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

NCT02605694 | Withdrawn Phase 2 DMC

• 2 other identifiers: IPI-145-212015-004729-15
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Lymphoma

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  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 Outcomes (7)

• Complete Response Rate (CRR)

  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)

  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

  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)

  Continuous from informed consent until 30 days from last dose

• Pharmacokinetics: Evaluate the Duvelisib concentration in plasma sample

  Cycle 1 Day 15, Cycle 2 Day 1 and 15 (Cycles 1-6 are 21-day cycles)

Study Arms (2)

Arm 1

EXPERIMENTAL

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).

Drug: Duvelisib; Drug: Rituximab

Arm 2

ACTIVE COMPARATOR

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.

Drug: Rituximab; Drug: R-CHOP; Drug: Prednisone

Interventions

Duvelisib DRUG

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

Also known as: IPI-145

Arm 1

Rituximab DRUG

375 mg/m2 will be administered as an intravenous (IV) infusion on Day 1 of Cycles 1-6 (21-day cycles).

Also known as: MabThera, Rituxan

Arm 1; Arm 2

R-CHOP DRUG

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)

Also known as: Rituximab, CHOP

Arm 2

Prednisone DRUG

100 mg orally on Days 1-5 of Cycles 1-6 (21-day cycles)

Also known as: Deltasone

Arm 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of FL: Grade 1, 2, or 3a
• 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
• Previously received rituximab, either as single agent or as part of any combination regimen, and also meet one of the following requirements:
• Progressed within 24 months of initiating alkylator-based chemotherapy in the first line and received no additional anticancer therapy
• 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
• Progressed within 24 months of initiating alkylator-based chemotherapy in the second line and received no additional anticancer therapy
• Appropriate to receive R-CHOP
• 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 ≤2 (corresponds to Karnofsky Performance Status \[(KPS) ≥60%\])
• 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)

You may not qualify if:

• Clinical evidence of transformation to a more aggressive subtype of lymphoma or grade 3B FL
• Received ≥ 3 previous anticancer regimens prior to enrollment
• Received prior R-CHOP therapy
• Previous receipt of any anthracycline
• 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
• Received prior allogeneic transplant
• Received prior treatment with a phosphoinositide-3-kinase (PI3K) inhibitor
• History of tuberculosis treatment within the two years prior to randomization
• History of chronic liver disease, veno-occlusive disease, alcohol abuse
• Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine) or systemic steroids \>20 mg of prednisone (or equivalent) QD
• Ongoing treatment for systemic bacterial, fungal, or viral infection at screening
• Concurrent administration of medications or foods that are strong inhibitors or inducers of cytochrome P450 3A (CYP3A)
• Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), or herpes zoster (VZV) at screening
• Concurrent active malignancy other than nonmelanoma skin cancer, carcinoma in situ of the cervix
• History of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or a pacemaker within the last 6 months prior to screening

Sponsors & Collaborators

• SecuraBio: lead

Study Sites (1)

Unknown Facility

Miami, Florida, 33133, United States

Location

MeSH Terms

Conditions

Lymphoma

Interventions

duvelisib; Rituximab; R-CHOP protocol; Prednisone

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Hagop Youssoufian, MD

  Verastem, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2015
• First Posted: November 16, 2015
• Study Start: December 1, 2015
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: March 17, 2021

Record last verified: 2021-03

Locations

US (1)