to 50% decrease in the SPD of target lymph nodes

    Measured: 3 years

  5. Duration of Response (DOR)

    Duration of response is defined only for subjects demonstrating a response (eg, CR, CRi, PR, PRwL), with the response and progression statuses both determined by the blinded, central independent review. The analysis will be descriptive for each treatment group only.

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

  6. Treatment-Emergent Adverse Events (TEAEs) and Changes in Safety Laboratory Values

    An analysis of TEAEs with an onset within the first 24 weeks of treatment was performed to examine and compare the incidence of events across an equal period for each treatment arm.Twenty-four weeks was anticipated to be the median exposure to ofatumumab.

    Measured: From 04 Feb 2014 till 19 June 2018

  7. Number of Subjects With Samples Available for Duvelisib Pharmacokinetics (PK)

    Number of subjects with samples available for duvelisib Pharmacokinetics (PK)

    Measured: Cycle 2, Cycle 3, and Cycle 7

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Dec 2013 (estimated)
  2. Study startNov 2013
  3. Primary completion19 May 2017
  4. Study completionJun 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
319 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02004522
Sponsor's protocol ID
IPI-145-07
Other IDs
2013-002405-61
Status last verified
Sep 2023
First submitted
13 Nov 2013
Last updated
21 Sep 2023
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 30287523

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Duvelisib and Ofatumumab in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by SecuraBio at 92 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 92 sites in United States, France, Italy, Hungary, Spain and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Jan 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival (PFS) (time frame: 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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02004522, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2023.

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