Clinical trial NCT01987505: MabRella Study: A Study to Evaluate the Safety of Switching From Intravenous to Subcutaneous Administration of Rituximab During First-Line Treatment for Lymphoma
Official title: Open Label, Single-arm, Phase IIIb Clinical Trial to Evaluate the Safety of Switching From Intravenous Rituximab to Subcutaneous Rituximab During First Line Treatment for CD20+ Non-Hodgkin's Follicular Lymphoma and Diffuse Large B-cell Lymphoma.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Lymphoma, Non Hodgkin
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2013-11-19
Enrollment: 140
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This open-label, single-arm, phase IIIb study will evaluate the safety of switching from intravenous (IV) to subcutaneous (SC) administration of rituximab during first-line treatment for participants with CD20+ non-Hodgkin's follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL) who have already received at least one full dose of rituximab IV. Participants with FL will be given 1400 mg rituximab SC during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). 1400 mg SC of rituximab will be given to participants with DLBCL once monthly for 4-7 cycles. Treatment duration is expected to last up to 7 months for participants with DLBCL and up to 32 months for participants with FL.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 and ≤ 80 years at time of enrolment.
* Life expectancy ≥ 6 months.
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 3.
* Fertile men or women of childbearing potential must use effective contraception until at least 12 months after the last dose; women must not be pregnant.
* Histologically confirmed CD20+ diffuse large B-cell lymphoma (DLBCL) or CD20+ follicular Non-Hodgkin Lymphoma (FL) grade 1, 2 or 3a according to the World Health Organisation Classification system.

Induction only:

* Participants with Follicular Lymphoma should meet Groupe D'Etude des Lymphomes Folliculaires (GELF) criteria to initiate treatment.
* At least tumor \>/= 1.5 cm as measured by computed tomography (CT) scan.

FL treatment-related criteria

- Currently being treated with rituximab IV during first-line therapy and has received at least one full dose of rituximab IV.

Exclusion Criteria:

* Transformed lymphoma.
* Primary central nervous system lymphoma, primary effusion lymphoma, primary mediastinal DLBCL, DLBCL of the testis, primary cutaneous DLBCL or histologic evidence of transformation to a Burkitt lymphoma.
* History of other cancer, including one that has been treated but not with curative intent, unless the cancer has been in remission without treatment for \>/= 5 years prior to dosing. Note: Participants with a history of cured skin cancer or in situ carcinoma of the cervix are eligible for the study.
* Ongoing corticosteroid use \> 30 mg/day of prednisone or equivalent. Note: Participants receiving corticosteroid treatment with \</= 30 mg/day of prednisone or equivalent must be on a stable regimen for at least 4 weeks prior to start of dosing.
* Inadequate renal, hematologic, or hepatic function.
* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or known sensitivity or allergy to murine products.
* For participants with DLBCL: Contraindication to any of the individual components of CHOP (cyclophosphamide, vincristine, doxorubicin and prednisone), including prior anthracycline treatment.
* For participants with FL: contraindication to standard chemotherapy.
* Other serious underlying medical conditions.
* Recent major surgery (within 4 weeks prior to dosing), other than for diagnosis.
* Active and/or severe infections (excluding nail fungal infections) or any infection requiring treatment with IV antibiotics or hospitalization within 4 weeks prior to dosing.
* Active Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection. Note: Participants testing positive for Hepatitis B or C virus antibodies but with an undetectable viral load may be included.
* History of Human Immunodeficiency Virus (HIV) positive status.

Primary outcomes:
measure: Percentage of Participants With Administration-Associated Reactions (AARs)
timeFrame: From start of treatment to end of treatment (up to 32 months)
Secondary outcomes:
measure: Percentage of Participants With At Least One Grade >/= 3 Adverse Events (AEs)
timeFrame: From start of recruitment (10 months period) up to end of treatment at 32 months (total period up to 42 months)
measure: Percentage of Participants With At Least One Grade >/= 3 Infusion/ Injection Related Reactions (IIRRs)
timeFrame: From start of treatment to end of treatment (up to 32 months)
measure: Percentage of Participants With At Least One Serious Adverse Event (SAE)
timeFrame: From start of recruitment (10 months period) up to end of treatment at 32 months (total period up to 42 months)
measure: Event-Free Survival (EFS)
timeFrame: From time of first dose of rituximab IV before study enrollment up to end of study (up to approximately 62 months)
measure: Progression-Free Survival (PFS)
timeFrame: From time of first dose of rituximab IV before study enrollment up to end of study (up to approximately 62 months)
measure: Overall Survival (OS)
timeFrame: From time of first dose of rituximab IV before study enrollment up to end of study (up to approximately 62 months)
measure: Disease-Free Survival (DFS)
timeFrame: From time of first dose of rituximab IV before study enrollment up to end of study (up to approximately 62 months)
measure: Treatment Response Rate
timeFrame: 4-6 weeks after the last dose of Induction (Up to approximately 8 months)
Other outcomes:
Locations:
city: Vitoria
country: Spain
facility: Hospital De Txagorritxu; Servicio de Hematologia
state: Alava
city: Elda
country: Spain
facility: Hospital General de Elda; Servicio de Hematologia
state: Alicante
city: Granollers
country: Spain
facility: Hospital de Granollers, Servicio de Hematología
state: Barcelona
city: Terrassa
country: Spain
facility: Hospital Mutua de Terrassa; Servicio de Hematologia
state: Barcelona
city: Palma de Mallorca
country: Spain
facility: Hospital Son Llatzer; Servicio de Hematologia
state: Islas Baleares
city: La Coruna
country: Spain
facility: Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Hematologia
state: LA Coruña
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Hematologia
state: LA Coruña
city: Logroño
country: Spain
facility: Complejo Hospitalario San Millan - San Pedro; Servicio Hematologia
state: LA Rioja
city: León
country: Spain
facility: Complejo Asistencial de León, Servicio de Hematología
state: Leon
city: Fuenlabrada
country: Spain
facility: Hospital Universitario de Fuenlabrada; Servicio de Hematologia
state: Madrid
city: Leganes
country: Spain
facility: Hospital Severo Ochoa; Servicio de Hematologia
state: Madrid
city: Mostoles
country: Spain
facility: Hosital Universitario de Mostoles;Servicio de Hematologia
state: Madrid
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra; Servicio de Hematologia
state: Navarra
city: Pamplona
country: Spain
facility: Hospital de Navarra, Servicio de Hematología
state: Navarra
city: Vigo
country: Spain
facility: Complejo Hospitalario Universitario de Vigo; Servicio de Hematologia
state: Pontevedra
city: Santa Cruz de Tenerife
country: Spain
facility: Complejo Hospitalario Nuestra Señora de la Candelaria; Servicio de Oncologia
state: Tenerife
city: Bilbao
country: Spain
facility: Hospital de Basurto; Servicio de Hematologia
state: Vizcaya
city: Galdakao
country: Spain
facility: Hospital de Galdakano; Servicio de Hematologia
state: Vizcaya
city: Almeria
country: Spain
facility: Complejo Hospitalario Torrecardenas; Servicio de Hematologia
city: Burgos
country: Spain
facility: Hospital Universitario de Burgos, Servicio de Hematología
city: Castellon
country: Spain
facility: Hospital General de Castellon; Servicio de Hematologia
city: Cordoba
country: Spain
facility: Hospital Universitario Reina Sofia; Servicio de Hematologia
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves; Servicio de Hematologia
city: Guadalajara
country: Spain
facility: Hospital Universitario de Gaudalajara; Hematología
city: Lerida
country: Spain
facility: Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Hematologia
city: Madrid
country: Spain
facility: Hospital Infanta Leonor; Servicio de Hematologia
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz; Servicio de Hematologia
city: Madrid
country: Spain
facility: Hospital Universitario Clínico San Carlos; Servicio de Hematología
city: Madrid
country: Spain
facility: HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio Hematologia
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro; Servicio de Hematologia
city: Madrid
country: Spain
facility: Hospital Universitario Principe de Asturias; Servicio de Hematología
city: Malaga
country: Spain
facility: Hospital Univ. Virgen de la Victoria
city: Murcia
country: Spain
facility: Hospital General Universitario J.M Morales Meseguer; Servicio de Hematología
city: Murcia
country: Spain
facility: Hospital Universitario Virgen de Arrixaca; Servicio de Hematologia
city: Pontevedra
country: Spain
facility: Complejo Hospitalario de Pontevedra; Servicio de Hematologia
city: Segovia
country: Spain
facility: Complejo Asistencial de Segovia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena; Servicio de Hematologia
city: Sevilla
country: Spain
facility: Hospital Univ. Nuestra Señora de Valme; Servicio de Hematologia
city: Valladolid
country: Spain
facility: Hospital de Rio Hortega; Servicio de Hematologia
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Petrini M, Gaidano G, Mengarelli A, Consoli U, Santoro A, Liberati AM, Ladetto M, Fraticelli V, Guarini A, Mannina D, Ferrando P, Corradini P, Musto P, Stelitano C, Marino D, Camera A, Murineddu M, Battistini R, Caparrotti G, Turrini M, Arcaini L, Santini S, Cerqueti M, Ferreri AJM, Cantore N, Inzoli A, Cardinale G, Ronci B, La Nasa G, Massimi S, Gaglione G, Barbiero V, Martelli M. Safety and Efficacy of Subcutaneous Rituximab in Previously Untreated Patients with CD20+ Diffuse Large B-Cell Lymphoma or Follicular Lymphoma: Results from an Italian Phase IIIb Study. Adv Hematol. 2022 Jan 27;2022:5581772. doi: 10.1155/2022/5581772. eCollection 2022.
citation: Garcia-Munoz R, Quero C, Perez-Persona E, Domingo-Garcia A, Perez-Lopez C, Villaescusa-de-la-Rosa T, Martinez-Castro AM, Arguinano-Perez JM, Parra-Cuadrado JF, Panizo C. Safety of switching from intravenous to subcutaneous rituximab during first-line treatment of patients with non-Hodgkin lymphoma: the Spanish population of the MabRella study. Br J Haematol. 2020 Mar;188(5):661-673. doi: 10.1111/bjh.16227. Epub 2019 Oct 1.