Phase 3
Completed N=54
Study to Assess the Effect of Treatment With Bendamustine in Combination With Rituximab on QT Interval in Patients With Advanced Indolent Non-Hodgkin's Lymphoma (NHL) or Mantle Cell Lymphoma (MCL)
Source: ClinicalTrials.gov NCT01073163 ↗Enrolled (actual)
54
Serious AEs
26.4%
Results posted
Apr 2014
Primary outcomePrimary: Mean Change From Baseline in QT Interval as Corrected by the Fridericia Method (QTcF) at End of Infusion — 410.4; 6.7 milliseconds (ms)
Summary
The primary objective of this study is to assess the effect of treatment with bendamustine on cardiac repolarization as reflected by the rate-corrected QT interval by the Fridericia method (QTcF).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Mean Change From Baseline in QT Interval as Corrected by the Fridericia Method (QTcF) at End of Infusion |
410.4; 6.7 | — |
| SECONDARY Mean Change From Baseline in QTcF at 1 Hour Postinfusion |
410.4; 4.1 | — |
| SECONDARY Number of Participants With QTcF New Outlier Events at End of Infusion and 1 Hour Postinfusion |
0; 0; 1; 0; 0; 0 | — |
| SECONDARY Number of Participants With New Onset ECG Waveform Morphological Changes |
— | — |
| SECONDARY Number of Participants With Treatment-Emergent Cardiac Disorders |
3; 2; 1; 1; 1; 0 | — |
| SECONDARY Change From Baseline in QTcF at Maximum Concentration (Cmax) of Bendamustine and Its Metabolites (M3 and M4) |
5.4097; 5.9995; 7.1390 | — |
| SECONDARY Model-predicted Bayesian Bendamustine Clearance in the Presence of Rituximab |
32.9 | — |
| SECONDARY Rituximab Concentrations at 0.5 Hours, 24 Hours, and 7 Days Postinfusion |
173.0; 105.0; 30.5 | — |
| SECONDARY Percentage of Participants With Complete Response (CR) |
40; 55; 43 | — |
| SECONDARY Percentage of Participants With Overall Response |
93; 100; 94 | — |
| SECONDARY Overview of Adverse Events |
53; 33; 52; 1; 14; 1 | — |
| SECONDARY Eastern Cooperative Oncology Group (ECOG) Performance Status at Endpoint |
10; 35; 8 | — |
| SECONDARY Worst Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grades for Hematology Laboratory Tests Results Overall |
5; 12; 11; 12; 40; 36 | — |
Eligibility Criteria
Key Inclusion Criteria
- Histopathologic confirmation of one of the following CD20+ B-cell non-Hodgkin's lymphomas. Tissue diagnostic procedures must be performed within 6 months of study entry and with biopsy material available for review:
- follicular lymphoma (grade 1 or 2)
- immunoplasmacytoma/immunocytoma (Waldenstrom's macroglobulinemia)
- splenic marginal zone B-cell lymphoma
- extra-nodal marginal zone lymphoma of mucosa associated lymphoid tumor (MALT) type
- nodal marginal zone B-cell lymphoma
- mantle cell lymphoma
- Meets one of the following need-for-treatment criteria (with the exception of mantle cell lymphoma for which treatment is indicated):
- presence of at least one of the following B-symptoms:
- fever (>38ºC) of unclear etiology
- night sweats
- weight loss of greater than 10% within the prior 6 months
- large tumor mass (bulky disease)
- presence of lymphoma-related complications, including narrowing of ureters or bile ducts, tumor-related compression of a vital organ, lymphoma induced pain, cytopenias related to lymphoma/leukemia, splenomegaly, pleural effusions, or ascites
- hyperviscosity syndrome due to monoclonal gammopathy
- CD20-positive B cells in lymph node biopsy or other lymphoma pathology specimen
- No prior treatment. Patients on "watch and wait" may enter the study if a recent biopsy (obtained within the last 6 months) is available.
- Adequate hematologic function (unless abnormalities related to lymphoma infiltration of the bone marrow or hypersplenism due to lymphoma) as follows:
- hemoglobin of >= 10.0 g/dL
- absolute neutrophil count (ANC) >=1.5*10^9/L
- platelet count >=100*10^9/L
- Bidimensionally measurable disease (field not previously radiated)
- Able to provide written informed consent
- Eastern Cooperative Oncology Group (ECOG) performance status =6 months
- Serum creatinine of =50 mL/min
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5* upper limit of normal (ULN), and alkaline phosphatase and total bilirubin within normal limits
- Left ventricular ejection fraction (LVEF) >=50% by multiple gated acquisition scan (MUGA) or cardiac echocardiogram (ECHO), prior for any patient to be treated with rituximab/cyclophosphamide/doxorubicin/vincristine/prednisolone (R-CHOP)
- A medically accepted method of contraception to be used by women of childbearing potential (not surgically sterile or at least 12 months naturally postmenopausal)
- Men capable of producing offspring and not surgically sterile must practice abstinence or use a barrier method of birth control
Key Exclusion Criteria
- Chronic lymphocytic leukemia, small lymphocytic lymphoma (SLL), or grade 3 follicular lymphoma
- Transformed disease. Bone marrow blasts are permitted, however, transformed disease indicating leukemic involvement is not permitted
- Central nervous system (CNS) lymphomatous involvement or leptomeningeal lymphoma
- Prior radiation for non-Hodgkin's lymphoma (NHL), except for a single course of locally delimited radiation therapy with a radiation field not exceeding 2 adjacent lymph node regions
- Active malignancy, other than NHL, within the past 3 years except for localized prostate cancer treated with hormone therapy, cervical carcinoma in situ, breast cancer in situ, or non-melanoma skin cancer following definitive treatment
- New York Heart Association (NYHA) Class III or IV heart failure, arrhythmias or unstable angina, electrocardiographic evidence of active ischemia or active conduction system abnormalities, or myocardial infarction within the last 6 months. (Prior to study entry, ECG abnormalities at screening must be documented by the investigator as not medically relevant)
- Known human immunodeficiency virus (HIV) positivity
- Active hepatitis B or hepatitis C infection (Hepatitis B surface antigen testing required)
- Women who are pregnant or lactating
- Corticosteroids for treatment of lymphoma within 28 days of study entry. Chronically administered low-dos
Data sourced from ClinicalTrials.gov (NCT01073163). 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.