A Study of Duvelisib in Patients With Relapsed or Refractory Peripheral T Cell Lymphoma (PTCL)

Sponsor

SecuraBio (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT03372057

Collaborator

(none)

120

Enrollment

Locations

Arms

62.2

Anticipated Duration (Months)

4.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a multi-center, parallel cohort, open-label, Phase 2 study of duvelisib, an oral dual inhibitor of PI3K-δ,γ, in patients with relapsed or refractory Peripheral T cell Lymphoma (PTCL).

Condition or Disease	Intervention/Treatment	Phase
Peripheral T-cell Lymphoma	Drug: Duvelisib Drug: Duvelisib Drug: Duvelisib	Phase 2

Detailed Description

The study has 2 phases, a Dose Optimization Phase and an Expansion Phase.

In the Dose Optimization Phase, patients will be randomly assigned to 1 of 2 study cohorts, as follows:

Cohort 1: Duvelisib PO BID at a starting dose of 25 mg, with potential escalation on a per-patient basis to 50 mg and then 75 mg, based on the patient's response to and tolerance of therapy, in 28-day cycles.
Cohort 2: Duvelisib 75 mg PO BID, administered in 28-day cycles .

A total of 20 patients will be enrolled in the Dose Optimization Phase, with 10 patients per cohort. Based on the safety and activity data obtained in the Dose Optimization Phase of the study, the Expansion Phase dose of Duvelisib will be determined.

In the Expansion Phase, approximately 90-100 patients may be enrolled and will receive Duvelisib dose in 28-day cycles as determined in Dose Optimization Phase.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Multi-Center, Phase 2, Open-label, Parallel Cohort Study of Efficacy and Safety of Duvelisib in Patients With Relapsed or Refractory Peripheral T Cell Lymphoma (PTCL)

Actual Study Start Date :

Feb 22, 2018

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

May 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Dose Optimization Phase: Cohort 1 Duvelisib PO BID at a starting dose of 25 mg, with potential escalation on a per-patient basis to 50 mg and then 75 mg, based on the patient's response to and tolerance of therapy, in 28-day cycles.	Drug: Duvelisib Duvelisib PO 25 mg BID or 50 mg BID or 75 mg BID in 28-day cycles.
Experimental: Dose Optimization Phase: Cohort 2 Duvelisib 75 mg PO BID, administered in 28-day cycles.	Drug: Duvelisib Duvelisib PO 75 mg BID in 28-day cycles.
Experimental: Expansion Phase Duvelisib administered in 28-day cycles (dose determined in Optimization Phase)	Drug: Duvelisib Duvelisib PO BID in 28-day cycles (dose determined in Optimization Phase)

Arm

Intervention/Treatment

Experimental: Dose Optimization Phase: Cohort 1

Duvelisib PO BID at a starting dose of 25 mg, with potential escalation on a per-patient basis to 50 mg and then 75 mg, based on the patient's response to and tolerance of therapy, in 28-day cycles.

Drug: Duvelisib

Duvelisib PO 25 mg BID or 50 mg BID or 75 mg BID in 28-day cycles.

Experimental: Dose Optimization Phase: Cohort 2

Duvelisib 75 mg PO BID, administered in 28-day cycles.

Drug: Duvelisib

Duvelisib PO 75 mg BID in 28-day cycles.

Experimental: Expansion Phase

Duvelisib administered in 28-day cycles (dose determined in Optimization Phase)

Drug: Duvelisib

Duvelisib PO BID in 28-day cycles (dose determined in Optimization Phase)

Outcome Measures

Primary Outcome Measures

Objective response rate (ORR) [From start of treatment to first documented response, assessed up to 2 cycles (58 days)]
Best response of CR or PR

Secondary Outcome Measures

Overall response rate (ORR) [From start of treatment until disease progression or unacceptable toxicity, assessed up to 2 cycles (58 days)]
Number of participants with Treatment-emergent adverse events (TEAEs) as assessed by CTCAE v4.0 [From start of treatment to end of treatment plus 30 days; 7 months]
Duration of Response (DOR) [Time from the first documentation of response to first documentation of progressive disease or death due to any cause, 6 months]
Progression-free survival (PFS) [Time from start of treatment to first documentation of progression or date of death from any cause, whichever came first, 4 months]
Disease control rate (DCR) [Greater than or equal to 8 weeks]
Overall survival (OS) [From start of treatment until death, 6 months]
Percentage of patients who receive the optimal dose of duvelisib [From start of treatment to end of cycle 1 (each cycle is 28 days)]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age ≥ 18 years of age
Diagnosis of one of the following histologic subtypes of PTCL, pathologically-confirmed, as defined by the World Health Organization:
Peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS);
Angioimmunoblastic T-cell lymphomas (AITL);
Anaplastic large cell lymphoma (ALCL); or
Natural-killer/T-cell lymphoma (NKTL)
Received at least 2 cycles of one prior regimen administered with curative intent and one of the following:
failed to achieve at least a partial response after 2 or more cycles;
failed to achieve a complete response after 6 or more cycles; and/or
progressed after an initial response
For patients with CD30+ ALCL, failed or are ineligible or intolerant to brentuximab vedotin
Measurable disease as defined by IWG for PTCL, i.e., at least 1 measurable disease lesion > 1.5 cm in at least one dimension by 18FDG-PET-CT, MRI, or diagnostic CT

Exclusion Criteria:

Clinical evidence of transformation to a more aggressive subtype of lymphoma
Received prior treatment with a phosphoinositide-3-kinase (PI3K) inhibitor
Known central nervous system involvement by PTCL
Ongoing treatment with chronic immunosuppressants (e.g., cyclosporine) or systemic steroids > 20 mg of prednisone (or equivalent) once daily (QD)
Ongoing treatment for systemic bacterial, fungal, or viral infection at Screening

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope National Medical Center	Duarte	California	United States	91010
2	University of California - Irvine	Irvine	California	United States	92691
3	University of California - Los Angeles	Los Angeles	California	United States	90404
4	Emory University Winship Cancer Institute	Atlanta	Georgia	United States	30322
5	Northwestern University - Feinberg School of Medicine	Chicago	Illinois	United States	60611
6	Norton Cancer Institute	Louisville	Kentucky	United States	40207
7	University of Maryland	Baltimore	Maryland	United States	20742
8	Dana Farber Cancer Institute	Boston	Massachusetts	United States	02215
9	Washington University	Saint Louis	Missouri	United States	63110
10	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10021
11	University of Rochester	Rochester	New York	United States	14627
12	Stony Brook Cancer Center	Stony Brook	New York	United States	11794
13	Levine Cancer Institute	Charlotte	North Carolina	United States	28204
14	Novant Health	Charlotte	North Carolina	United States	28204
15	Duke University	Durham	North Carolina	United States	27710
16	The Ohio State Univeristy	Columbia	Ohio	United States	43202
17	Toledo Cancer Center	Toledo	Ohio	United States	43623
18	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232
19	Baylor Research Institute - Charles Sammons Cancer Center	Dallas	Texas	United States	75246
20	Universitätsklinikum Halle (Saale) - Klinik und Poliklinik für Innere Medizin IV	Halle	Sachsen-Anhalt	Germany	06120
21	Universitätsklinikum Carl Gustav Carus	Dresden	Sachsen	Germany	01307
22	ASST Papa Giovanni XXIII - Medicina Trasfusionale ed Ematologia - Bergamo	Bergamo		Italy	24127
23	A.O.di Bologna Policl.S.Orsola	Bologna		Italy	40138
24	Ieo, Irccs	Milano		Italy	20141
25	Policlinico Universitario Agostino Gemelli, Università Cattolica del Sacro Cuore	Roma		Italy	00168
26	Azienda Ospedaliera Santa Maria di Terni	Terni		Italy	05100
27	Christie Hospital NHS Foundation Trust	Manchester		United Kingdom	M20 4BX
28	Nottingham University Hospitals NHS Trust	Nottingham		United Kingdom	NG5 1PB