A Study to Compare Subcutaneous Versus Intravenous MabThera (Rituximab) in Combination With Chemotherapy in Patients With Chronic Lymphocytic Leukemia - Full Text View

Purpose

This randomized, parallel-group, multi-center study will compare the pharmacokinetics and safety of subcutaneous administration of MabThera (rituximab) versus intravenous MabThera in combination with chemotherapy in previously untreated patients with chronic lymphocytic leukemia (CLL). The study consists of 2 parts. In part 1, patients who have previously received 4 cycles of intravenous MabThera will receive in Cycle 5 intravenous MabThera and in Cycle 6 subcutaneous MabThera. In part 2, patients will be randomized to receive either 6 cycles of intravenous MabThera, or 1 cycle of intravenous MabThera and 5 cycles of subcutaneous MabThera. Additionally, all patients will receive chemotherapy (fludarabine and cyclophosphamide) on days 1-3 of every cycle. The anticipated time on study drug is 20 weeks.

Condition	Intervention	Phase
Lymphocytic Leukemia, Chronic	Drug: rituximab [MabThera] Drug: Fludarabine Drug: Cyclophosphamide	Phase 1

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	An Adaptive, Comparative, Randomized, Parallel-group, Multi Center, Phase Ib Study of Subcutaneous (SC) Rituximab Versus Intravenous (IV) Rituximab Both in Combination With Chemotherapy (Fludarabine and Cyclophosphamide), in Patients With Previously Untreated CLL

Resource links provided by NLM:

MedlinePlus related topics: Chronic Lymphocytic Leukemia Leukemia

Drug Information available for: Cyclophosphamide Fludarabine Fludarabine phosphate Rituximab

U.S. FDA Resources

Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:

Part 1: C(trough) levels of subcutaneous MabThera [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
Part 2: Non-inferiority in observed C(trough) levels between subcutaneous and intravenous MabThera [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Part 1: Injection-related reactions during the subcutaneous cycle [ Time Frame: Week 6 ] [ Designated as safety issue: No ]
Part 1: Patients and nurse preference regarding subcutaneous and intravenous administration [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
Part 2: Safety (nature and incidence of adverse events) [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Part 2: Physician and nurse opinion on time savings with subcutaneous MabThera [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Part 2: Physician and nurse opinion on the convenience of subcutaneous MabThera [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Part 1 and 2: Pharmacokinetics (Area under curve for subcutaneous and intravenous MabThera) [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Part 1 and 2: Immunogenicity of subcutaneous MabThera [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]
Part 1 and 2: Change of blood B-cell levels [ Time Frame: 20 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	200
Study Start Date:	April 2011
Estimated Study Completion Date:	July 2018
Estimated Primary Completion Date:	July 2018 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1	Drug: rituximab [MabThera] After 4 cycles of intravenous MabThera without experiencing grade 3 or 4 infusion-related reactions. patients will receive 1 additional cycle of intravenous MabThera and 1 cycle of subcutaneous MabThera. Drug: Fludarabine Days 1-3 of cycles 1-6 Drug: Cyclophosphamide Days 1-3 of cycles 1-6
Experimental: 2	Drug: rituximab [MabThera] 6 cycles of intravenous MabThera Drug: Fludarabine Days 1-3 of cycles 1-6 Drug: Cyclophosphamide Days 1-3 of cycles 1-6
Experimental: 3	Drug: rituximab [MabThera] One cycle of intravenous MabThera, followed by 5 cycles of subcutaneous MabThera Drug: Fludarabine Days 1-3 of cycles 1-6 Drug: Cyclophosphamide Days 1-3 of cycles 1-6

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Adult patients, >/=18 years of age
Patients with treatment-requiring chronic lymphocytic leukemia (CLL)
Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Life expectancy >6 months

Exclusion Criteria:

Transformation to aggressive B-cell malignancy
History of other malignancy unless the patient was treated with curative intent and has been in remission for more than 5 years prior to enrolment
HIV or Hepatitis B positive
Inadequate liver or renal function
Any coexisting medical or psychological condition that would preclude participation in the required study procedures

Additional exclusion criterion for Part 1:

Any previous treatment for CLL except for up to 4 cycles of rituximab iv in combination with FC chemotherapy as first-line treatment for CLL

Additional exclusion criterion for Part 2:

Any previous treatment for CLL

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01292603

Contacts

Contact: Please reference Study ID Number: BO25341 www.roche.com/about_roche/roche_worldwide.htm

888-662-6728 (U.S. Only)

genentechclinicaltrials@druginfo.com

Show 83 Study Locations

Sponsors and Collaborators

Hoffmann-La Roche

Investigators

Study Director:

Clinical Trials

Hoffmann-La Roche

More Information

No publications provided

Responsible Party:	Hoffmann-La Roche
ClinicalTrials.gov Identifier:	NCT01292603 History of Changes
Other Study ID Numbers:	BO25341, 2010-021380-32
Study First Received:	February 8, 2011
Last Updated:	May 7, 2013
Health Authority:	Spain: Agencia Espanola del Medicamento y Productos Sanitarios

Additional relevant MeSH terms:

Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Chronic Disease
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Disease Attributes
Pathologic Processes
Cyclophosphamide
Fludarabine monophosphate

Rituximab
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on May 16, 2013