Phase 1
Completed N=64
A Study to Compare Subcutaneous Versus Intravenous MabThera (Rituximab) in Combination With Chemotherapy in Patients With Chronic Lymphocytic Leukemia
Lymphocytic Leukemia, Chronic
Source: ClinicalTrials.gov NCT01292603 ↗
Enrolled (actual)
64
Serious AEs
37.0%
Results posted
Dec 2015
Primary outcomePrimary: Part 1: Subcutaneous Rituximab Dose Resulting in Trough Concentration (Ctrough) Levels Non-Inferior to Intravenous Rituximab — 1600 mg
Summary
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 or Days 1-5 of every cycle. The anticipated time on study drug is 24 weeks.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1: Subcutaneous Rituximab Dose Resulting in Trough Concentration (Ctrough) Levels Non-Inferior to Intravenous Rituximab |
1600 | — |
| PRIMARY Part 2: Rituximab C Trough Levels at Cycle 5 |
61.50; 97.53 | — |
| SECONDARY Part 2: Observed Area Under the Serum Concentration-Curve (AUC) of Rituximab at Cycle 6 |
3630.43; 4088.78 | — |
| SECONDARY Part 2: Maximum Observed Concentration (Cmax) of Rituximab at Cycle 6 |
279.78; 202.16 | — |
| SECONDARY Part 2: Time to Cmax (Tmax) of Rituximab at Cycle 6 |
0.22; 3.14 | — |
| SECONDARY Part 2: Terminal Half-Life of Rituximab at Cycle 6 |
30.09; 30.71 | — |
| SECONDARY Part 1: Percentage of Participants and Nurses Recording a Preference For Either SC or IV Administration |
88.0; 100.0; 91.0; 13.0; 0.0; 9.0 | — |
| SECONDARY Part 2: Physician/Nurse Opinion on Time Savings With Rituximab SC Compared With Rituximab IV |
21.0; 21.0; 23.0; 29.0; 26.0; 23.0 | — |
| SECONDARY Part 2: Physician/Nurse Opinion on Convenience of Rituximab SC Compared With Rituximab IV |
81.0; 77.0; 7.0; 9.0; 9.0; 4.0 | — |
| SECONDARY Part 1: Percentage of Participants With Anti-Rituximab Antibodies |
0.0; 100.0; 5.0; 95.1 | — |
| SECONDARY Part 2: Percentage of Participants With Anti-Rituximab Antibodies |
0.0; 2.4; 100.0; 97.6; 15.0; 12.0 | — |
| SECONDARY Part 1: Total Cluster Differentiation19 Positive (CD19+) B-Cell Counts by Visit |
2; 3; 0; 84; 2; 1 | — |
| SECONDARY Part 1: Percentage of Participants With Total B-Cell Depletion by Visit |
93.3; 92.3; 100.0; 0.0; 100.0; 93.3 | — |
| SECONDARY Part 2: Total CD19+ B-Cell Counts by Visit |
68905; 50565; 338; 253; 163; 168 | — |
| SECONDARY Part 2: Percentage of Participants With Total B-Cell Depletion by Visit |
0.0; 0.0; 23.9; 31.1; 32.3; 37.9 | — |
Eligibility 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 unless clearly due to vaccination
- 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
Data sourced from ClinicalTrials.gov (NCT01292603). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.