INCB050465 in Combination With Rituximab, Bendamustine and Rituximab, or Ibrutinib in Participants With Previously Treated B-Cell Lymphoma (CITADEL-112)

Sponsor

Incyte Corporation (Industry)

Overall Status

Completed

CT.gov ID

NCT03424122

Collaborator

(none)

Enrollment

Locations

Arms

47.8

Actual Duration (Months)

2.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of parsaclisib when combined with rituximab, bendamustine and rituximab, or ibrutinib in participants with relapsed or refractory B-cell lymphoma.

Condition or Disease	Intervention/Treatment	Phase
B-cell Lymphoma	Drug: Parsaclisib Drug: Rituximab Drug: Bendamustine Drug: Ibrutinib	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

50 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1, Open-Label, Dose-Finding Study of INCB050465 in Combination With Investigator Choice of Rituximab, Bendamustine and Rituximab, or Ibrutinib in Participants With Previously Treated B-Cell Lymphoma (CITADEL-112)

Actual Study Start Date :

Jul 2, 2018

Actual Primary Completion Date :

Jun 27, 2022

Actual Study Completion Date :

Jun 27, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment A Parsaclisib + Rituximab	Drug: Parsaclisib Parsaclisib administered orally once daily for 8 weeks followed by once weekly. Other Names: INCB050465 Drug: Rituximab Rituximab administered intravenously at the protocol-defined dose regimen according to treatment group. Other Names: Rituxan
Experimental: Treatment B Parsaclisib + Bendamustine + Rituximab	Drug: Parsaclisib Parsaclisib administered orally once daily for 8 weeks followed by once weekly. Other Names: INCB050465 Drug: Rituximab Rituximab administered intravenously at the protocol-defined dose regimen according to treatment group. Other Names: Rituxan Drug: Bendamustine Bendamustine administered intravenously on Days 1 and 2 of each cycle for up to 6 cycles. Other Names: Treanda, Bendeka
Experimental: Treatment C Parsaclisib + Ibrutinib	Drug: Parsaclisib Parsaclisib administered orally once daily for 8 weeks followed by once weekly. Other Names: INCB050465 Drug: Ibrutinib Ibrutinib administered orally once daily. Other Names: Imbruvica

Arm

Intervention/Treatment

Experimental: Treatment A

Parsaclisib + Rituximab

Drug: Parsaclisib

Parsaclisib administered orally once daily for 8 weeks followed by once weekly.

Other Names:

INCB050465

Drug: Rituximab

Rituximab administered intravenously at the protocol-defined dose regimen according to treatment group.

Other Names:

Rituxan

Experimental: Treatment B

Parsaclisib + Bendamustine + Rituximab

Drug: Parsaclisib

Parsaclisib administered orally once daily for 8 weeks followed by once weekly.

Other Names:

INCB050465

Drug: Rituximab

Rituximab administered intravenously at the protocol-defined dose regimen according to treatment group.

Other Names:

Rituxan

Drug: Bendamustine

Bendamustine administered intravenously on Days 1 and 2 of each cycle for up to 6 cycles.

Other Names:

Treanda, Bendeka

Experimental: Treatment C

Parsaclisib + Ibrutinib

Drug: Parsaclisib

Parsaclisib administered orally once daily for 8 weeks followed by once weekly.

Other Names:

INCB050465

Drug: Ibrutinib

Ibrutinib administered orally once daily.

Other Names:

Imbruvica

Outcome Measures

Primary Outcome Measures

Number of treatment-emergent adverse events (TEAEs) [Up to approximately 12 months.]
A TEAE is any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study treatment.

Secondary Outcome Measures

Apparent clearance of parsaclisibin combination with rituximab, bendamustine and rituximab, or ibrutinib [Up to approximately 1 month.]
Measured to assess the plasma pharmacokinetic profile of parsaclisib in combination with rituximab, bendamustine and rituximab, and ibrutinib.
Apparent volume of distribution of parsaclisib in combination with rituximab, bendamustine and rituximab, or ibrutinib [Up to approximately 1 month.]
Measured to assess the plasma pharmacokinetic profile of parsaclisib in combination with rituximab, bendamustine and rituximab, and ibrutinib.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Men and women, aged 18 years or older on the day of signing the Informed Consent Form (ICF).
Histologically confirmed indolent/aggressive DLBCL, FL, MZL, or MCL.
Participants with DLBCL, MZL or MCL must have received at least 1 prior line of systemic therapy with documented progression or documented failure to achieve CR or PR after the most recent systemic treatment regimen.
Participants with FL must have received at least 2 prior lines of systemic therapy with documented progression or documented failure to achieve CR or PR after the most recent systemic treatment regimen.
Ineligible for stem cell transplant.
Participants with DLBCL must have failed or refused stem cell transplantation or failed first-line salvage therapy if ineligible for transplantation.
Must be willing to undergo an incisional or excisional lymph node or tissue biopsy or to provide a lymph node or tissue biopsy from the most recent available archival tissue.
Life expectancy of > 3 months.
Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2 (see Appendix D).
Willingness to avoid pregnancy or fathering a child.
Ability to comprehend and willingness to sign an ICF

Exclusion Criteria:

Evidence of transformed non-Hodgkin lymphoma histologies (with the exception of FL).
Histologically confirmed rare non-Hodgkin B-cell subtypes.
History of or central nervous system lymphoma (either primary or metastatic) or leptomeningeal disease.
Prior treatment with idelalisib, other selective PI3Kδ inhibitors, or a pan-PI3K inhibitor.
For participants to be treated with bendamustine (Treatment B), prior treatment with bendamustine (within 12 months of the start of study treatment). Participants with prior bendamustine treatment (> 12 months before the start of study treatment) are eligible if they meet the following criteria:
Did not discontinue because of tolerability concerns.
Achieved either partial response (PR) or complete response (CR) to the bendamustine regimen of at least 12 months in duration before relapse/progression.
Experienced progression following a regimen containing an alkylating agent.
For participants to be treated with ibrutinib (Treatment C), prior treatment with a Bruton's tyrosine kinase (BTK) inhibitor.
Allogeneic stem cell transplant within the last 6 months or autologous stem cell transplant within the last 3 months before the date of the first dose of study treatment.
Active graft-versus-host disease following allogeneic transplant.
Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arizona Cancer Center - Out Pt.	Tucson	Arizona	United States	85719
2	Indiana Blood and Marrow Transplantation	Indianapolis	Indiana	United States	46237
3	Comprehensive Cancer Center of Nevada	Las Vegas	Nevada	United States	89169
4	Texas Oncology	Austin	Texas	United States	78705
5	Baylor Charles A. Sammons Cancer Center	Dallas	Texas	United States	75246
6	Baylor College of Medicine	Houston	Texas	United States	77030
7	Smith Clinic	Houston	Texas	United States	77054
8	Cancer Care Centers of South Texas	San Antonio	Texas	United States	78217
9	Texas Oncology San Antonio	San Antonio	Texas	United States	78240
10	Asst Spedali Civili Di Brescia	Brescia		Italy	25123
11	Azienda Ospedaliera San Gerardo Di Monza	Monza		Italy	20835
12	Azienda Ospedaliera Universitaria Pisana	Pisa		Italy	56126
13	Ospedale Delle Croci - Ematologia Ravenna	Ravenna		Italy	48121
14	Hospital Germans Trias I Pujol	Badalona		Spain	08916
15	Hospital General Universitari Vall D Hebron	Barcelona		Spain	08035
16	Hospital Clinic I Provincial	Barcelona		Spain	08036
17	Fundacion Jimenez Diaz University Hospital	Madrid		Spain	28040
18	Hospital Universitario Hm Sanchinarro	Madrid		Spain	28050
19	Hospital Clinico Universitario de Salamanca	Salamanca		Spain	37007
20	Hospital Universitario Virgen Del Rocio	Sevilla		Spain	41013
21	Hospital Universitario Y Politecnic La Fe	Valencia		Spain	46026