A Study Evaluating Safety, PK, and Efficacy of Tafasitamab and Parsaclisib in Participants With Relapsed/Refractory Non Hodgkin Lymphoma (R/R NHL) or Chronic Lymphocytic Leukemia (CLL)

Chronic Lymphocytic Leukemia Clinical Trial

— topMIND  

Official title:

A Phase 1b/2a Basket Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Combination Therapy With the Anti CD19 Monoclonal Antibody Tafasitamab and the PI3Kδ Inhibitor Parsaclisib in Adult Participants With Relapsed/Refractory Non Hodgkin Lymphoma or Chronic Lymphocytic Leukemia

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04809467
• Other study ID #: INCMOR 0208-101
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: September 16, 2021
• Est. completion date: December 15, 2024

Study information

• Verified date: June 2024
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this single-arm, open-label, Phase 1b/2a, multicenter basket study is to evaluate whether tafasitamab and parsaclisib can be safely combined at the recommended Phase 2 dose (RP2D) and dosing regimen that was established for each of the 2 compounds as a treatment option for adult participants with R/R B-cell malignancies.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 54
• Est. completion date: December 15, 2024
• Est. primary completion date: December 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed R/R B-cell malignancy: DLBCL (THRLBCL, EBV-positive DLBCL of the elderly, Grade 3b FL, HGBL with MYC and BCL2 and/or BCL6 rearrangements, transformed lymphoma); MCL ((with cyclin D1 overexpression or t(11;14); FL (Grade 1, 2, 3a); MZL (extranodal, nodal, splenic) ; CLL, or SLL

• Willingness to undergo biopsy

• At least 2 prior systemic treatment regimens, including prior treatment with an anti-CD20 antibody (all cohorts) or prior treatment with a BTK inhibitor (CLL/SLL)

• Relapsed, progressive, or refractory NHL or CLL

• For NHL/SLL: Radiographically measurable nodal or extranodal disease (all cohorts except CLL)

• ECOG-PS 0 - 2

• LVEF = 50%

• Adequate renal, hepatic, bone marrow function

Exclusion Criteria:

• Any other histological type of lymphoma

• Primary or secondary CNS lymphoma

• Anticancer and/or investigational therapy within the past 30 days or 5 half-lives

• Allogeneic stem cell transplantation within the past 6 months, or ASCT within 3 months before C1D1

• Previous treatment with CD19-targeted therapy or PI3K inhibitors

• Clinically significant cardiac disease

• Other malignancy within the past 3 years

• Active graft-versus-host disease

• Stroke or intracranial hemorrhage within the past 6 months

• Chronic or current active infectious disease

• Positive virus serology for HCV, HBV, HIV

• Currently pregnant or breastfeeding

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, Non-Hodgkin
• Non Hodgkin Lymphoma

Intervention

Drug:
• tafasitamab
tafasitamab will be administered at a protocol defined dose once a week for cycles 1-3 and every other week from cycle 4 until progression.
• parsaclisib
parsaclisib will be administered at protocol defined dose for cycles 1 through disease progression.

Locations

Country	Name	City	State
Austria	Ordensklinikum Linz Gmbh Elisabethinen	Linz
Austria	Landeskrankenhaus Salzburg	Salzburg
Austria	Hanusch-Krankenhaus Der Wiener Gebietskrankenkasse	Vienna
Belgium	Institut Jules Bordet	Brussels
Belgium	Grand Hospital de Charleroi	Charleroi
Belgium	Universitair Ziekenhuis Antwerpen (Uza)	Edegem
Belgium	Az Groeninge Campus Kennedylaan	Kortrijk
Belgium	Universitair Ziekenhuis (Uz) Leuven	Leuven
Belgium	AZ DELTA	Roeselare
France	University Hospital Brest	Brest
France	Centre Hospitalier Universitaire de Nantes (Chu de Nantes) - Hotel-Dieu	Nantes
France	Centre Henri Becquerel	Rouen
France	Institut Gustave Roussy	Villejuif
Germany	University Medical Center Freiburg	Freiburg
Germany	Justus-Liebig University	Giessen
Germany	Universitatsmedizin Der Johannes Gutenberg-Universitat Mainz Iii	Mainz
Germany	University Hospital Wurzburg	Wurzburg
Italy	S Orsolas University Hospital Seragnoli Institute of Hematology	Bologna
Italy	Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori	Meldola
Italy	Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda	Milan
Italy	Fondazione Irccs Istituto Nazionale Dei Tumori	Milan
Italy	Istituto Nazionale Tumori Irccs Fondazione Pascale	Naples
Italy	Azienda Ospedaliera Ospedali Riuniti Villa Sofia - Cervello	Palermo
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa
Italy	Ospedale Santa Maria Delle Croci	Ravenna
Italy	Irccs Istituto Clinico Humanitas	Rozzano
Spain	Hospital General Unviersitario de Alicante	Alicante
Spain	Hopital Sant Pau	Barcelona
Spain	Hospital General Universitario Vall D Hebron	Barcelona
Spain	Ico Institut Catala D Oncologia	Barcelona
Spain	Hospital Universitario San Cecilio	Granada
Spain	Centro Integral Oncologico Clara Campal (Ciocc)	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Quironsalud Madrid	Madrid
Spain	Hospital Puerta de Hierro	Majadahonda
Spain	Hospital Universitario Central de Asturias	Oviedo
Spain	Hospital Clinico Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Marques de Valdecilla	Santander
Spain	Hospital Universitario Virgen Del Rocio	Sevilla
Spain	Hospital General Universitario de Valencia	Valencia
United States	University of Michigan	Ann Arbor	Michigan
United States	Cancer Center For Blood Disorders	Bethesda	Maryland
United States	University of Alabama At Birmingham Comprehensive Cancer Center	Birmingham	Alabama
United States	Ohio State University	Columbus	Ohio
United States	Community Health Network, Inc.	Indianapolis	Indiana
United States	Indiana Blood and Marrow Transplantation	Indianapolis	Indiana
United States	University of Southern California	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	Clinical Research Alliance	New Hyde Park	New York
United States	Jefferson University Hospitals	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  France,  Germany,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase 1b : Number of Treatment Emergent Adverse Events	Any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug.	Up to 25 months
Primary	Phase 1b : Incidence of Dose Limiting Toxicities	Dose-limiting toxicity will be defined as the occurrence of any of the toxicities as per protocol. All DLTs will be assessed for severity by the investigator using CTCAE v5.0 criteria.	28 Days
Secondary	Phase 2a : Overall Response Rate	Defined as the percentage of participants experiencing a best response of Complete Response/Complete Metabolic Response (CR/CMR) or Partial Response/Partial Metabolic Response (PR/PMR) according to the Lugano criteria (Cheson et al 2014) for NHL and the iwCLL criteria (Hallek et al 2018) for CLL.	Up to 25 months
Secondary	Pharmacokinetics Parameter : Cmax of tafasitamab	Maximum Observed Plasma Concentration of tafasitamab	Up to 24 months
Secondary	Pharmacokinetics Parameter : Cmin of tafasitamab	Minimum Observed Plasma Concentration of tafasitamab	Up to 24 months
Secondary	Pharmacokinetics Parameter : Tmax of tafasitamab	Time to reach maximum plasma concentration of tafasitamab	Up to 24 months
Secondary	Pharmacokinetics Parameter : AUC(t) of tafasitamab	Area under the concentration-time curve from time zero to time of tafasitamab	Up to 24 months
Secondary	Pharmacokinetics Parameter : Ctrough of tafasitamab	C trough concentration of tafasitamab	Up to 24 months