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

December 4, 2018 updated by: Hoffmann-La Roche

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.

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

140

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Spain
      • Almeria, Spain, 04009
        • Complejo Hospitalario Torrecardenas; Servicio de Hematologia
      • Burgos, Spain, 09006
        • Hospital Universitario de Burgos, Servicio de Hematología
      • Castellon, Spain, 12004
        • Hospital General de Castellon; Servicio de Hematologia
      • Cordoba, Spain, 14004
        • Hospital Universitario Reina Sofia; Servicio de Hematologia
      • Granada, Spain, 18014
        • Hospital Universitario Virgen de las Nieves; Servicio de Hematologia
      • Guadalajara, Spain, 19002
        • Hospital Universitario de Gaudalajara; Hematología
      • Lerida, Spain, 25198
        • Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Hematologia
      • Madrid, Spain, 28031
        • Hospital Infanta Leonor; Servicio de Hematologia
      • Madrid, Spain, 28040
        • Fundacion Jimenez Diaz; Servicio de Hematologia
      • Madrid, Spain, 28040
        • Hospital Universitario Clínico San Carlos; Servicio de Hematología
      • Madrid, Spain, 28050
        • HOSPITAL DE MADRID NORTE SANCHINARRO- CENTRO INTEGRAL ONCOLOGICO CLARA CAMPAL; Servicio Hematologia
      • Madrid, Spain, 28222
        • Hospital Universitario Puerta de Hierro; Servicio de Hematologia
      • Madrid, Spain, 28805
        • Hospital Universitario Principe de Asturias; Servicio de Hematología
      • Malaga, Spain, 29010
        • Hospital Univ. Virgen de la Victoria
      • Murcia, Spain, 30008
        • Hospital General Universitario J.M Morales Meseguer; Servicio de Hematología
      • Murcia, Spain, 30120
        • Hospital Universitario Virgen de Arrixaca; Servicio de Hematologia
      • Pontevedra, Spain, 36071
        • Complejo Hospitalario de Pontevedra; Servicio de Hematologia
      • Segovia, Spain, 40002
        • Complejo Asistencial de Segovia
      • Sevilla, Spain, 41009
        • Hospital Universitario Virgen Macarena; Servicio de Hematologia
      • Sevilla, Spain, 41014
        • Hospital Univ. Nuestra Señora de Valme; Servicio de Hematologia
      • Valladolid, Spain, 47010
        • Hospital de Rio Hortega; Servicio de Hematologia
    • Alava
      • Vitoria, Alava, Spain, 01009
        • Hospital De Txagorritxu; Servicio de Hematologia
    • Alicante
      • Elda, Alicante, Spain, 03600
        • Hospital General de Elda; Servicio de Hematologia
    • Barcelona
      • Granollers, Barcelona, Spain, 08400
        • Hospital de Granollers, Servicio de Hematología
      • Terrassa, Barcelona, Spain, 08221
        • Hospital Mutua de Terrassa; Servicio de Hematologia
    • Islas Baleares
      • Palma de Mallorca, Islas Baleares, Spain, 07198
        • Hospital Son Llatzer; Servicio de Hematologia
    • LA Coruña
      • La Coruna, LA Coruña, Spain, 15006
        • Complejo Hospitalario Universitario A Coruña (CHUAC); Servicio de Hematologia
      • Santiago de Compostela, LA Coruña, Spain, 15706
        • Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Hematologia
    • LA Rioja
      • Logroño, LA Rioja, Spain, 26006
        • Complejo Hospitalario San Millan - San Pedro; Servicio Hematologia
    • Leon
      • León, Leon, Spain, 24008
        • Complejo Asistencial de León, Servicio de Hematología
    • Madrid
      • Fuenlabrada, Madrid, Spain, 28943
        • Hospital Universitario de Fuenlabrada; Servicio de Hematologia
      • Leganes, Madrid, Spain, 28911
        • Hospital Severo Ochoa; Servicio de Hematologia
      • Mostoles, Madrid, Spain, 28935
        • Hosital Universitario de Mostoles;Servicio de Hematologia
    • Navarra
      • Pamplona, Navarra, Spain, 31008
        • Clinica Universitaria de Navarra; Servicio de Hematologia
      • Pamplona, Navarra, Spain, 31008
        • Hospital de Navarra, Servicio de Hematología
    • Pontevedra
      • Vigo, Pontevedra, Spain, 36204
        • Complejo Hospitalario Universitario de Vigo; Servicio de Hematologia
    • Tenerife
      • Santa Cruz de Tenerife, Tenerife, Spain, 38010
        • Complejo Hospitalario Nuestra Señora de la Candelaria; Servicio de Oncologia
    • Vizcaya
      • Bilbao, Vizcaya, Spain, 48013
        • Hospital de Basurto; Servicio de Hematologia
      • Galdakao, Vizcaya, Spain, 48960
        • Hospital de Galdakano; Servicio de Hematologia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Subcutaneous Rituximab
Participants with CD20+ non-Hodgkin's follicular lymphoma (FL) or diffuse large B-cell lymphoma (DLBCL), who had already received at least one full dose of intravenous (IV) rituximab will be treated with subcutaneous (SC) rituximab. Participants with FL will be administered 1400 mg rituximab during induction therapy (once monthly for 4-7 cycles) and maintenance therapy (once every 2 months for 6-12 cycles). Participants with DLBCL will be administered 1400 mg SC of rituximab 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.
Drug: Rituximab
1400 mg will be injected subcutaneously (SC).
Other Names:
  • Rituxan
  • MabThera

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Administration-Associated Reactions (AARs)
Time Frame: From start of treatment to end of treatment (up to 32 months)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants With At Least One Grade >/= 3 Adverse Events (AEs)
Time Frame: From start of recruitment (10 months period) up to end of treatment at 32 months (total period up to 42 months)
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)
Percentage of Participants With At Least One Grade >/= 3 Infusion/ Injection Related Reactions (IIRRs)
Time Frame: From start of treatment to end of treatment (up to 32 months)
Grading of IIRRs was completed according to the CTCAE, version 4.0.
From start of treatment to end of treatment (up to 32 months)
Percentage of Participants With At Least One Serious Adverse Event (SAE)
Time Frame: From start of recruitment (10 months period) up to end of treatment at 32 months (total period up to 42 months)
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)
Event-Free Survival (EFS)
Time Frame: From time of first dose of rituximab IV before study enrollment up to end of study (up to approximately 62 months)
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)
Progression-Free Survival (PFS)
Time Frame: From time of first dose of rituximab IV before study enrollment up to end of study (up to approximately 62 months)
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)
Overall Survival (OS)
Time Frame: From time of first dose of rituximab IV before study enrollment up to end of study (up to approximately 62 months)
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)
Disease-Free Survival (DFS)
Time Frame: From time of first dose of rituximab IV before study enrollment up to end of study (up to approximately 62 months)
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)
Treatment Response Rate
Time Frame: 4-6 weeks after the last dose of Induction (Up to approximately 8 months)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hoffmann-La Roche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 11, 2013

Primary Completion (Actual)

April 11, 2017

Study Completion (Actual)

April 11, 2017

Study Registration Dates

First Submitted

November 8, 2013

First Submitted That Met QC Criteria

November 13, 2013

First Posted (Estimate)

November 19, 2013

Study Record Updates

Last Update Posted (Actual)

December 26, 2018

Last Update Submitted That Met QC Criteria

December 4, 2018

Last Verified

December 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ML28943
  • 2013-001118-14 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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