Selinexor (KPT-330) in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Diffuse Large B-cell Lymphoma Clinical Trial

Official title:

A Phase 2b Open-label Study of Selinexor (KPT-330) in Patients With Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02227251
• Other study ID #: KCP-330-009
• Secondary ID: 2014-001977-15
• Status: Recruiting
• Phase: Phase 2
• Start date: November 2014
• Est. completion date: November 2027

Study information

• Verified date: June 2024
• Source: Karyopharm Therapeutics Inc
• Contact: Karyopharm Medical Information
• Phone: (888) 209-9326
• Email: clinicaltrials[@]karyopharm.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

A multicenter, open-label Phase 2b study of selinexor (KPT-330) in participants with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who have no therapeutic options of demonstrated clinical benefit.

Description:

This is a multicenter, open label, Phase 2b study of the selective inhibitor of nuclear export (SINE) selinexor (40 or 60 milligrams [mg]) given orally (PO) to participants with R/R DLBCL). The study is being conducted in 2 parts (Part 1 and Part 2). For Part 1, a fixed 60 mg dose of selinexor is given orally to 130 participants with R/R DLBCL who have no therapeutic options of demonstrated clinical benefit and who meet eligibility criteria and have none of the exclusion criteria will be enrolled to receive selinexor until either disease progression or intolerance has occurred. For Part 2, approximately 110 participants (55 in each arm) are planned to be enrolled. Participants will be randomized (open label) in a 1:1 ratio to either Arm A (40 mg) or Arm B (60 mg) and will be stratified based on history of prior autologous stem cell transplantation (ASCT) versus no prior ASCT. All the participants will be followed until disease progression and/or death.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 244
• Est. completion date: November 2027
• Est. primary completion date: April 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria (Parts 1 and 2):

• Written informed consent in accordance with federal, local, and institutional guidelines. The participant must provide informed consent prior to the first screening procedure.
• Age greater than or equal to (=) 18 years.
• ECOG performance status of less than or equal to (=) 2.
• Participants should have estimated life expectancy of greater than (>) 3 months at study entry.
• Previously treated, pathologically confirmed de novo DLBCL, or DLBCL transformed from previously diagnosed indolent lymphoma (e.g., follicular lymphoma).
• Participants must have received at least 2 but no more than 5 previous systemic regimens for the treatment of their de novo or transformed DLBCL including (i) at least 1 course of anthracycline-based chemotherapy (unless absolutely contraindicated due to cardiac dysfunction, in which case other active agents such as etoposide, bendamustine, or gemcitabine must have been given) and (ii) at least 1 course of anti-CD20 immunotherapy (e.g., rituximab), unless contraindicated due to severe toxicity. Participants who were considered ineligible for standard multi-agent immunochemotherapy must have received at least 2 and no more than 5 prior treatment regimens including at least 1 course of anti-CD20 antibodies and must be approved by the Medical Monitor. Prior stem cell transplantation is allowed; induction, consolidation, stem cell collection, preparative regimen and transplantation ± maintenance are considered a single line of therapy.
• Female participants of child-bearing potential must have a negative serum pregnancy test at screening and agree to use reliable methods of contraception for 3 months after their last dose of medication. Male participants must use a reliable method of contraception if sexually active with a female of child-bearing potential. For both male and female participants, effective methods of contraception must be used throughout the study and for 3 months following the last dose.

Part 1 additional inclusion criteria:

• For participants whose most recent systemic anti-DLBCL therapy induced a PR or CR, at least 60 days must have elapsed since the end of that therapy. For all other participants, at least 14 weeks (98 days) must have elapsed since the end of their most recent systemic anti-DLBCL therapy. . Palliative localized radiation within the therapy-free interval is allowed. Non-chemotherapy maintenance will not be considered anti DLBCL therapy, and therefore is allowed during the therapy-free interval.
• Documented clinical or radiographic evidence of progressive DLBCL prior to dosing.
• Participants must have measurable disease per the revised criteria for response assessment of lymphoma. Lymph nodes should be considered abnormal if the long axis is >1.5 centimeter (cm), regardless of the short axis. If a lymph node has a long axis of 1.1 to 1.5 cm, it should only be considered abnormal if its short axis is >1.0. Lymph nodes =1.0 by =1.0 will not be considered abnormal for relapse or PD.

Part 2 additional inclusion criteria:

• At least 3 weeks (21 days) must have elapsed since the end of participant's most recent systemic anti-DLBCL therapy (prior to Cycle 1 Day 1). Palliative localized radiation within the therapy-free interval is allowed.Non-chemotherapy maintenance will not be considered anti-DLBCL therapy, and therefore is allowed during the therapy-free interval.
• Adequate hematopoietic function: (i) Hemoglobin =10.0 grams per deciliters (g/dL) within 14 days of starting therapy (participant may receive red blood cell [RBC] transfusion within 14 days). (ii) Absolute neutrophil count =1000 cells/millimeter (mm^3) (use of granulocyte growth factors prior to and during the study is acceptable). (iii) Platelet count =100,000/mm^3 within 14 days of starting therapy (use of platelet growth factors prior to and during the study is acceptable).
• Participants must have measurable disease per the revised criteria for response assessment of lymphoma. Lymph nodes should be considered abnormal if the long axis is >1.5 cm, regardless of the short axis. Extranodal lesion should be considered abnormal if the long axis is >1.0 cm.

Exclusion Criteria (Parts 1 and 2):

• Participants who are pregnant or lactating.
• Primary mediastinal (thymic) large B-cell lymphoma (PMBL)
• Participants must not be eligible for high-dose chemotherapy with autologous stem cell transplantation rescue (Investigator must provide detailed documentation for ineligibility).
• Participants who have not recovered to Grade =1 clinically significant adverse events, or to their baseline, from their most recent systemic anti-DLBCL therapy.
• Major surgery within 2 weeks of first dose of study treatment.
• Participants with active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infections.
• Psychiatric illness or substance use that would prevent the participant from giving informed consent or being compliant with the study procedures.
• Any of the following laboratory abnormalities:

(i) A circulating lymphocyte count of >50,000/L. (ii) Hepatic dysfunction: bilirubin >2.0 times the upper limit of normal (ULN) (except participants with Gilbert's syndrome: total bilirubin of >3*ULN) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >2.5 times ULN. In participants with known liver involvement of their DLBCL, AST and ALT >5*ULN. (iii) Severe renal dysfunction: estimated creatinine clearance of <30 mL/min, measured in 24-hour urine or calculated using the formula of Cockroft and Gault [(140-Age)*Mass (kg)/(72*creatinine mg/dL); multiply by 0.85 if female].

• Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the participant's safety.
• Participants with active graft-versus-host disease after allogeneic stem cell transplantation. At least 4 months must have elapsed since completion of allogeneic stem cell transplantation.
• Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals on Cycle 1 Day 1; however, prophylactic use of these agents is acceptable even if parenteral.
• Participants unable to swallow tablets, participants with malabsorption syndrome, or any other gastrointestinal disease or gastrointestinal dysfunction that could interfere with absorption of study treatment.

Part 1 additional exclusion criteria:

• For participants whose most recent systemic anti-DLBCL therapy induced a PR or CR:

Radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer therapy other than glucocorticoids <60 days or <14 weeks prior to Cycle 1 Day 1.

• Known central nervous system lymphoma or meningeal involvement.
• DLBCL with mucosa-associated lymphoid tissue [MALT] lymphoma, composite lymphoma (Hodgkin's lymphoma+NHL), or DLBCL transformed from diseases other than indolent NHL.
• Unstable cardiovascular function:

(i) Symptomatic ischemia, or (ii) Uncontrolled clinically significant conduction abnormalities (i.e., ventricular tachycardia on anti-arrhythmia are excluded; 1st degree atrioventricular block or asymptomatic left anterior fascicular block /right bundle branch block will not be excluded), or (iii) Congestive heart failure of New York Heart Association Class =3, or (iv) Myocardial infarction within 3 months.

• Participants with a BSA <1.4 m^2 as calculated per Dubois 1916 or Mosteller 1987.
• Any of the following laboratory abnormalities:

(i) Absolute neutrophil count (ANC) <1000 cells/mm^3 or platelet count <75,000/mm^3 during screening and on Cycle 1 Day 1. Use of granulocyte-stimulating factors and platelet growth factors prior to and during the study is acceptable. (ii) Hematopoietic dysfunction: hemoglobin < 10.0 g/dL within 14 days of and including Cycle 1 Day 1 and/or patients receiving red blood cell (RBC) transfusion within 14 days of and including Cycle 1 Day 1.

• Participants who have been committed to an institution by official or judicial order.
• Participants with dependency on the Sponsor, Investigator or study site.

Part 2 additional exclusion criteria:

• Participants with active HBV, HVC, or HIV infections. Participants with active HBV are allowed if antiviral therapy for hepatitis B has been given for >8 weeks and viral load is <100 International units per milliliters (IU/mL) prior to first dose of study treatment. Participants with known history of HCV or found to be HCV antibody positive on screening, are allowed if there is documentation of negative viral load per institutional standard. Participants with HIV who have CD4+T-cell counts =350 cells/microliter (mcL), negative viral load per institutional standard, and no history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections in the last year are allowed.
• Known active central nervous system lymphoma or meningeal involvement. Participants with a history of CNS disease treated into remission may be enrolled.
• DLBCL with MALT lymphoma, composite lymphoma (Hodgkin's lymphoma + NHL), DLBCL arising from CLL (Richter's transformation), or high-grade B-cell lymphoma.
• Received strong cytochrome P450 3A (CYP3A) inhibitors =7 days prior to Day 1 dosing or strong CYP3A inducers =14 days prior to Day 1 dosing.

Related Conditions & MeSH terms

• Diffuse Large B-cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• Selinexor
Dose: 60 mg (BIW); Dosage form: film-coated (20 mg each) immediate release tablets; Route of administration: Oral
• Selinexor
Dose: 40 mg (BIW); Dosage form: film-coated (20 mg each) immediate release tablets; Route of administration: Oral
• Selinexor
Dose: 60 mg (BIW) and 60 mg (QW); Dosage form: film-coated (20 mg each) immediate release tablets; Route of administration: Oral

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Monash Medical Centre	Clayton	Victoria
Australia	St. Vincent's Hospital Sydney	Darlinghurst	New South Wales
Australia	Epworth Hospital	East Melbourne	Victoria
Australia	St. Vincent's Melbourne	Fitzroy	Victoria
Australia	Ashford Cancer Centre	Kurralta Park	South Australia
Australia	Liverpool Hospital, Ingham Institute of Medical Research	Liverpool	New South Wales
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Fiona Stanley Hospital	Murdoch	Western Australia
Australia	Icon Cancer Care	South Brisbane	Queensland
Australia	Calvary Mater Newcastle Hospital	Waratah	New South Wales
Austria	Medical University of Graz	Graz
Austria	Medizinische Universität Innsbruck für Innere Medizin	Innsbruck
Austria	LKH Leoben Department for Haemato-Oncology	Leoben
Austria	Akh Linz Innere Med III - Zentrum für Hämatologie und med. Onkologie	Linz
Austria	Krankenhaus Barmherzigen Schwestern Linz	Linz
Austria	Krankenhaus der Elisabethinen Linz GmbH	Linz
Austria	Uni. Klinik für Innere Medizin III Universitätsklinikum der PMU LKH Salzburg	Salzburg
Austria	Medical University of Vienna (MUW) Department of Medicine I	Vienna
Austria	Univ. General Hospital Hietzing	Vienna
Belgium	Ziekenhuis Netwerk Antwerpen	Antwerpen
Belgium	AZ Sint-Jan	Bruges
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Institut Jules Bordet	Brussels
Belgium	UZ Gent	Gent
Belgium	CH Jolimont	La Louviere
Belgium	AZ Delta	Roeselare
Belgium	H-Hartziekenhuis Roeselare-Menen	Roeselare
Bulgaria	University Hospital for Active Treatment Dr. Georgi Stranski	Pleven
Bulgaria	Specialized Hospital for Active Treatment of Haematological Diseases EAD	Sofia
Bulgaria	University Multiprofile Hospital for Active Treatment Sveti Ivan Rilski EAD	Sofia
Canada	Sir Mortimer B Davis Jewish General Hospital/McGill University	Montreal	Quebec
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
France	Centre Hospitalier Universitaire Henri Mondor	Créteil
France	Unite Hemopathies Lymphoides Chu Henri Mondor	Créteil
France	Chu Dijon-Bourgogne - Hematologie Clinique	Dijon
France	Hospitalier de la Rochelle-Ré-Aunis	La Rochelle
France	CHRU de Lille - Hopital Claude-Huriez	Lille
France	Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes	Marseille
France	CHU Montpellier	Montpellier
France	Hôpital Necker Service d'Hématologie Adult	Paris
France	Hostpial Saint Louis - CIRCO (Centre d'Investigations et de Recherche Clinique en Oncologie)	Paris
France	Pitié-Salpêtrière Hospital	Paris
France	CHU Lyon Sud	Pierre-Bénite	Lyon
France	Centre Henri Becquerel	Rouen
Germany	Uniklinik Aachen Klinik für Hämatologie, Onkologie, Hämostaseologie und Stammzelltransplantation	Aachen
Germany	HELIOS Klinikum Bad Saarow	Bad Saarow
Germany	Charite Universitatsmedizin Berlin (Benjamin Franklin Campus)	Berlin
Germany	Charite Universitatsmedizin Berlin (Virchow Campus)	Berlin
Germany	Ev. Diakonie-Krankenhaus gGmbH	Bremen
Germany	Gemeinschaftspraxis Haematologie and Onkologie-Dresden	Dresden
Germany	Martin-Luther-University Halle-Wittenberg Department of Oncology	Halle
Germany	Medizinische Hochschule	Hannover
Germany	Universität Heidelberg Medizinische Klinik V Hämatologie, Onkologie und Rheumatologie	Heidelberg
Germany	Klinikum Kempten Klinik für Innere Medizin III - Hämatologie, Onkologie und Palliativmedizin	Koln
Germany	Klinikum Leverkusen	Leverkusen
Germany	Klinikum Ludwigshafen	Ludwigshafen
Germany	Rotkreuzklinikum München	Muenchen
Germany	Klinikum Nürnberg Nord	Nuernberg
Greece	Hematology Clinic,General Hospital of Athens,G. Gennimatos	Athens
Greece	Hematology Department Laiko General Hospital	Athens
Greece	National & Kapodistrian University of Athens, Laiko General Hospital	Athens
Greece	Second Depth of Internal Medicine, Attiko University Hospital	Athens
Greece	National & Kapodistrian University of Athens, Attiko University Hospital	Chaidari
Greece	Haematology Department and HCT Unit G.Papanicolaou Hospital	Exochi	Thessaloniki
Greece	Department of clinical hematology ,university hospital Ioannina	Ioánnina
Greece	University of Patras Medical School	Patras
Hungary	Országos Onkológiai Intézet "A" Belgyógyászati Onkológiai Osztály	Budapest
Hungary	Semmelweis Egyetem Általános Orvosi Kar	Budapest
Hungary	Semmelweis University Department of Medicine and Oncology	Budapest
Hungary	Somogy Megyei Kaposi Mór Oktató Kórház	Kaposvár
Hungary	Pécsi Tudományegyetem, ÁOK, I. számú Belgyógyászati Klinika	Pécs
Hungary	CSolnoky ferenc Hospital	Veszprém
Hungary	Veszprém Megyei Csolnoky Ferenc Kórház	Veszprém
India	Institute of Medical Sciences & SUM Hospital	Bhubaneswar	Odisha
India	Cancer Institute (WIA)	Chennai	Tamil Nadu
India	Saveetha Medical College Hospital	Chennai	Tamil Nadu
India	G. Kuppu Swamy Naidu Hospital	Coimbatore	Tamil Nadu
India	IRCH, All India Institute of Medical Sciences	Delhi
India	Netaji Subhas Chandra Bose Cancer Research Hospital	Kolkata	West Bengal
India	Netaji Subhas Chandra Bose Cancer Research Institute	Kolkata	West Bengal
India	Nil Ratan Sircar Medical College and Hospital	Kolkata	West Bengal
India	TATA Memorial Centre	Kolkata	West Bengal
India	King George's Medical University (KGMU)	Lucknow	Uttar Pradesh
India	Dayanand Medical College and Hospital	Ludhiana	Punjab
India	Meenakshi Mission Hospital & Research Centre	Madurai	Tamil Nadu
India	Jaslok Hospital and Research Centre	Mumbai	Maharashtra
India	Prince Aly Khan Hospital	Mumbai	Maharashtra
India	Dr. B.R.A. Institute Rotary Cancer Hospital All India Institute of Medical Sciences	New Delhi
India	Rajiv Gandhi Cancer Hospital	New Delhi	Delhi
India	Regional Cancer Centre, IGIMS	Patna	Bihar
India	Deenanath Mangeshkar Hospital	Pune	Maharashtra
India	Regional Cancer Centre	Thiruvananthapuram	Kerala
India	SRM Institutes for Medical Science	Vadapalani	Chennai
Israel	Hematology-Soroka	Beer Sheva
Israel	Rambam Healthcare Campus	Haifa
Israel	Wolfson MC	Holon
Israel	Hadassah Medical Center	Jerusalem
Israel	Rabin Medical Center	Petach Tikva
Israel	Assuta Medical Center	Tel Aviv
Israel	TLV Sorasky Medical Center	Tel Aviv
Israel	Sheba Medical Center	Tel Hashomer
Italy	Instituto di Ematologia Seragnoli Pad 8 Universita di Bologna	Bologna
Italy	AOU Maggiore della Carità SCDU Ematologia	Florence
Italy	SODc Ematologica ,AOU Careggi	Florence
Italy	Hematology-Oncology & Stem Cell Transplantation Unit, National Cancer Institute, Fondazione 'G. Pascale', IRCCS	Naples
Italy	SCDU Ematologia, Division of Hematology, Dept. of Translational Medicine, Universita del Piemonte Orientale	Novara
Italy	Fondazione Policlinico Universitario A. Gemelli	Rome
Italy	Azienda Ospedaliero-Universitaria Senese	Siena
Italy	Città della Salute e della Scienza di Torino	Torino
Netherlands	VUMc (Vrije Universiteit Amsterdam)	Amsterdam
Netherlands	LUMC (leidse universitair medisch centrum)	Leiden
New Zealand	North Shore Hospital	Auckland
New Zealand	Christchurch Hospital	Christchurch
Poland	Szpitale Wojewódzkie w Gdyni, Gdynskie Centrum onkologii	Gdynia
Poland	MCM (Malopolskie Centrum Medyczne)	Krakow
Poland	Wojewodzki Szpital Specjalistyczny w Legnicy	Legnica
Poland	Memorial Provincial Specialist Hospital in Lodz	Lódz
Poland	Hematology Department St John's Cancer Centre	Lublin
Poland	Samodzielny Publiczny Szpital Kliniczny nr 1 w Lublinie	Lublin
Poland	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Ministerstwa	Olsztyn
Poland	Centrum Onkologii- Insytut Im. Marii Sklodowskiej-Curie Klinika Nowotworow Ukladu Chlonnego	Warszawa
Poland	Instytut Hematologii i Transfuzjologii	Warszawa
Poland	Maria Sklodowska Curie National Research Institute	Warszawa
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza	Wroclaw	Radeckiego
Serbia	Institut za onkologiju i radiologiju Srbije	Belgrade
Serbia	Klinicki centar Srbije Klinika za hematologiju	Belgrade
Serbia	Klinicko Bolnick Centar Zemun Odeljenje hematologije	Belgrade
Serbia	Klinicko bolnicki centar Zvezdara	Belgrade
Serbia	Klinicki centar Niš Klinika za hematologiju	Nis
Serbia	Institut za onkologiju Vojvodine	Sremska Kamenica
Spain	Hospitla Universitari Germans Trias i Pujol - ICO	Badalona
Spain	Hospital Clinic i Provincial de Barcelona	Barcelona
Spain	Hospital University Vall d'Hebron	Barcelona
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital de Son Llàtzer	Palma de Mallorca
Spain	Clínica Universidad De Navarra	Pamplona
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Virgen del Rocio	Sevilla
United Kingdom	Addenbrooke's Hospital Cambridge	Cambridge
United Kingdom	Gloucestershire Royal Hospital	Gloucester	Gloucestershire
United Kingdom	Northwick Park Hospital	Harrow	Middlesex
United Kingdom	Leeds Teaching Hospitals NHS Trust	Leeds	Yorkshire
United Kingdom	Royal Liverpool University Hospital	Liverpool
United Kingdom	The Clatterbridge Cancer Centre NHS Foundation Trust	Liverpool
United Kingdom	Guy's and St Thomas' NHS Foundation Trust	London
United Kingdom	King's College Hospital	London
United Kingdom	Princess Royal University Hospital (PRUH)	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Oxford University Hospitals NHS Trust Oxford Cancer and Haematology Centre, Churchill Hospital	Oxford
United Kingdom	Derriford Hospital	Plymouth
United Kingdom	Southampton University Hospital	Southampton	Hampshire
United Kingdom	Royal Marsden Hospital	Sutton	London
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Tufts Medical Center	Boston	Massachusetts
United States	Lahey Clinic	Burlington	Massachusetts
United States	Gabrail Cancer Center	Canton	Ohio
United States	Robert H. Lurie Comprehensive Cancer Center/Northwestern University	Chicago	Illinois
United States	University of Chicago	Chicago	Illinois
United States	Cleveland Clinic Foundation	Cleveland	Ohio
United States	University Hospitals Seidman Cancer Center	Cleveland	Ohio
United States	Greenville Hospital System	Greenville	South Carolina
United States	John Theurer Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey
United States	MD Anderson	Houston	Texas
United States	Clinical Research Alliance	Lake Success	New York
United States	Norton Cancer Institute	Louisville	Kentucky
United States	New York Presbyterian Hospital/ Cornell Medical College	New York	New York
United States	University of Oklahoma	Oklahoma City	Oklahoma
United States	Boca Raton Cancer Research Medical Center	Plantation	Florida
United States	University of California San Francisco	San Francisco	California
United States	University of California Los Angeles (UCLA)	Santa Monica	California
United States	Swedish Cancer Institute	Seattle	Washington
United States	Virginia Mason Hospital & Medical Center	Seattle	Washington
United States	Stony Brook University Hospital	Stony Brook	New York
United States	UACC Arizona	Tucson	Arizona
United States	University of Massachusetts Medical School	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Karyopharm Therapeutics Inc

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Bulgaria,  Canada,  France,  Germany,  Greece,  Hungary,  India,  Israel,  Italy,  Netherlands,  New Zealand,  Poland,  Serbia,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Overall Response Rate (ORR)	Assessed according to the revised response criteria based on the Guidelines of the International Working Group (IWG).	One year
Primary	Part 2: Overall Response Rate (ORR) Based on Lugano Criteria	Assessed according to the response assessment of lymphoma based on Lugano classification.	From initial randomization until date of disease progression or death (maximum of 1 year from Part 2 randomization)
Secondary	Part 1: Duration of Response (DOR)		From time of first response until disease progression or death (maximum of 1 year from Part 1 randomization)
Secondary	Part 1: Disease Control Rate (DCR)		From initial response until disease progression or death (maximum of 1 year from Part 1 randomization)
Secondary	Part 1: Number of Participants with Treatment-emergent Adverse Events (TEAEs)		From Baseline up to 30 days after last dose (maximum of 1 year from Part 1 randomization)
Secondary	Part 1: Number of Participants with Eastern Cooperative Oncology Group (ECOG) Performance Status		From Baseline up to 30 days after last dose (maximum of 1 year from Part 1 randomization)
Secondary	Part 2: Duration of response (DOR)		From time of first response (Part 2) until disease progression or death (maximum of 1 year from Part 2 randomization)
Secondary	Part 2: Disease control rate (DCR)		From initial response (Part 2) until disease progression or death (maximum of 1 year from Part 2 randomization)
Secondary	Part 2: Overall Response Rate (ORR) Based on Modified Lugano Criteria		From initial randomization until date of disease progression or death (maximum of 1 year from Part 2 randomization)
Secondary	Part 2: Number of Participants with Treatment-emergent Adverse Events		From Baseline up to 30 days after last dose (maximum of 1 year from Part 2 randomization)
Secondary	Part 2: Number of Participants with Eastern Cooperative Oncology Group (ECOG) Performance Status		From Baseline up to 30 days after last dose (maximum of 1 year from Part 2 randomization)