A clinical trial which compares the safety and efficacy of chemotherapy (Rituximab and Bendamustine ) combined with Duvelisib, the study treatment, or a placebo in patients who have previously treated Indolent Non-Hodgkin Lymphoma.

• Register: EUCTR
• Last refreshed on: 8 August 2016
• Main ID: EUCTR2015-004033-28-HU
• Date of registration: 19/01/2016
• Prospective Registration: Yes
• Primary sponsor: Infinity Pharmaceuticals, Inc.
• Public title: A clinical trial which compares the safety and efficacy of chemotherapy (Rituximab and Bendamustine ) combined with Duvelisib, the study treatment, or a placebo in patients who have previously treated Indolent Non-Hodgkin Lymphoma.
• Scientific title: A Phase 3, Randomized, Double-blind Study of Duvelisib Administered in Combination with Rituximab and Bendamustine vs Placebo Administered in Combination with Rituximab and Bendamustine in Subjects with Previously-Treated Indolent Non-Hodgkin Lymphoma
• Date of first enrolment: 04/05/2016
• Target sample size: 600
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-004033-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Australia, Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Costa Rica, Czech Republic, Denmark, Ecuador, Egypt, Estonia, Finland, France, Georgia, Germany, Greece, Guatemala, Hong Kong, Hungary, Israel, Italy, Japan, Korea, Republic of, Latvia, Lebanon, Lithuania, Malaysia, Mexico, Netherlands, New Zealand, Panama, Peru, Philippines, Poland, Portugal, Romania, Russian Federation, Serbia, Singapore, Slovakia, Slovenia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: Mary Kuskin
• Affiliation: Infinity Pharmaceuticals, Inc.

• Name: Mary Kuskin
• Affiliation: Infinity Pharmaceuticals, Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
• = 18 years of age
• Diagnosis of iNHL with one of the following histologic sub-types and grade:
- Follicular lymphoma (FL)Grade 1, 2, or 3a
- Small lymphocytic lymphoma (SLL)
- Marginal zone lymphoma (MZL)( splenic, nodal, or extranodal)
• Have received the following systemic treatments for iNHL:
- an anti-CD20 antibody; and
- chemotherapy
• At least 1 measurable disease lesion > 1.5 cm in at least one dimension by computed tomography (CT)/CT-PET or magnetic resonance imaging (MRI)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 (corresponds to Karnofsky Performance Status [(KPS) =60%])
For full inclusion criteria list, refer to protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 420
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 180

Exclusion criteria:
• Clinical evidence of transformation to a more aggressive subtype of lymphoma or grade 3B FL
• Refractory to BR, defined as:
- Progression of disease while receiving or within 6 months of completing bendamustine + rituximab therapy
• Severe allergic or anaphylactic reaction to any monoclonal antibody therapy, murine protein, or known hypersensitivity to any of the study drugs
• Received prior allogeneic transplant
• Received prior treatment with a phosphoinositide-3-kinase (PI3K) inhibitor
• Infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
• History of tuberculosis treatment within the two years prior to randomization
• History of chronic liver disease, veno-occlusive disease, or alcohol abuse
• Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine) or systemic steroids > 20 mg of prednisone (or equivalent) daily (QD)
• Ongoing treatment for systemic bacterial, fungal, or viral infection at screening
• Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), or herpes zoster (VZV) at screening
• Concurrent active malignancy other than non-melanoma skin cancer, carcinoma in situ of the cervix, or prostate intraepithelial neoplasia
• History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or a pacemaker within the last 6 months prior to screening
For full exclusion criteria list, refer to protocol.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Indolent Non-Hodgkin Lymphoma
MedDRA version: 18.1 Level: HLT Classification code 10029621 Term: Non-Hodgkin's lymphomas unspecified histology indolent System Organ Class: 100000004851

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: Duvelisib
Product Code: IPI-145
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Duvelisib
CAS Number: 1386861-48-9
Current Sponsor code: IPI-145
Other descriptive name: IPI-145
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Product Name: Duvelisib
Product Code: IPI-145
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Duvelisib
CAS Number: 1386861-48-9
Current Sponsor code: IPI-145
Other descriptive name: IPI-145
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Capsule, hard
Route of administration of the placebo: Oral use

Trade Name: MabThera
Product Name: MabThera
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: Levact
Product Name: Levact
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: BENDAMUSTINE HYDROCHLORIDE
CAS Number: 3543-75-7
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2.5-

Primary Outcome(s)

Primary end point(s): Progression-Free Survival (PFS), defined as the time from randomization to documented progressive disease (PD) according to the revised International Working Group (IWG) criteria as assessed by the Independent Review Committee (IRC), or death due to any cause

Secondary Objective: • Evaluate the safety of DBR and PBR in subjects with previously-treated iNHL
• Characterize the pharmacokinetics (PK) of duvelisib when administered with bendamustine and rituximab (BR) in subjects with previously-treated iNHL
Exploratory Objectives:
• Evaluate if pre-treatment biomarkers in tissue can predict clinical efficacy and/or safety of DBR vs PBR in subjects with previously-treated iNHL
• Evaluate Quality of Life (QoL) outcomes in subjects with previously-treated iNHL

Main Objective: Evaluate the efficacy of DBR vs PBR in subjects with previously-treated iNHL

Timepoint(s) of evaluation of this end point: From date of enrollment until the date of first documentation of progression or date of death from any cause, whatever came first, assessed up to 78 months

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: All timeframe are described in section E.5.2
-Complete Response (CRR)
-Overall Response Rate (ORR)
-Overall Survival (OS)
-Duration of Response (DOR)
-Safety (Treatment- emergent adverse events (TEAEs) and changes in safety laboratory values)
-Pharmacokinetics (PK)

Secondary end point(s): -Complete Response (CRR): Time Frame is every 3-6 Cycles (each cycle is 28 days) from date of randomization, until date of first documented progression. Subjects will be evaluated for progression through the primary analysis of the study or 5 years from randomization, whichever is later.
-Overall Response Rate (ORR) : Time Frame is every 3-6 Cycles (each cycle is 28 days) from date of randomization, until date of first documented progression. Subjects will be evaluated for progression through the primary analysis of the study or 5 years from randomization, whichever is later.
-Overall Survival (OS): Time Frame is every 6 months for up to 5 years from date of randomization.
-Duration of Response (DOR): Time Frame is every 3-6 Cycles (each cycle is 28 days) from date of randomization, until date of first documented progression. Subjects will be evaluated for progression through the primary analysis of the study or 5 years from randomization, whichever is later.
-Safety (Treatment- emergent adverse events (TEAEs) and changes in safety laboratory values) :Time Frame is Continuous from informed consent until 30 days from last dose
-Pharmacokinetics (PK): Time Frame is Cycle 1 and Cycle 2 (each cycle is 28 days)] to evaluate the Duvelisib concentration in plasma sample.
-Pharmacokinetics (PK): Time Frame is Cycle 1 and Cycle 2 (each cycle is 28 days)] to evaluate IPI-656 (metabolite) concentration in plasma sample.

Secondary ID(s)

IPI-145-22

NCT02576275

Source(s) of Monetary Support

Infinity Pharmaceuticals, Inc.