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Study of Duvelisib in Combination With Rituximab vs Rituximab in Subjects With Previously Treated Follicular Lymphoma (DYNAMO + R)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Verastem, Inc.
ClinicalTrials.gov Identifier:
NCT02204982
First received: July 25, 2014
Last updated: February 21, 2017
Last verified: June 2016
  Purpose
A study to evaluate the safety and efficacy of IPI 145 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 Intervention Phase
Follicular Lymphoma
Drug: IPI-145 (duvelisib)
Drug: Placebo
Drug: Rituximab
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Duvelisib in Combination With Rituximab vs Rituximab in Subjects With Previously Treated Follicular Lymphoma

Resource links provided by NLM:


Further study details as provided by Verastem, Inc.:

Primary Outcome Measures:
  • Progression-Free Survival (PFS) [ Time Frame: Until disease progression, for up to 5 years from randomization ]

Secondary Outcome Measures:
  • Overall Response Rate (ORR) [ Time Frame: Until disease progression, for up to 5 years from randomization ]
  • Overall Survival (OS) [ Time Frame: Every 6 months for up to 7 years from randomization ]
  • Duration of Response (DOR) [ Time Frame: Until disease progression, for up to 5 years from randomization ]
  • Treatment- emergent adverse events (TEAEs) and changes in safety laboratory values [ Time Frame: 30 days from last dose ]
  • Plasma concentrations of IPI-145 and its metabolite(s) [ Time Frame: Every 4 weeks for 12 weeks ]

Estimated Enrollment: 400
Study Start Date: September 2014
Estimated Study Completion Date: March 2017
Estimated Primary Completion Date: March 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IPI-145 + Rituximab

IPI-145 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: IPI-145 (duvelisib)
IPI-145 (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:
  • Rituxan
  • MabThera
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:
  • Rituxan
  • MabThera

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 IPI-145 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 IPI-145 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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02204982

Locations
Australia, Victoria
Frankston, Victoria, Australia, 3199
France
Bordeaux, France, 33076
Italy
Bologna, Italy, 40138
Terni, Italy, 05100
Poland
Gdynia, Poland, 81-519
Sponsors and Collaborators
Verastem, Inc.
Investigators
Study Chair: Hagop Youssoufian, MD Verastem, Inc.
  More Information

Responsible Party: Verastem, Inc.
ClinicalTrials.gov Identifier: NCT02204982     History of Changes
Other Study ID Numbers: IPI-145-08
2013-002406-31 ( EudraCT Number )
Study First Received: July 25, 2014
Last Updated: February 21, 2017

Keywords provided by Verastem, Inc.:
Phase 3, Follicular Lymphoma, FL, PI3K

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Rituximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on March 28, 2017