Study to Evaluate Safety and Preliminary Efficacy of Tafasitamab With Idelalisib or Venetoclax in R/R CLL/SLL Patients Pretreated With BTKi

Chronic Lymphocytic Leukemia Clinical Trial

— COSMOS  

Official title:

A Phase II, Two-Cohort, Open-Label, Multicenter Study to Evaluate the Safety and Preliminary Efficacy of MOR00208 Combined With Idelalisib or Venetoclax in Patients With Relapsed or Refractory CLL/SLL Previously Treated With Bruton's Tyrosine Kinase (BTK) Inhibitor

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02639910
• Other study ID #: MOR208C205
• Status: Completed
• Phase: Phase 2
• Start date: November 2016
• Est. completion date: December 2021

Study information

• Verified date: December 2021
• Source: MorphoSys AG
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a two-cohort, multicenter, open-label study of tafasitamab (MOR208) combined with idelalisib or venetoclax in adult patients with R/R CLL or R/R SLL pretreated with a BTK inhibitor (e.g., ibrutinib) as single agent or as part of combination therapy. Patients completing the study treatment are invited to participate in an optional biomarker sub-study.

Description:

The purpose of this study is to evaluate the clinical safety and preliminary efficacy of tafasitamab (MOR208) combined with idelalisib or venetoclax. The study will include safety run-in phase for each cohort with an evaluation of the safety data by an Independent Data Monitoring Committee.

An optional sub-study has been introduced to collect biological samples for investigations on biomarkers (e.g., CD19 expression) after tafasitamab treatment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: December 2021
• Est. primary completion date: November 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Major inclusion criteria

Diagnosis/Trial Population

• Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL):

• history of diagnosis of CLL or SLL that meets IWCLL diagnostic criteria

• histologically confirmed diagnosis of SLL by lymph node biopsy

• indication for treatment as defined by the IWCLL guidelines

• Patients must have both of the following:

• relapsed or refractory disease while receiving a BTKi therapy or intolerance of such therapy

• single-agent or combination therapy with a BTKi for at least one month must be the patient's most recent prior anticancer therapy

• ECOG performance status of 0 to 2

• Patients with a past medical history of autologous or allogeneic stem cell transplantation must exhibit full hematological recovery

Laboratory Values

• Patients must meet adequate bone marrow function and adequate hepatic and renal function

Other Inclusion Criteria

• Females of childbearing potential must use a highly effective method of contraception

Major exclusion criteria

Diagnosis

• Patients who have:

• non-Hodgkin's lymphomas other than CLL/SLL

• transformed CLL/SLL or Richter's syndrome

• active and uncontrolled autoimmune cytopenia

Previous and Current Treatment

• Patients who have received treatment with a BTK inhibitor within 5 days prior to Day 1 dosing

• Patients who have, within 14 days prior to D1 dosing:

• not discontinued CD20-targeted therapy, chemotherapy, radiotherapy, investigational anticancer therapy or other lymphoma specific therapy

• systemic corticosteroids in doses greater than prednisone equivalent to 20 mg/day with the exception of patients with signs of rapidly progressing disease

• received live vaccines with the exception of vaccination against influenza with inactivated virus or for pneumococcal diseases

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Small Lymphocytic Lymphoma

Intervention

Biological:
• Tafasitamab
tafasitamab (MOR208) dose: 12 mg/kg intravenous infusion

Drug:
• Idelalisib
idelalisib dose: 150 mg twice daily orally
• Venetoclax
venetoclax dose: 400 mg once daily orally

Locations

Country	Name	City	State
Austria	Clinical Study Site	Graz
Austria	Clinical Study Site	Salzburg
Austria	Clinical Study Site	Wien
Germany	Clinical Study Site	Dresden
Germany	Clinical Study Site	Leipzig
Germany	Clinical Study Site	Muenchen
Italy	Clinical Study Site	Brescia
Italy	Clinical Study Site	Milano
Poland	Clinical Study Site	Gdansk
Poland	Clinical Study Site	Krakow
Poland	Clinical Study Site	Lublin
Poland	Clinical Study Site	Opole
United Kingdom	Clinical Study Site	Bournemouth
United Kingdom	Clinical Study Site	Leeds
United States	Clinical Study Site	Columbus	Ohio
United States	Clinical Study Site	Jacksonville	Florida
United States	Clinical Study Site	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
MorphoSys AG

Countries where clinical trial is conducted

United States,  Austria,  Germany,  Italy,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Proportion of Patients With MRD-negativity	Proportion of patients who reached MRD-negativity in peripheral blood	2 years
Primary	Incidence and Severity of Adverse Events (AEs)	For details please see Section of Adverse Events Overview	2 years
Secondary	Best Objective Response Rate (ORR)	ORR = complete response [CR] + partial response [PR]; Local Evaluation	2 years
Secondary	Number of Participants With Treatment-emergent or Treatment-boosted Anti-MOR00208 Antibody Formation	Number of participants with treatment-emergent or treatment-boosted anti-MOR00208 (anti-tafasitamab) antibody formation	2 years
Secondary	Maximum Plasma Concentration (Cmax) of MOR00208	Mean Cmax of tafasitamab (MOR00208) at Cycle 3 Day 15 (after the weekly dosing of tafasitamab in Cycles 1 to 3 including a loading dose at C1D4)	At Cycle 3 Day 15