DYNAMO + R: Study of Duvelisib in Combination With Rituximab vs Rituximab in Subjects With Previously Treated Follicular Lymphoma
Study Details
Study Description
Brief Summary
A study to evaluate the safety and efficacy of duvelisib administered in combination with rituximab vs placebo in combination with rituximab in patients with previously treated CD20-positive follicular lymphoma who are not suitable candidates for chemotherapy.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
Detailed Description
Study IPI-145-08 is an international, multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase 3 study designed to evaluate the efficacy and safety of duvelisib in combination with rituximab vs placebo in combination with rituximab in subjects with previously treated CD20-positive follicular lymphoma.
Approximately 400 subjects will receive 25 mg of duvelisib or placebo, orally BID for 28 day continuous cycles, in combination with 375 mg/m2 of Rituximab given once weekly for 4 weeks during Cycle 1 and then once on Day 1 of Cycles 4, 6, 8, and 10. Patients will remain on treatment for up to 27 cycles and may continue treatment if clinical benefit is observed.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Duvelisib + Rituximab Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg. |
Drug: Duvelisib
PI3K Inhibitor
Other Names:
Drug: Rituximab
IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10.
Other Names:
|
Placebo Comparator: Placebo + Rituximab Placebo is administered orally and supplied as formulated capsules to match the active 5 mg and 25 mg capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg. |
Drug: Placebo
Matching Placebo (25 mg BID) administered orally in 28-day continuous treatment cycles.
Drug: Rituximab
IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Progression-Free Survival (PFS) [Until disease progression, for up to 5 years from randomization]
Due to the small number of enrolled subjects and study being terminated, PFS endpoint analysis was not performed.
Secondary Outcome Measures
- Overall Response Rate (ORR) [Until disease progression, for up to 5 years from randomization]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Diagnosis of CD20-positive FL:
-
Histology grades 1, 2 or 3a
-
Biopsy-confirmed histopathological diagnosis of FL. Biopsy specimen should be obtained ≤2 years prior to randomization, unless medically contraindicated
-
CD20 immunophenotyping performed ≤2 years prior to randomization
-
First or subsequent relapse following at least one induction therapy regimen containing rituximab in combination with an anthracycline or rituximab in combination with an alkylating agent
-
Patients in first relapse must be chemoresistant or intolerant to chemotherapy
-
No response or disease progression ≤ 24 months from start of last previous therapy
-
At least 1 measurable disease lesion >1.5 cm in at least one diameter by CT/CT-PET or magnetic resonance imaging (MRI) in an area of no prior radiation therapy, or in an area that was previously irradiated that has documented progression
Exclusion Criteria:
-
Clinical evidence of other indolent forms of lymphoma (e.g., marginal zone lymphoma [MZL], small lymphocytic lymphoma [SLL])
-
Transformation to a more aggressive subtype of lymphoma or grade 3b FL
-
Refractory to rituximab: defined as disease progression while receiving or within 6 months of completing either weekly rituximab induction therapy, or rituximab-based chemoimmunotherapy induction
-
Intolerance to rituximab or severe allergic or anaphylactic reaction to any humanized or murine monoclonal antibodies
-
Prior allogeneic hematopoietic stem cell transplant (HSCT)
-
Known Central Nervous System (CNS) lymphoma; subjects with symptoms of CNS disease must have a negative CT scan and negative diagnostic lumbar puncture
-
Prior treatment with a PI3K inhibitor or BTK inhibitor
-
History of tuberculosis within the preceding two years
-
Ongoing systemic bacterial, fungal, or viral infections at randomization (defined as requiring IV antimicrobial, antifungal or antiviral agents)
-
Subjects on antimicrobial, antifungal or antiviral prophylaxis are not specifically excluded if all other I/E criteria are met
-
Prior, current, or chronic hepatitis B or hepatitis C infection, positive result for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) or hepatitis C virus antibodies (HCV Ab)
-
History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within the last 6 months
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Frankston | Victoria | Australia | 3199 | |
2 | Bordeaux | France | 33076 | ||
3 | Bologna | Italy | 40138 | ||
4 | Terni | Italy | 05100 | ||
5 | Gdynia | Poland | 81-519 |
Sponsors and Collaborators
- SecuraBio
Investigators
- Study Chair: Hagop Youssoufian, MD, Verastem, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- IPI-145-08
- 2013-002406-31
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Duvelisib + Rituximab | Placebo + Rituximab |
---|---|---|
Arm/Group Description | Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg. Duvelisib: duvelisib (25 mg BID) administered orally in 28-day continuous treatment cycles Rituximab: IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10. | Placebo is administered orally and supplied as formulated capsules to match the active 5 mg and 25 mg capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg. Placebo: Matching Placebo (25 mg BID) administered orally in 28-day continuous treatment cycles. Rituximab: IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10. |
Period Title: Overall Study | ||
STARTED | 6 | 7 |
COMPLETED | 2 | 0 |
NOT COMPLETED | 4 | 7 |
Baseline Characteristics
Arm/Group Title | Duvelisib + Rituximab | Placebo + Rituximab | Total |
---|---|---|---|
Arm/Group Description | Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg. Duvelisib: duvelisib (25 mg BID) administered orally in 28-day continuous treatment cycles Rituximab: IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10. | Placebo is administered orally and supplied as formulated capsules to match the active 5 mg and 25 mg capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg. Placebo: Matching Placebo (25 mg BID) administered orally in 28-day continuous treatment cycles. Rituximab: IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10. | Total of all reporting groups |
Overall Participants | 6 | 7 | 13 |
Age (Count of Participants) | |||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
4
66.7%
|
2
28.6%
|
6
46.2%
|
>=65 years |
2
33.3%
|
5
71.4%
|
7
53.8%
|
Age (years) [Median (Inter-Quartile Range) ] | |||
Median (Inter-Quartile Range) [years] |
56.5
|
68
|
68
|
Sex: Female, Male (Count of Participants) | |||
Female |
4
66.7%
|
1
14.3%
|
5
38.5%
|
Male |
2
33.3%
|
6
85.7%
|
8
61.5%
|
Race (NIH/OMB) (Count of Participants) | |||
American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
Asian |
0
0%
|
0
0%
|
0
0%
|
Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
Black or African American |
0
0%
|
1
14.3%
|
1
7.7%
|
White |
5
83.3%
|
5
71.4%
|
10
76.9%
|
More than one race |
1
16.7%
|
0
0%
|
1
7.7%
|
Unknown or Not Reported |
0
0%
|
1
14.3%
|
1
7.7%
|
Region of Enrollment (Count of Participants) | |||
United States |
1
16.7%
|
1
14.3%
|
2
15.4%
|
Australia |
1
16.7%
|
0
0%
|
1
7.7%
|
Italy |
2
33.3%
|
1
14.3%
|
3
23.1%
|
Spain |
1
16.7%
|
1
14.3%
|
2
15.4%
|
Poland |
1
16.7%
|
2
28.6%
|
3
23.1%
|
Canada |
0
0%
|
1
14.3%
|
1
7.7%
|
France |
0
0%
|
1
14.3%
|
1
7.7%
|
Eastern Cooperative Oncology Group Performance Status (Count of Participants) | |||
0=Fully active, no restrictions |
4
66.7%
|
6
85.7%
|
10
76.9%
|
1= Restricted in physically strenuous activity |
2
33.3%
|
1
14.3%
|
3
23.1%
|
2=Ambulatory more than 50% of waking hours |
0
0%
|
0
0%
|
0
0%
|
3=Confined to bed or chair more than 50% of waking |
0
0%
|
0
0%
|
0
0%
|
4=Completely disabled |
0
0%
|
0
0%
|
0
0%
|
5=Dead |
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
Title | Progression-Free Survival (PFS) |
---|---|
Description | Due to the small number of enrolled subjects and study being terminated, PFS endpoint analysis was not performed. |
Time Frame | Until disease progression, for up to 5 years from randomization |
Outcome Measure Data
Analysis Population Description |
---|
Data could not be reported because the study was terminated early and a sufficient number of subjects and events were not available for analysis. |
Arm/Group Title | Duvelisib + Rituximab | Placebo + Rituximab |
---|---|---|
Arm/Group Description | Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg. Duvelisib: duvelisib (25 mg BID) administered orally in 28-day continuous treatment cycles Rituximab: IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10. | Placebo is administered orally and supplied as formulated capsules to match the active 5 mg and 25 mg capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg. Placebo: Matching Placebo (25 mg BID) administered orally in 28-day continuous treatment cycles. Rituximab: IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10. |
Measure Participants | 0 | 0 |
Title | Overall Response Rate (ORR) |
---|---|
Description | |
Time Frame | Until disease progression, for up to 5 years from randomization |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | Duvelisib + Rituximab | Placebo + Rituximab |
---|---|---|
Arm/Group Description | Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg. Duvelisib: duvelisib (25 mg BID) administered orally in 28-day continuous treatment cycles Rituximab: IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10. | Placebo is administered orally and supplied as formulated capsules to match the active 5 mg and 25 mg capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg. Placebo: Matching Placebo (25 mg BID) administered orally in 28-day continuous treatment cycles. Rituximab: IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10. |
Measure Participants | 5 | 6 |
Complete Response |
3
50%
|
0
0%
|
Partial Response |
2
33.3%
|
1
14.3%
|
Stable Disease |
0
0%
|
3
42.9%
|
Progressive Disease |
0
0%
|
2
28.6%
|
Adverse Events
Time Frame | 15 months | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | Duvelisib + Rituximab | Placebo + Rituximab | ||
Arm/Group Description | Duvelisib is administered orally and supplied as 5 mg and 25 mg formulated capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg. Duvelisib: duvelisib (25 mg BID) administered orally in 28-day continuous treatment cycles Rituximab: IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10. | Placebo is administered orally and supplied as formulated capsules to match the active 5 mg and 25 mg capsules. Rituximab is administered as an intravenous (IV) infusion and is supplied in single-use vials at two strengths, 100 mg and 500 mg. Placebo: Matching Placebo (25 mg BID) administered orally in 28-day continuous treatment cycles. Rituximab: IV infusion of rituximab (375 mg/m2) once weekly for 4 weeks during Cycle 1, then once on Day 1 of Cycles 4, 6, 8, and 10. | ||
All Cause Mortality |
||||
Duvelisib + Rituximab | Placebo + Rituximab | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/6 (0%) | 0/7 (0%) | ||
Serious Adverse Events |
||||
Duvelisib + Rituximab | Placebo + Rituximab | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 5/6 (83.3%) | 0/7 (0%) | ||
Gastrointestinal disorders | ||||
Gastrointestinal Inflammation | 1/6 (16.7%) | 0/7 (0%) | ||
General disorders | ||||
Pyrexia | 1/6 (16.7%) | 0/7 (0%) | ||
Infections and infestations | ||||
Pneumonia | 2/6 (33.3%) | 0/7 (0%) | ||
Pneumonia Cytomegaloviral | 1/6 (16.7%) | 0/7 (0%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Interstitial Lung Disease | 2/6 (33.3%) | 0/7 (0%) | ||
Chronic Obstructive pulmonary disease | 1/6 (16.7%) | 0/7 (0%) | ||
Respiratory Failure | 1/6 (16.7%) | 0/7 (0%) | ||
Pneumonitis | 1/6 (16.7%) | 0/7 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
Duvelisib + Rituximab | Placebo + Rituximab | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 6/6 (100%) | 7/7 (100%) | ||
Blood and lymphatic system disorders | ||||
Neutropenia | 2/6 (33.3%) | 0/7 (0%) | ||
Eye disorders | ||||
Vision blurred | 0/6 (0%) | 1/7 (14.3%) | ||
Gastrointestinal disorders | ||||
Abdominal pain upper | 1/6 (16.7%) | 0/7 (0%) | ||
Constipation | 1/6 (16.7%) | 0/7 (0%) | ||
Diarrhoea | 1/6 (16.7%) | 1/7 (14.3%) | ||
Dysphagia | 1/6 (16.7%) | 0/7 (0%) | ||
Gastrointestinal Inflammation | 1/6 (16.7%) | 0/7 (0%) | ||
Mouth Ulceration | 1/6 (16.7%) | 0/7 (0%) | ||
Nausea | 1/6 (16.7%) | 0/7 (0%) | ||
Abdominal distension | 0/6 (0%) | 1/7 (14.3%) | ||
Dry mouth | 0/6 (0%) | 1/7 (14.3%) | ||
General disorders | ||||
Asthenia | 2/6 (33.3%) | 2/7 (28.6%) | ||
Chest pain | 1/6 (16.7%) | 0/7 (0%) | ||
Oedema peripheral | 1/6 (16.7%) | 1/7 (14.3%) | ||
Pyrexia | 1/6 (16.7%) | 1/7 (14.3%) | ||
Chills | 0/6 (0%) | 2/7 (28.6%) | ||
Fatigue | 0/6 (0%) | 2/7 (28.6%) | ||
Influenza like illness | 0/6 (0%) | 1/7 (14.3%) | ||
Infections and infestations | ||||
Gastroenteritis | 1/6 (16.7%) | 1/7 (14.3%) | ||
Bronchitis | 0/6 (0%) | 1/7 (14.3%) | ||
Bronchitis viral | 0/6 (0%) | 1/7 (14.3%) | ||
Nasopharyngitis | 0/6 (0%) | 1/7 (14.3%) | ||
Oral herpes | 0/6 (0%) | 1/7 (14.3%) | ||
Upper respiratory tract infection | 0/6 (0%) | 2/7 (28.6%) | ||
Injury, poisoning and procedural complications | ||||
Infusion related reaction | 0/6 (0%) | 2/7 (28.6%) | ||
Investigations | ||||
Alanine aminotransferase increased | 3/6 (50%) | 0/7 (0%) | ||
Aspartate aminotransferase increased | 3/6 (50%) | 0/7 (0%) | ||
Amylase increased | 1/6 (16.7%) | 0/7 (0%) | ||
Blood Cholesterol increased | 1/6 (16.7%) | 0/7 (0%) | ||
Gamma-glutamyltransferase increased | 1/6 (16.7%) | 0/7 (0%) | ||
Lipase increased | 1/6 (16.7%) | 0/7 (0%) | ||
Weight increased | 1/6 (16.7%) | 0/7 (0%) | ||
Blood Uric acid increased | 0/6 (0%) | 1/7 (14.3%) | ||
Metabolism and nutrition disorders | ||||
Hyperglycaemia | 1/6 (16.7%) | 0/7 (0%) | ||
Hypertriglyceridaemia | 1/6 (16.7%) | 0/7 (0%) | ||
Hyperuricaemia | 1/6 (16.7%) | 0/7 (0%) | ||
Hypokalaemia | 1/6 (16.7%) | 0/7 (0%) | ||
Musculoskeletal and connective tissue disorders | ||||
Arthralgia | 0/6 (0%) | 1/7 (14.3%) | ||
Metatarsalgia | 0/6 (0%) | 1/7 (14.3%) | ||
Muscle spasms | 0/6 (0%) | 1/7 (14.3%) | ||
Pain in extremity | 0/6 (0%) | 1/7 (14.3%) | ||
Nervous system disorders | ||||
Dysgeusia | 1/6 (16.7%) | 0/7 (0%) | ||
Hypoaesthesia | 1/6 (16.7%) | 0/7 (0%) | ||
Balance disorder | 0/6 (0%) | 1/7 (14.3%) | ||
Sciatica | 0/6 (0%) | 1/7 (14.3%) | ||
Psychiatric disorders | ||||
Anxiety | 0/6 (0%) | 2/7 (28.6%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Cough | 1/6 (16.7%) | 0/7 (0%) | ||
Dyspnoea | 1/6 (16.7%) | 0/7 (0%) | ||
Hypoventilation | 1/6 (16.7%) | 0/7 (0%) | ||
Interstitial Lung Disease | 1/6 (16.7%) | 0/7 (0%) | ||
Productive cough | 0/6 (0%) | 1/7 (14.3%) | ||
Skin and subcutaneous tissue disorders | ||||
Rash | 1/6 (16.7%) | 0/7 (0%) | ||
Pruritis | 0/6 (0%) | 1/7 (14.3%) | ||
Skin Discolouration | 0/6 (0%) | 1/7 (14.3%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Gloria Patrick |
---|---|
Organization | Verastem, Inc. |
Phone | 1-781-469-1594 |
gpatrick@verastem.com |
- IPI-145-08
- 2013-002406-31