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: Cyclophosphamide Drug: Fludarabine Drug: rituximab [MabThera]	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

Genetic and Rare Diseases Information Center resources: Chronic Lymphocytic Leukemia Leukemia, B-cell, Chronic

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 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 ]
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 ]


Enrollment:	240
Study Start Date:	April 2011
Estimated Study Completion Date:	November 2017
Estimated Primary Completion Date:	November 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1	Drug: Cyclophosphamide Days 1-3 of cycles 1-6 Drug: Fludarabine Days 1-3 of cycles 1-6 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.
Experimental: 2	Drug: Cyclophosphamide Days 1-3 of cycles 1-6 Drug: Fludarabine Days 1-3 of cycles 1-6 Drug: rituximab [MabThera] 6 cycles of intravenous MabThera
Experimental: 3	Drug: Cyclophosphamide Days 1-3 of cycles 1-6 Drug: Fludarabine Days 1-3 of cycles 1-6 Drug: rituximab [MabThera] One cycle of intravenous MabThera, followed by 5 cycles of subcutaneous MabThera

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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Show 83 Study Locations

Sponsors and Collaborators

Hoffmann-La Roche

Investigators


Study Director:	Clinical Trials	Hoffmann-La Roche

More Information

No publications provided by Hoffmann-La Roche

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Mao CP, Brovarney MR, Dabbagh K, Birnböck HF, Richter WF, Del Nagro CJ. Subcutaneous versus intravenous administration of rituximab: pharmacokinetics, CD20 target coverage and B-cell depletion in cynomolgus monkeys. PLoS One. 2013 Nov 12;8(11):e80533. doi: 10.1371/journal.pone.0080533. eCollection 2013.

Shpilberg O, Jackisch C. Subcutaneous administration of rituximab (MabThera) and trastuzumab (Herceptin) using hyaluronidase. Br J Cancer. 2013 Sep 17;109(6):1556-61. doi: 10.1038/bjc.2013.371. Epub 2013 Sep 3.


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:	February 5, 2015
Health Authority:	Spain: Agencia Espanola del Medicamento y Productos Sanitarios

Additional relevant MeSH terms:


Leukemia Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Immune System Diseases Immunoproliferative Disorders Leukemia, B-Cell Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Cyclophosphamide Fludarabine Fludarabine phosphate Rituximab	Alkylating Agents Antimetabolites Antimetabolites, Antineoplastic Antineoplastic Agents Antineoplastic Agents, Alkylating Antirheumatic Agents Immunologic Factors Immunosuppressive Agents Molecular Mechanisms of Pharmacological Action Myeloablative Agonists Pharmacologic Actions Physiological Effects of Drugs Therapeutic Uses

ClinicalTrials.gov processed this record on February 25, 2015