Back to resultsStudy to Evaluate Safety and Preliminary Efficacy of Tafasitamab With Idelalisib or Venetoclax in R/R CLL/SLL Patients Pretreated With BTKi (COSMOS)
Primary Purpose
Leukemia, Lymphocytic, Chronic, B-Cell, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Tafasitamab
Idelalisib
Venetoclax
Sponsored by
About this trial
This is an interventional treatment trial for Leukemia, Lymphocytic, Chronic, B-Cell focused on measuring CD19, MOR208, MOR00208, CLL, SLL, COSMOS, tafasitamab
Eligibility Criteria
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
Sites / Locations
- Clinical Study Site
- Clinical Study Site
- Clinical Study Site
- Clinical Study Site
- Clinical Study Site
- Clinical Study Site
- Clinical Study Site
- Clinical Study Site
- Clinical Study Site
- Clinical Study Site
- Clinical Study Site
- Clinical Study Site
- Clinical Study Site
- Clinical Study Site
- Clinical Study Site
- Clinical Study Site
- Clinical Study Site
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Cohort A
Cohort B
Arm Description
tafasitamab (MOR208) in combination with idelalisib
tafasitamab (MOR208) in combination with venetoclax
Outcomes
Primary Outcome Measures
Incidence and Severity of Adverse Events (AEs)
For details please see Section of Adverse Events Overview
Secondary Outcome Measures
Best Objective Response Rate (ORR)
ORR = complete response [CR] + partial response [PR]; Local Evaluation
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
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)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02639910
Brief Title
Study to Evaluate Safety and Preliminary Efficacy of Tafasitamab With Idelalisib or Venetoclax in R/R CLL/SLL Patients Pretreated With BTKi
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
December 2021
Overall Recruitment Status
Completed
Study Start Date
November 2016 (Actual)
Primary Completion Date
November 2018 (Actual)
Study Completion Date
December 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
MorphoSys AG
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphocytic, Chronic, B-Cell, Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Keywords
CD19, MOR208, MOR00208, CLL, SLL, COSMOS, tafasitamab
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort A
Arm Type
Experimental
Arm Description
tafasitamab (MOR208) in combination with idelalisib
Arm Title
Cohort B
Arm Type
Experimental
Arm Description
tafasitamab (MOR208) in combination with venetoclax
Intervention Type
Biological
Intervention Name(s)
Tafasitamab
Other Intervention Name(s)
MOR208, MOR00208
Intervention Description
tafasitamab (MOR208) dose: 12 mg/kg intravenous infusion
Intervention Type
Drug
Intervention Name(s)
Idelalisib
Other Intervention Name(s)
Zydelig; GS-1101 or CAL-101
Intervention Description
idelalisib dose: 150 mg twice daily orally
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
Venclexta, Venclyxto; ABT-199
Intervention Description
venetoclax dose: 400 mg once daily orally
Primary Outcome Measure Information:
Title
Incidence and Severity of Adverse Events (AEs)
Description
For details please see Section of Adverse Events Overview
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Best Objective Response Rate (ORR)
Description
ORR = complete response [CR] + partial response [PR]; Local Evaluation
Time Frame
2 years
Title
Number of Participants With Treatment-emergent or Treatment-boosted Anti-MOR00208 Antibody Formation
Description
Number of participants with treatment-emergent or treatment-boosted anti-MOR00208 (anti-tafasitamab) antibody formation
Time Frame
2 years
Title
Maximum Plasma Concentration (Cmax) of MOR00208
Description
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)
Time Frame
At Cycle 3 Day 15
Other Pre-specified Outcome Measures:
Title
Proportion of Patients With MRD-negativity
Description
Proportion of patients who reached MRD-negativity in peripheral blood
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anke Muth
Organizational Affiliation
Clinical Development, MorphoSys AG
Official's Role
Study Director
Facility Information:
Facility Name
Clinical Study Site
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32204
Country
United States
Facility Name
Clinical Study Site
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Clinical Study Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Clinical Study Site
City
Graz
ZIP/Postal Code
8036
Country
Austria
Facility Name
Clinical Study Site
City
Salzburg
ZIP/Postal Code
5020
Country
Austria
Facility Name
Clinical Study Site
City
Wien
ZIP/Postal Code
1090
Country
Austria
Facility Name
Clinical Study Site
City
Dresden
ZIP/Postal Code
1307
Country
Germany
Facility Name
Clinical Study Site
City
Leipzig
ZIP/Postal Code
4103
Country
Germany
Facility Name
Clinical Study Site
City
Muenchen
ZIP/Postal Code
80804
Country
Germany
Facility Name
Clinical Study Site
City
Brescia
ZIP/Postal Code
25123
Country
Italy
Facility Name
Clinical Study Site
City
Milano
ZIP/Postal Code
20162
Country
Italy
Facility Name
Clinical Study Site
City
Gdansk
ZIP/Postal Code
80952
Country
Poland
Facility Name
Clinical Study Site
City
Krakow
ZIP/Postal Code
30510
Country
Poland
Facility Name
Clinical Study Site
City
Lublin
ZIP/Postal Code
85094
Country
Poland
Facility Name
Clinical Study Site
City
Opole
ZIP/Postal Code
45372
Country
Poland
Facility Name
Clinical Study Site
City
Bournemouth
ZIP/Postal Code
BH7 7DW
Country
United Kingdom
Facility Name
Clinical Study Site
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
34414843
Citation
Staber PB, Jurczak W, Greil R, Vucinic V, Middeke JM, Montillo M, Munir T, Neumeister P, Schetelig J, Stilgenbauer S, Striebel F, Dirnberger-Hertweck M, Weirather J, Brugger W, Kelemen P, Wendtner CM, Woyach JA. Tafasitamab combined with idelalisib or venetoclax in patients with CLL previously treated with a BTK inhibitor. Leuk Lymphoma. 2021 Dec;62(14):3440-3451. doi: 10.1080/10428194.2021.1964020. Epub 2021 Aug 20.
Results Reference
derived
Learn more about this trial
Study to Evaluate Safety and Preliminary Efficacy of Tafasitamab With Idelalisib or Venetoclax in R/R CLL/SLL Patients Pretreated With BTKi
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