Clinical trial NCT02639910: Study to Evaluate Safety and Preliminary Efficacy of Tafasitamab With Idelalisib or Venetoclax in R/R CLL/SLL Patients Pretreated With BTKi
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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia, Lymphocytic, Chronic, B-Cell
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Keywords: CD19
MOR208
MOR00208
CLL
SLL
COSMOS
tafasitamab
Lead sponsor: MorphoSys AG
Sponsor class: INDUSTRY
First posted: 2015-12-28
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Incidence and Severity of Adverse Events (AEs)
timeFrame: 2 years
Secondary outcomes:
measure: Best Objective Response Rate (ORR)
timeFrame: 2 years
measure: Number of Participants With Treatment-emergent or Treatment-boosted Anti-MOR00208 Antibody Formation
timeFrame: 2 years
measure: Maximum Plasma Concentration (Cmax) of MOR00208
timeFrame: At Cycle 3 Day 15
Other outcomes:
measure: Proportion of Patients With MRD-negativity
timeFrame: 2 years
Locations:
city: Jacksonville
country: United States
facility: Clinical Study Site
state: Florida
city: Rochester
country: United States
facility: Clinical Study Site
state: Minnesota
city: Columbus
country: United States
facility: Clinical Study Site
state: Ohio
city: Graz
country: Austria
facility: Clinical Study Site
city: Salzburg
country: Austria
facility: Clinical Study Site
city: Wien
country: Austria
facility: Clinical Study Site
city: Dresden
country: Germany
facility: Clinical Study Site
city: Leipzig
country: Germany
facility: Clinical Study Site
city: Muenchen
country: Germany
facility: Clinical Study Site
city: Brescia
country: Italy
facility: Clinical Study Site
city: Milano
country: Italy
facility: Clinical Study Site
city: Gdansk
country: Poland
facility: Clinical Study Site
city: Krakow
country: Poland
facility: Clinical Study Site
city: Lublin
country: Poland
facility: Clinical Study Site
city: Opole
country: Poland
facility: Clinical Study Site
city: Bournemouth
country: United Kingdom
facility: Clinical Study Site
city: Leeds
country: United Kingdom
facility: Clinical Study Site
Study officials:
affiliation: Clinical Development, MorphoSys AG
name: Anke Muth
role: STUDY_DIRECTOR
References:
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.