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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01292603
First received: February 8, 2011
Last updated: September 22, 2014
Last verified: September 2014
  Purpose

This randomized, parallel-group, multi-center study will compare the pharmacokin etics and safety of subcutaneous administration of MabThera (rituximab) versus i ntravenous MabThera in combination with chemotherapy in previously untreated pat ients 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 MabTher

a. In part 2, patients will be randomized to receive either 6 cycles of intraven ous MabThera, or 1 cycle of intravenous MabThera and 5 cycles of subcutaneous Ma bThera. Additionally, all patients will receive chemotherapy (fludarabine and cy clophosphamide) on days 1-3 of every cycle. The anticipated time on study drug i s 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:


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 ]

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):
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: September 22, 2014
Health Authority: Spain: Agencia Espanola del Medicamento y Productos Sanitarios

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

ClinicalTrials.gov processed this record on September 30, 2014