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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT02004522




Registration number
NCT02004522
Ethics application status
Date submitted
13/11/2013
Date registered
9/12/2013
Date last updated
21/09/2023

Titles & IDs
Public title
A Phase 3 Study of Duvelisib Versus Ofatumumab in Patients With Relapsed or Refractory CLL/SLL (DUO)
Scientific title
A Phase 3 Study of Duvelisib Versus Ofatumumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma (DUO)
Secondary ID [1] 0 0
2013-002405-61
Secondary ID [2] 0 0
IPI-145-07
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Lymphocytic Leukemia 0 0
Small Lymphocytic Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Duvelisib
Treatment: Drugs - Ofatumumab

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

Active Comparator: Ofatumumab - 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.


Treatment: Drugs: Duvelisib
PI3K Inhibitor

Treatment: Drugs: Ofatumumab
monoclonal antibody
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS)
Timepoint [1] 0 0
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 outcome [1] 0 0
Overall Response Rate (ORR)
Timepoint [1] 0 0
Until disease progression or unacceptable toxicity assessed up to 6 years
Secondary outcome [2] 0 0
Number of Subjects With Hematologic Improvements
Timepoint [2] 0 0
3 years
Secondary outcome [3] 0 0
Overall Survival
Timepoint [3] 0 0
Every 6 months for up to 3 years after first dose
Secondary outcome [4] 0 0
Lymph Node Response Rate
Timepoint [4] 0 0
3 years
Secondary outcome [5] 0 0
Duration of Response (DOR)
Timepoint [5] 0 0
Time from the first documentation of response to first documentation of progressive disease or death due to any cause
Secondary outcome [6] 0 0
Treatment-Emergent Adverse Events (TEAEs) and Changes in Safety Laboratory Values
Timepoint [6] 0 0
From 04 Feb 2014 till 19 June 2018
Secondary outcome [7] 0 0
Number of Subjects With Samples Available for Duvelisib Pharmacokinetics (PK)
Timepoint [7] 0 0
Cycle 2, Cycle 3, and Cycle 7

Eligibility
Key inclusion criteria
- 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:

1. Serum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) = 3 x
upper limit of normal (ULN)

2. Total bilirubin = 1.5 x ULN

3. Serum creatinine = 2.0 x ULN

4. Hemoglobin = 8.0 g/dL with or without transfusion support

5. Platelet count = 10,000 µL with or without transfusion support

- For women of childbearing potential (WCBP): negative serum ß-human chorionic
gonadotropin (ßhCG) 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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)

- 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/06/2021
Sample size
Target
Accrual to date
Final
319
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Bedford Park
Recruitment hospital [2] 0 0
- East Melbourne
Recruitment hospital [3] 0 0
- Melbourne
Recruitment postcode(s) [1] 0 0
5042 - Bedford Park
Recruitment postcode(s) [2] 0 0
3002 - East Melbourne
Recruitment postcode(s) [3] 0 0
3058 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Kentucky
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Tennessee
Country [11] 0 0
United States of America
State/province [11] 0 0
Virginia
Country [12] 0 0
Austria
State/province [12] 0 0
Vienna
Country [13] 0 0
Austria
State/province [13] 0 0
Wels
Country [14] 0 0
Austria
State/province [14] 0 0
Wien
Country [15] 0 0
Belgium
State/province [15] 0 0
Bruxelles
Country [16] 0 0
Belgium
State/province [16] 0 0
Gent
Country [17] 0 0
Belgium
State/province [17] 0 0
Leuven
Country [18] 0 0
Belgium
State/province [18] 0 0
Sint- Niklaas
Country [19] 0 0
France
State/province [19] 0 0
Argenteuil
Country [20] 0 0
France
State/province [20] 0 0
Bobigny
Country [21] 0 0
France
State/province [21] 0 0
Bordeaux
Country [22] 0 0
France
State/province [22] 0 0
Caen
Country [23] 0 0
France
State/province [23] 0 0
Clermont-Ferrand
Country [24] 0 0
France
State/province [24] 0 0
La Roche Sur Yon
Country [25] 0 0
France
State/province [25] 0 0
Limoges Cedex
Country [26] 0 0
France
State/province [26] 0 0
Nantes
Country [27] 0 0
France
State/province [27] 0 0
Rennes
Country [28] 0 0
France
State/province [28] 0 0
Vendœuvres
Country [29] 0 0
Germany
State/province [29] 0 0
Berlin
Country [30] 0 0
Germany
State/province [30] 0 0
Köln
Country [31] 0 0
Germany
State/province [31] 0 0
Leer
Country [32] 0 0
Germany
State/province [32] 0 0
Rostock
Country [33] 0 0
Germany
State/province [33] 0 0
Ulm
Country [34] 0 0
Hungary
State/province [34] 0 0
Budapest
Country [35] 0 0
Hungary
State/province [35] 0 0
Debrecen
Country [36] 0 0
Hungary
State/province [36] 0 0
Gyor
Country [37] 0 0
Hungary
State/province [37] 0 0
Kaposvár
Country [38] 0 0
Hungary
State/province [38] 0 0
Pecs
Country [39] 0 0
Hungary
State/province [39] 0 0
Szeged
Country [40] 0 0
Italy
State/province [40] 0 0
Catania
Country [41] 0 0
Italy
State/province [41] 0 0
Lecce
Country [42] 0 0
Italy
State/province [42] 0 0
Meldola
Country [43] 0 0
Italy
State/province [43] 0 0
Milano
Country [44] 0 0
Italy
State/province [44] 0 0
Padova
Country [45] 0 0
Italy
State/province [45] 0 0
Ravenna
Country [46] 0 0
Italy
State/province [46] 0 0
Rimini
Country [47] 0 0
Italy
State/province [47] 0 0
Roma
Country [48] 0 0
New Zealand
State/province [48] 0 0
Auckland
Country [49] 0 0
New Zealand
State/province [49] 0 0
Palmerston North
Country [50] 0 0
Spain
State/province [50] 0 0
Barcelona
Country [51] 0 0
Spain
State/province [51] 0 0
Madrid
Country [52] 0 0
Spain
State/province [52] 0 0
Pamplona
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Bournemouth
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Leeds
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Manchester
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Nottingham
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
SecuraBio
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/ct2/show/NCT02004522
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries