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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02605694
• Other study ID #: IPI-145-21
• Secondary ID: 2015-004729-15
• Status: Withdrawn
• Phase: Phase 2
• Start date: December 2015
• Est. completion date: November 2016

Study information

• Verified date: March 2021
• Source: SecuraBio
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: November 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 ß human chorionic gonadotropin (ßhCG) 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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Follicular

Intervention

Drug:
• 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
• Rituximab
375 mg/m2 will be administered as an intravenous (IV) infusion on Day 1 of Cycles 1-6 (21-day cycles).
• R-CHOP
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)
• Prednisone
100 mg orally on Days 1-5 of Cycles 1-6 (21-day cycles)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
SecuraBio

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Complete Response Rate (CRR)	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.
Secondary	Overall Response Rate (ORR)	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.
Secondary	Overall Survival		Every 6 months until the primary analysis for PFS or 3 years from randomization, whichever occurs later.
Secondary	Safety (Treatment Emergent Adverse Events (TEAEs) and changes in safety laboratory values as assessed by NCI-CTCAE, version 4.03)	Adverse events (AEs) and abnormal laboratory values	Continuous from informed consent until 30 days from last dose
Secondary	Pharmacokinetics: Evaluate the Duvelisib concentration in plasma sample	Evaluate the Duvelisib concentration in plasma sample	Cycle 1 Day 15, Cycle 2 Day 1 and 15 (Cycles 1-6 are 21-day cycles)
Secondary	Duration of Response	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.
Secondary	Pharmacokinetics: Evaluate IPI-656 (metabolite) concentration in plasma sample	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)