Study of LOXO-305 Versus Investigator's Choice (IdelaR or BR) in Patients With Previously Treated Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

Chronic Lymphocytic Leukemia Clinical Trial

— BRUIN CLL-321  

Official title:

A Phase 3 Open-Label, Randomized Study of LOXO-305 Versus Investigator's Choice of Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in BTK Inhibitor Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-321)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04666038
• Other study ID #: LOXO-BTK-20020
• Secondary ID: J2N-OX-JZNN
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: March 9, 2021
• Est. completion date: May 2027

Study information

• Verified date: April 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a study for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) who have previously received treatment with at least a BTK inhibitor. The main purpose is to compare LOXO-305 to idelalisib plus rituximab or bendamustine plus rituximab. Participation could last up to four years, and possibly longer, if the disease does not progress.

Description:

This is a Phase 3 global, randomized, open-label study comparing LOXO-305 (Arm A) to investigator's choice of either idelalisib plus rituximab or bendamustine plus rituximab (Arm B) in CLL/SLL patients who have been treated with at least a covalent BTK inhibitor (BTKi). Patients may have discontinued the prior covalent BTKi due to disease progression (PD) or intolerance. Patients who have received venetoclax are eligible for the study. Eligible patients will be randomized in 1:1 to Arm A and Arm B.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 250
• Est. completion date: May 2027
• Est. primary completion date: November 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Confirmed diagnosis of CLL/SLL requiring therapy as defined by iwCLL 2018 criteria.

• Previously treated with a covalent BTK inhibitor.

• Eastern Cooperative Oncology Group (ECOG) 0-2.

• Absolute neutrophil count = 0.75 × 10^9/L without granulocyte-colony-stimulating factor support, or = 0.50 × 10^9/L in patients with documented bone marrow involvement considered to impair hematopoiesis. Granulocyte-colony-stimulating factor support is permitted in patients with documented bone marrow involvement.

• Hemoglobin = 8 g/dL or = 6 g/dL in patients with documented bone marrow involvement considered to impair hematopoiesis. Transfusion support is permitted in patients with bone marrow involvement.

• Platelets = 50 × 10^9/L. If an investigator has chosen bendamustine/rituximab as the Arm B treatment, platelets must be = 75 × 10^9/L. Patients may enroll below these thresholds if the Investigator determines the cytopenia is related to bone marrow involvement considered to impair hematopoiesis. Patients with a platelet count < 30 x 10^9/L are excluded.

• AST and ALT = 3.0 x upper limit of normal (ULN).

• Total bilirubin = 1.5 x ULN.

• Estimated creatinine clearance of = 30 mL/min.

Exclusion Criteria:

• Known or suspected Richter's transformation at any time preceding enrollment.

• Known or suspected history of central nervous system (CNS) involvement by CLL/SLL.

• Ongoing drug-induced liver injury.

• Active uncontrolled auto-immune cytopenia.

• Significant cardiovascular disease.

• History of allogeneic or stem cell transplantation (SCT) or chimeric antigen receptor-modified T cells (CAR-T) therapy within the past 60 days.

• Active hepatitis B or hepatitis C.

• Known active cytomegalovirus (CMV) infection.

• Active uncontrolled systemic bacterial, viral, fungal or parasitic infection.

• Known Human Immunodeficiency Virus (HIV) infection, regardless of CD4 count.

• Clinically significant active malabsorption syndrome or inflammatory bowel disease

• Prior exposure to non-covalent (reversible) BTK inhibitor.

• Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist.

• Current treatment with strong cytochrome P450 (CYP) 3A4 (CYP3A4) inhibitors or inducers.

• Vaccination with a live vaccine within 28 days prior to randomization.

• Patients with the following hypersensitivity:

1. Known hypersensitivity, including anaphylaxis, to any component or excipient of LOXO-305. For patients planned to receive idelalisib, known hypersensitivity, including anaphylaxis, to any component or excipient of idelalisib. For patients planned to receive bendamustine, known hypersensitivity, including anaphylaxis, to any component or excipient of bendamustine.

2. Prior significant hypersensitivity to rituximab.

Related Conditions & MeSH terms

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

Intervention

Drug:
• LOXO-305
Oral LOXO-305
• Idelalisib
Oral
• Bendamustine
IV
• Rituximab
IV

Locations

Country	Name	City	State
Australia	St Vincent's Hospital	Darlinghurst	New South Wales
Australia	Canberra Hospital	Garran	Australian Capital Territory
Australia	The St. George Hospital	Kogarah	New South Wales
Australia	Ingham Institute of Medical Research	Liverpool	New South Wales
Australia	The Alfred Hospital	Melbourne	Victoria
Australia	Royal Perth Hospital	Perth	Western Australia
Australia	Westmead Hospital	Wentworthville	New South Wales
Austria	Ordensklinikum Linz GmbH Elisabethinen	Linz	Oberösterreich
Austria	Uniklinikum Salzburg	Salzburg	Osterreich
Austria	Medizinische Universität Wien	Wien
Belgium	Universitair Ziekenhuis Gent	Gent
Belgium	Groupe Jolimont	Haine-Saint-Paul
Belgium	AZ St-Elisabeth	Herentals
Belgium	Clinique Saint Pierre Ottignies	Ottignies
Belgium	AZ Delta	Roeselare	West Flanders
Belgium	VITAZ	Sint-Niklaas	Oost-Vlaanderen
Belgium	CHR Verviers-Onco	Verviers	Liege
Canada	Queen Elizabeth II Health Sciences Center	Halifax	Nova Scotia
Canada	Southlake Regional Health Centre	Newmarket	Ontario
Canada	Princess Margaret Hospital (Ontario)	Toronto	Ontario
Canada	Cancer Care Manitoba	Winnipeg	Manitoba
China	Beijing Hospital	Beijing
China	Peking University First Hospital	Beijing	Beijing
China	Peking University Third Hospital	Beijing	Beijing
China	Hunan Cancer Hospital	Changsha	Hunan
China	Southern Medical University Nanfang Hospital	Guangzhou	Guangdong
China	Sun Yat-sen University Cancer Center	Guangzhou	Guangdong
China	Hainan Province People's Hospital	Haikou	Hainan
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Gansu Province Cancer Hospital	Lanzhou	Gansu
China	Zhejiang Provincial Taizhou Hospital	Linhai	Zhejiang
China	The First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	The Second Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Fudan University Shanghai Cancer Center	Shanghai
China	Shanghai Jiaotong University School of Medicine Ruijin Hospital	Shanghai
China	Blood Institute of the Chinese Academy of Medical science	Tianjin
China	Tianjin Medical University Cancer Institute and Hospital	Tianjin	Tianjin
China	Affiliated Tumor Hospital of Xinjiang Medical University	Ürümqi	Xinjiang
China	Xuanwu Hospital Capital Medical University	Xicheng District	Beijing
China	The Affiliated Hospital of Xuzhou Medical College	Xuzhou	Jiangsu
China	Henan Cancer Hospital	Zhengzhou	Henan
Croatia	University Hospital Split	Split
Croatia	Division of Hematology, Dept. of Internal Medicine, University Hospital Centre Zagreb	Zagreb
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
France	Centre Hospitalier de la Côte Basque	Bayonne
France	Hospital AVICENNE	Bobigny	Cedex
France	Institut Bergonié - Centre Régional de Lutte Contre Le Cancer de Bordeaux et Sud Ouest	Bordeaux
France	CHRU de Brest - Hôpital Morvan	Brest cedex
France	CHU De Grenoble Hopital Albert Michallon	Grenoble	Cedex 09
France	CHD Vendee	La Roche-sur-Yon	La Roche Sur Yon
France	Centre Hospitalier du Mans	Le Mans
France	Hopital Saint Vincent De Paul	Lille cedex
France	Chu Nimes/Institut De Cancerologie Du Gard	Nîmes	Nimes
France	Ch Perpignan	Perpignan
France	Centre Hospitalier Lyon Sud	Pierre Benite	Cedex
France	Pole Regionalde Cancérologie(CHU de Poitiers)	Politiers
France	Centre de Lutte Contre le Cancer - Centre Henri Becquerel Normandie Rouen	Rouen	Seine-Maritime
France	CHRU De Tours	Tours	Tours Cedex 9
Germany	Charité Campus Virchow-Klinikum	Berlin
Germany	Universitätsklinikum Heidelberg	Heidelberg	Baden-Württemberg
Germany	Uniklinik Köln	Kerpener	Köln
Germany	Universitätsklinikum Schleswig-Holstein	Kiel	Schleswig-Holstein
Germany	München Klinik Schwabing	Koelner Platz 1	München
Germany	Universitätsmedizin Mainz III. Medizinische Klinik und Poliklinik	Langenbeckstraße 1	Mainz
Germany	Lübecker Onkologische Schwerpunktpraxis	Lübeck	Schleswig-Holstein
Germany	Universitätsklinikum Ulm	Ulm	Baden-Württemberg
Hungary	Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen
Hungary	SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz	Nyiregyhaza
Hungary	University of Pecs 1st. Internalmedicin Clinic Dept	Pecs
Ireland	Beaumont Hospital, Dublin	Dublin
Ireland	Mater Misericordiae Hospital	Dublin 7
Ireland	St James's Hosptial	Dublin 8
Israel	Soroka Medical Center	Beer Sheva
Israel	Carmel Hospital	Haifa	?eifa
Israel	Laniado Medical Center	Netanya
Israel	Rabin Medical Center	Petah Tikva	HaMerkaz
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
Italy	Azienda Ospedaliera Nazionale Santi Antonio e Biagio e Cesare Arrigo	Alessandria
Italy	Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII	Bergamo
Italy	ASST Spedali Civili - Università degli Studi	Brescia
Italy	A.O.U. Policlinico G.Rodolico - S. Marco	Catania
Italy	Azienda Ospedaliera Pugliese Ciaccio	Catanzaro
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze
Italy	IRCCS Ospedale Policlinico San Martino	Genova
Italy	Ospedale Papardo	Messina
Italy	ASST Grande Ospedale Metropolitano Niguarda Comitato Etico Milano Area C	Milano
Italy	IRCCS Ospedale San Raffaele	Milano
Italy	A.O.U. di Modena	Modena
Italy	ASST-Monza -U.O Ematologia Adulti	Monza (MB) -Settore E	Piano 2
Italy	Fondazione IRCCS Policlinico San Matteo	Pavia
Italy	Istituto di Ematologia-C.R.E.O. (Centro di Ricerche Emato-Oncologich)	Perugia
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa	PI
Italy	Ospedale Santa Maria delle Croci	Ravenna
Italy	Irccs Crob	Rionero In Vulture	Potenza
Italy	Fondazione Policlinico Universitario Agostino Gemelli IRCCS - Università Cattolica del Sacro Cuore	Roma
Italy	Azienda Ospedaliera Santa Maria Terni	Terni
Italy	A.O.U. Citta' della Salute e della Scienza di Torino	Torino
Italy	Az. Osp. "Card G Panico"	Tricase
Italy	Azienda Sanitaria Universitaria Giuliano Isontina	Trieste
Italy	Ospedale Policlinico Giambattista Rossi, Borgo Roma	Verona
Italy	Irccs Istituto Tumori Giovanni Paolo Ii	Viale Orazio Flacco	Bari
Italy	AULSS8 Berica-Ospedale S.Bortolo	Vicenza	Veneto
Japan	JCHO Kyushu Hospital	Fukoka-ken
Japan	Tokai University Hospital- Isehara Campus	Isehara	Kanagawa
Japan	Saitama Medical Center	Kawagoe	Saitama
Japan	Kobe City Medical Center General Hospital	Kobe	Hyogo
Japan	Japanese Foundation for Cancer Research	Koto	Tokyo
Japan	Kumamoto University Hospital	Kumamoto
Japan	Aichi Cancer Center Hospital	Nagoya	Aichi
Japan	Nagoya City University Hospital	Nagoya	Aichi
Japan	Nagoya Medical Center	Nagoya	Aichi
Japan	Kochi Medical School Hospital	Nankoku	Kochi
Japan	Ogaki Municipal Hospital	Ogaki-shi	Gifu
Japan	Okayama University Hospital	Okayama
Japan	Osaka University Hospital	Osaka
Japan	Kindai University Hospital	Osaka Sayama-shi	Osaka
Japan	Hokkaido University Hospital	Sapporo	Hokkaido
Japan	NHO Sendai Medical Center	Sendai-shi	Miyagi-Ken
Japan	Tohoku University Hospital	Sendai-shi	Miyagi
Japan	NTT Medical Center Tokyo	Shinagawa-Ku	Tokyo
Korea, Republic of	Inje Univ Busan Paik Hospital	Busan
Korea, Republic of	Pusan National University Hospital	Busan	Pusan-Kwangyokshi
Korea, Republic of	Gachon University Gil Hospital	Namdong-gu	Incheon-gwangyeoksi [Incheon]
Korea, Republic of	The Catholic University of Korea-Seoul St. Mary's Hospital	Seocho-Gu	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul	Seoul, Korea
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul	Seoul-teukbyeolsi [Seoul]
Poland	Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im.ks.B.Markiewicza	Brzozów
Poland	Szpital Uniwersytecki nr 2 im. dr Jana Biziela w BydgoszczyKlinika Hematologii	Bydgoszcz
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk	Pomorskie
Poland	Szpitale Pomorskie Sp. z o. o.	Gdynia	Pomorskie
Poland	Wojewodzki Szpital Specjalistyczny	Iwaszkiewicza 5	Legnica
Poland	Pratia Onkologia Katowice	Katowice
Poland	Pratia MCM Krakow	Krakow
Poland	Wojewódzkie Wielospecjalistyczne Centrum Onkologii i Traumatologii	Lódz
Poland	Centrum Onkologii Ziemi Lubelskiej	Lublin	Lubelskie
Poland	Oddzial Hematologiczny, Specjalistyczny Szpital im. dra Sokolowskiego w Walbrzychu	Walbrzych
Poland	Instytut Hematologii i Transfuzjologii	Warszawa
Poland	Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy	Warszawa
Poland	Uniwersytecki Szpital Kliniczny Klinika	Wroclaw
Russian Federation	Budgetary Healthcare Institution of Omsk Region "Clinical Oncology Dispensary"	Omsk	Omskaya Oblast'
Russian Federation	Academician I.P. Pavlov First St-Petersburg State Medical University	Saint Petersburg
Russian Federation	Federal State Budgetary Institution "Russian Scientific and Research Institute of Hematology and Transfusiology of Federal Medico-Biological Agency	Saint Petersburg
Russian Federation	Oncology Dispensary #2 of Krasnodar Region	Sochi
Singapore	Gleneagles Medical Centre	Singapore	Central Singapore
Spain	Hospital General de Albacete	Albacete
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital San Pedro de Alcántara	Caceres
Spain	Hospital Duran I Reynals	Hospitalet De Llobregat	Barcelona
Spain	Hospital General Universitario Gregorio Marañón	Madrid	Planta Baja
Spain	Hospital Universitario Infanta Leonor-INTERNAL MED	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid	Madrid, Comunidad De
Spain	Hospital Universitario Quironsalud Madrid	Pozuelo De Alarcón	Madrid
Spain	Hospital Universitario Marques De Valdecilla	Santander
Spain	Complejo Hospitalario Universitario de Santiago de Compostel	Santiago de Compostela	La Coruna
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Universitario de Toledo	Toledo	Castilla La Mancha
Spain	Hospital Universitario de Alava	Vitoria
Switzerland	Clinica di Ematologia IOSI, Ospedale Bellinzona e Valli, Ente Ospedaliero Cantonale	Bellinzona	Svizzera
Taiwan	China Medical University Hospital	Taichung City	Taichung
Taiwan	Taipei Veterans General Hospital	Taipei City
Taiwan	Tri-Service General Hospital	Taipei City	Taipei
Taiwan	Chang Gung Memorial Hospital - Linkou	Taoyuan, (r.o.c.)
Turkey	Gazi University Faculty of Medicine	Ankara	Yenimahalle
Turkey	Istanbul University Istanbul Medicine Faculty	Faith	Istanbul
Turkey	Dokuz Eylul University Faculty of Medicine	Izmir
Turkey	Ege University Medical Faculty	Izmir
Turkey	Erciyes University Faculty of Medicine	Kayseri	Melikgazi
Turkey	Ankara University Medicine Hospital	Mamak	Ankara
United Kingdom	Aberdeen Royal Infirmary	Aberdeen	Aberdeen City
United Kingdom	Castle Hill Hospital	Cottingham	East Yorkshire
United Kingdom	Western General Hospital	Edinburgh	Scotland
United Kingdom	St James's University Hospital	Leeds
United Kingdom	St Johns Hospital at Howden	Livingston	West Lothian
United Kingdom	University College London Hospitals	London	Greater London
United Kingdom	Milton Keynes University Hospital	Milton Keynes
United Kingdom	GenesisCare Cambridge	Newmarket
United Kingdom	Norfolk and Norwich Hospital	Norwich	Norfolk
United Kingdom	Derriford Hospital	Plymouth	Devon
United Kingdom	Royal Marsden Hospital	Sutton	Surrey
United Kingdom	Singleton Hospital	Swansea	Sa2 8qa
United Kingdom	The Royal Cornwall Hospital	Truro	Cornwall
United States	Texas Oncology - Amarillo	Amarillo	Texas
United States	Saint Joseph Mercy Hospital	Ann Arbor	Michigan
United States	Rocky Mountain Cancer Center	Aurora	Colorado
United States	Texas Oncology Cancer Center	Austin	Texas
United States	Greenebaum Comprehensive Cancer Center	Baltimore	Maryland
United States	St. Vincent Frontier Cancer Center	Billings	Montana
United States	Boca Raton Regional Hospital	Boca Raton	Florida
United States	New Jersey Center for Cancer Research	Brick	New Jersey
United States	Rush University Medical Center	Chicago	Illinois
United States	Oncology Hematology Care Inc	Cincinnati	Ohio
United States	Texas Oncology - Dallas Presbyterian Hospital	Dallas	Texas
United States	Texas Oncology - Medical City Dallas	Dallas	Texas
United States	Southern Cancer Center, P.C.	Daphne	Alabama
United States	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon
United States	Brooke Army Medical Center	Fort Sam Houston	Texas
United States	Texas Oncology Fort Worth	Fort Worth	Texas
United States	The Center for Cancer and Blood Disorders	Fort Worth	Texas
United States	Orange Coast Memorial Medical Center	Fountain Valley	California
United States	Virginia Cancer Specialists, PC	Gainesville	Virginia
United States	Palo Verde Hematology Oncology	Glendale	Arizona
United States	Ascension St. John Hospital	Grosse Pointe Woods	Michigan
United States	Community Health Network	Indianapolis	Indiana
United States	Cancer Specialists of North Florida -St Augustine	Jacksonville	Florida
United States	Arnett Cancer Center	Lafayette	Indiana
United States	University of Kentucky Markey Cancer Center	Lexington	Kentucky
United States	Nebraska Hematology-Oncology	Lincoln	Nebraska
United States	California Research Institute	Los Angeles	California
United States	Norton Cancer Institute	Louisville	Kentucky
United States	University of Wisconsin Carbone Cancer Center	Madison	Wisconsin
United States	WellStar Health System	Marietta	Georgia
United States	Texas Oncology - McAllen	McAllen	Texas
United States	Mitchell Cancer Institute -University of South Alabama	Mobile	Alabama
United States	Cancer Center Office of Clinical Research	New Orleans	Louisiana
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Medical Oncology Hematology Consultants, PA	Newark	Delaware
United States	Illinois Cancer Specialists-Niles	Niles	Illinois
United States	Mercy Health-Paducah Medical Oncology and Hematology	Paducah	Kentucky
United States	Oncology and Hematology Associates of Southwest Virginia Inc	Roanoke	Virginia
United States	University of Rochester	Rochester	New York
United States	Carolina Blood and Cancer Care Associates	Rock Hill	South Carolina
United States	Minnesota Oncology/Hematology PA	Saint Paul	Minnesota
United States	Texas Oncology - San Antonio Medical Center	San Antonio	Texas
United States	Northwest Medical Specialties, PLLC	Tacoma	Washington
United States	Oncology-Hematology Associates of West Broward	Tamarac	Florida
United States	Arizona Oncology Associates, P.C. - HOPE	Tucson	Arizona
United States	Clinical Research Alliance, Inc.	Westbury	New York

Sponsors (2)

Lead Sponsor	Collaborator
Loxo Oncology, Inc.	Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  China,  Croatia,  Czechia,  France,  Germany,  Hungary,  Ireland,  Israel,  Italy,  Japan,  Korea, Republic of,  Poland,  Russian Federation,  Singapore,  Spain,  Switzerland,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To evaluate progression-free survival (PFS) of LOXO-305 monotherapy (Arm A) compared to investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR) (Arm B)	Assessed per iwCLL 2018	Up to approximately 36 months
Secondary	To evaluate the effectiveness of Arm A compared to Arm B based on Overall Response Rate (ORR)	Assessed per iwCLL 2018	Up to approximately 36 months
Secondary	To evaluate the effectiveness of Arm A compared to Arm B based on Overall Survival (OS)	Assessed by survival	Up to approximately 36 months
Secondary	To evaluate the effectiveness of Arm A compared to Arm B based on Time to Next Treatment (TTNT)	Defined as time from randomization to next systemic anticancer therapy for CLL/SLL	Up to approximately 36 months
Secondary	Time to worsening (TTW) of CLL/SLL related symptoms	Using symptom questions identified from the EORTC item library. The range of raw scores for these items could be from 0 to 52 with highest score being worse symptoms	Up to approximately 36 months
Secondary	Time to worsening (TTW) of physical function	Using the 5 physical function items identified from the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) questionnaire (also known as the EORTC IL 19 questionnaire), physical function will be measured. The range of raw scores for these items could be from 0-20 with the highest score indicating worst function.	Up to approximately 36 months