MabRella Study: A Study to Evaluate the Safety of Switching From Intravenous to Subcutaneous Administration of Rituximab During First-Line Treatment for Lymphoma

Lymphoma, Non Hodgkin Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01987505
• Other study ID #: ML28943
• Secondary ID: 2013-001118-14
• Status: Completed
• Phase: Phase 3
• Start date: November 11, 2013
• Est. completion date: April 11, 2017

Study information

• Verified date: December 2018
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 140
• Est. completion date: April 11, 2017
• Est. primary completion date: April 11, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non Hodgkin
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• Rituximab
1400 mg will be injected subcutaneously (SC).

Locations

Country	Name	City	State
Spain	Complejo Hospitalario Torrecardenas; Servicio de Hematologia	Almeria
Spain	Hospital de Basurto; Servicio de Hematologia	Bilbao	Vizcaya
Spain	Hospital Universitario de Burgos, Servicio de Hematología	Burgos
Spain	Hospital General de Castellon; Servicio de Hematologia	Castellon
Spain	Hospital Universitario Reina Sofia; Servicio de Hematologia	Cordoba
Spain	Hospital General de Elda; Servicio de Hematologia	Elda	Alicante
Spain	Hospital Universitario de Fuenlabrada; Servicio de Hematologia	Fuenlabrada	Madrid
Spain	Hospital de Galdakano; Servicio de Hematologia	Galdakao	Vizcaya
Spain	Hospital Universitario Virgen de las Nieves; Servicio de Hematologia	Granada
Spain	Hospital de Granollers, Servicio de Hematología	Granollers	Barcelona
Spain	Hospital Universitario de Gaudalajara; Hematología	Guadalajara
Spain	Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Hematologia	La Coruna	LA Coruña
Spain	Hospital Severo Ochoa; Servicio de Hematologia	Leganes	Madrid
Spain	Complejo Asistencial de León, Servicio de Hematología	León	Leon
Spain	Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Hematologia	Lerida
Spain	Complejo Hospitalario San Millan - San Pedro; Servicio Hematologia	Logroño	LA Rioja
Spain	Fundacion Jimenez Diaz; Servicio de Hematologia	Madrid
Spain	HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio Hematologia	Madrid
Spain	Hospital Infanta Leonor; Servicio de Hematologia	Madrid
Spain	Hospital Universitario Clínico San Carlos; Servicio de Hematología	Madrid
Spain	Hospital Universitario Principe de Asturias; Servicio de Hematología	Madrid
Spain	Hospital Universitario Puerta de Hierro; Servicio de Hematologia	Madrid
Spain	Hospital Univ. Virgen de la Victoria	Malaga
Spain	Hosital Universitario de Mostoles;Servicio de Hematologia	Mostoles	Madrid
Spain	Hospital General Universitario J.M Morales Meseguer; Servicio de Hematología	Murcia
Spain	Hospital Universitario Virgen de Arrixaca; Servicio de Hematologia	Murcia
Spain	Hospital Son Llatzer; Servicio de Hematologia	Palma de Mallorca	Islas Baleares
Spain	Clinica Universitaria de Navarra; Servicio de Hematologia	Pamplona	Navarra
Spain	Hospital de Navarra, Servicio de Hematología	Pamplona	Navarra
Spain	Complejo Hospitalario de Pontevedra; Servicio de Hematologia	Pontevedra
Spain	Complejo Hospitalario Nuestra Señora de la Candelaria; Servicio de Oncologia	Santa Cruz de Tenerife	Tenerife
Spain	Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Hematologia	Santiago de Compostela	LA Coruña
Spain	Complejo Asistencial de Segovia	Segovia
Spain	Hospital Univ. Nuestra Señora de Valme; Servicio de Hematologia	Sevilla
Spain	Hospital Universitario Virgen Macarena; Servicio de Hematologia	Sevilla
Spain	Hospital Mutua de Terrassa; Servicio de Hematologia	Terrassa	Barcelona
Spain	Hospital de Rio Hortega; Servicio de Hematologia	Valladolid
Spain	Complejo Hospitalario Universitario de Vigo; Servicio de Hematologia	Vigo	Pontevedra
Spain	Hospital De Txagorritxu; Servicio de Hematologia	Vitoria	Alava

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Administration-Associated Reactions (AARs)	AARs were defined as all adverse events (AEs) occurring within 24 hours of rituximab SC administration and which were considered related to study drug. AARs included infusion/injection-related reactions (IIRRs), injection-site reactions, administration site conditions and all symptoms thereof. Grading was completed according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), version 4.0.	From start of treatment to end of treatment (up to 32 months)
Secondary	Percentage of Participants With At Least One Grade >/= 3 Adverse Events (AEs)	An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Pre-existing conditions which worsen during a study are also considered as adverse events. Grading was completed according to the CTCAE, version 4.0.	From start of recruitment (10 months period) up to end of treatment at 32 months (total period up to 42 months)
Secondary	Percentage of Participants With At Least One Grade >/= 3 Infusion/ Injection Related Reactions (IIRRs)	Grading of IIRRs was completed according to the CTCAE, version 4.0.	From start of treatment to end of treatment (up to 32 months)
Secondary	Percentage of Participants With At Least One Serious Adverse Event (SAE)	SAE was defined as any experience that suggested a significant hazard, contraindication, side effect, or precaution, and fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/ birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here.	From start of recruitment (10 months period) up to end of treatment at 32 months (total period up to 42 months)
Secondary	Event-Free Survival (EFS)	EFS was defined as the time from first dose of rituximab IV to first occurrence of progressive disease (PD) or relapse, according to the International Working Group (IWG) response criteria or initiation of a non-protocol-specified anti-lymphoma therapy or death, whichever occurs first. PD: >/= 50% increase lymph nodes and nodal mass size, any new lesion, enlarged liver/spleen, reappearance bone marrow abnormalities.	From time of first dose of rituximab IV before study enrollment up to end of study (up to approximately 62 months)
Secondary	Progression-Free Survival (PFS)	PFS was defined as the time from first dose of rituximab IV to the first occurrence of progressive disease (PD) or relapse, according to the International Working Group (IWG) response criteria or death from any cause. PD: >/= 50% increase lymph nodes and nodal mass size, any new lesion, enlarged liver/spleen, reappearance bone marrow abnormalities.	From time of first dose of rituximab IV before study enrollment up to end of study (up to approximately 62 months)
Secondary	Overall Survival (OS)	OS was defined as the time from first dose of rituximab IV to death from any cause.	From time of first dose of rituximab IV before study enrollment up to end of study (up to approximately 62 months)
Secondary	Disease-Free Survival (DFS)	DFS was assessed in participants achieving complete response (CR) including complete response unconfirmed (Cru) and was defined as the period from the date of the initial CR/CRu until the date of relapse or death from any cause. CR: 1) disappearance of all evidence/symptoms of disease, 2) lymph nodes and nodal masses normal size, 3) enlarged spleen must have regressed in size, 4) normal bone marrow; CRu: see 1) and 3) of CR plus > 75% decrease in residual lymph node mass, indeterminate bone marrow. Reported here is the truncated mean estimate based on Kaplan-Meier analysis.	From time of first dose of rituximab IV before study enrollment up to end of study (up to approximately 62 months)
Secondary	Treatment Response Rate	Treatment response rate was classified according to the International Working Group (IWG) response criteria: CR/Cru, partial response (PR), stable disease (SD) and PD. CR: 1) disappearance of all evidence/symptoms of disease, 2) lymph nodes and nodal masses normal size, 3) enlarged spleen must have regressed in size, 4) normal bone marrow; CRu: see 1) and 3) of CR plus > 75% decrease in residual lymph node mass, indeterminate bone marrow; PR: >/= 50% decrease lymph nodes and nodal mass size; decrease in liver/spleen size, no new sites; SD: less than a PR, but is not PD; PD: >/= 50% increase lymph nodes and nodal mass size, any new lesion, enlarged liver/spleen, reappearance bone marrow abnormalities.	4-6 weeks after the last dose of Induction (Up to approximately 8 months)