Duvelisib With Rituximab vs R-CHOP in Subjects With Relapsed/Refractory Follicular Lymphoma (FRESCO)

March 15, 2021 updated by: SecuraBio

A Phase 2, Randomized Study of Duvelisib Administered in Combination With Rituximab vs R-CHOP in Subjects With Relapsed/Refractory Follicular Lymphoma (FRESCO)

Phase II study to evaluate the efficacy and safety of DR vs R-CHOP in subjects with relapsed/refractory FL

Study Overview

Status

Withdrawn

Conditions

Detailed Description

This is a phase 2, randomized, two-arm, open-label study designed to evaluate the efficacy and safety of Duvelisib Administered in Combination with Rituximab vs R-CHOP in Subjects with Relapsed/Refractory Follicular Lymphoma.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Diagnosis of FL: Grade 1, 2, or 3a
  2. Progressed within 24 months of initiating an alkylator-based chemotherapy regimen given as either first- or second-line therapy; single-agent chlorambucil therapy does not fulfill this requirement Note: subjects must have received at least 2 cycles of alkylator-based chemotherapy to be eligible
  3. Previously received rituximab, either as single agent or as part of any combination regimen, and also meet one of the following requirements:

    1. Progressed within 24 months of initiating alkylator-based chemotherapy in the first line and received no additional anticancer therapy
    2. Progressed within 24 months of initiating alkylator-based chemotherapy in the first line and subsequently progressed within 24 months of receiving any second-line treatment and received no additional anticancer therapy
    3. Progressed within 24 months of initiating alkylator-based chemotherapy in the second line and received no additional anticancer therapy
  4. Appropriate to receive R-CHOP
  5. 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)
  6. Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (corresponds to Karnofsky Performance Status [(KPS) ≥60%])
  7. For women of childbearing potential (WCBP): negative serum β human chorionic gonadotropin (βhCG) pregnancy test within 1 week before first treatment (WCBP defined as a sexually mature woman who has not undergone surgical sterilization or who has not been naturally post-menopausal for at least 12 consecutive months for women >55 years of age)

Exclusion Criteria:

  1. Clinical evidence of transformation to a more aggressive subtype of lymphoma or grade 3B FL
  2. Received ≥ 3 previous anticancer regimens prior to enrollment
  3. Received prior R-CHOP therapy
  4. Previous receipt of any anthracycline
  5. Contraindication to any of the individual components of CHOP (cyclophosphamide, vincristine, doxorubicin and prednisone) Severe allergic or anaphylactic reaction to any monoclonal antibody therapy, murine protein, or known hypersensitivity to any of the study drugs
  6. Received prior allogeneic transplant
  7. Received prior treatment with a phosphoinositide-3-kinase (PI3K) inhibitor
  8. History of tuberculosis treatment within the two years prior to randomization
  9. History of chronic liver disease, veno-occlusive disease, alcohol abuse
  10. Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine) or systemic steroids >20 mg of prednisone (or equivalent) QD
  11. Ongoing treatment for systemic bacterial, fungal, or viral infection at screening
  12. Concurrent administration of medications or foods that are strong inhibitors or inducers of cytochrome P450 3A (CYP3A)
  13. Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), or herpes zoster (VZV) at screening
  14. Concurrent active malignancy other than nonmelanoma skin cancer, carcinoma in situ of the cervix
  15. History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or a pacemaker within the last 6 months prior to screening

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Arm 1
Duvelisib 25 mg will be administered orally twice daily (BID) during 21-day cycles (Cycles 1-6) followed by 28-day cycles (Cycle 7 and beyond) until disease progression or unacceptable toxicity; and Rituximab (375 mg/m2) will be administered as an intravenous (IV) infusion on Day 1 of Cycles 1-6 (21-day cycles).
25 mg will be administered orally twice daily (BID) during 21-day cycles (Cycles 1-6) followed by 28-day cycles (Cycle 7 and beyond) until disease progression or unacceptable toxicity
Other Names:
  • IPI-145
375 mg/m2 will be administered as an intravenous (IV) infusion on Day 1 of Cycles 1-6 (21-day cycles).
Other Names:
  • Rituxan
  • MabThera
Active Comparator: Arm 2

R-CHOP will be administered as follows:

IV infusion on Day 1 of Cycles 1-6 (21-day cycles)

  • Cyclophosphamide (750 mg/m2)
  • Doxorubicin hydrochloride (50 mg/m2)
  • Vincristine sulfate (1.4 mg/m2) (2 mg maximum)
  • Rituximab (375 mg/m2) Orally on Days 1-5 of Cycles 1-6 (21-day cycles)
  • Prednisone (100 mg) will be administered.
375 mg/m2 will be administered as an intravenous (IV) infusion on Day 1 of Cycles 1-6 (21-day cycles).
Other Names:
  • Rituxan
  • MabThera

IV infusion on Day 1 of Cycles 1-6 (21-day cycles)

  • Cyclophosphamide (750 mg/m2)
  • Doxorubicin hydrochloride (50 mg/m2)
  • Vincristine sulfate (1.4 mg/m2) (2 mg maximum)
  • Rituximab (375 mg/m2)
Other Names:
  • Rituximab
  • CHOP
100 mg orally on Days 1-5 of Cycles 1-6 (21-day cycles)
Other Names:
  • Deltasone

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression Free Survival (PFS)
Time Frame: Time from randomization to documented disease progression, or death due to any cause, whatever comes first, assessed up to approximately 44 months.
Progression Free Survival (PFS), defined according to the revised International Working Group (IWG) criteria as assessed by the Independent Review Committee (IRC)
Time from randomization to documented disease progression, or death due to any cause, whatever comes first, assessed up to approximately 44 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete Response Rate (CRR)
Time Frame: Every 3-6 Cycles (Cycles 1-6 are 21-days; after Cycle 7 are 28-days) from randomization until first documented progression. Subjects will be evaluated for progression or the primary analysis of PFS, whichever occurs first.
Complete Response Rate (CRR) with complete response defined according to the revised IWG criteria as assessed by the IRC
Every 3-6 Cycles (Cycles 1-6 are 21-days; after Cycle 7 are 28-days) from randomization until first documented progression. Subjects will be evaluated for progression or the primary analysis of PFS, whichever occurs first.
Overall Response Rate (ORR)
Time Frame: Every 3-6 Cycles (Cycles 1-6 are 21-days; after Cycle 7 are 28-days) from randomization until first documented progression or the primary analysis of PFS, whichever occurs first.
ORR defined as best response of complete response (CR) or partial response/remission (PR), according to the revised IWG criteria as assessed by the IRC
Every 3-6 Cycles (Cycles 1-6 are 21-days; after Cycle 7 are 28-days) from randomization until first documented progression or the primary analysis of PFS, whichever occurs first.
Overall Survival
Time Frame: Every 6 months until the primary analysis for PFS or 3 years from randomization, whichever occurs later.
Every 6 months until the primary analysis for PFS or 3 years from randomization, whichever occurs later.
Safety (Treatment Emergent Adverse Events (TEAEs) and changes in safety laboratory values as assessed by NCI-CTCAE, version 4.03)
Time Frame: Continuous from informed consent until 30 days from last dose
Adverse events (AEs) and abnormal laboratory values
Continuous from informed consent until 30 days from last dose
Pharmacokinetics: Evaluate the Duvelisib concentration in plasma sample
Time Frame: Cycle 1 Day 15, Cycle 2 Day 1 and 15 (Cycles 1-6 are 21-day cycles)
Evaluate the Duvelisib concentration in plasma sample
Cycle 1 Day 15, Cycle 2 Day 1 and 15 (Cycles 1-6 are 21-day cycles)
Duration of Response
Time Frame: Every 3-6 Cycles (Cycles 1-6 are 21-days; after Cycle 7 are 28-days) from the first documented response to first documented progression or death, whichever occurs first.
DOR defined as the time from the first documented response to the first documentation of progressive disease (PD) according to the revised IWG criteria or death due to any cause (for subjects with CR or PR only)
Every 3-6 Cycles (Cycles 1-6 are 21-days; after Cycle 7 are 28-days) from the first documented response to first documented progression or death, whichever occurs first.
Pharmacokinetics: Evaluate IPI-656 (metabolite) concentration in plasma sample
Time Frame: Cycle 1 Day 15, Cycle 2 Day 1 and 15 (Cycles 1-6 are 21-day cycles)
Evaluate IPI-656 (metabolite) concentration in plasma sample
Cycle 1 Day 15, Cycle 2 Day 1 and 15 (Cycles 1-6 are 21-day cycles)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2015

Primary Completion (Actual)

November 1, 2016

Study Completion (Actual)

November 1, 2016

Study Registration Dates

First Submitted

November 4, 2015

First Submitted That Met QC Criteria

November 13, 2015

First Posted (Estimate)

November 16, 2015

Study Record Updates

Last Update Posted (Actual)

March 17, 2021

Last Update Submitted That Met QC Criteria

March 15, 2021

Last Verified

March 1, 2021

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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