Drug-drug Interaction Study of Ofatumumab With Bendamustine in Subjects With Indolent B-cell Non-Hodgkin's Lymphoma

NCT01691807 | Completed Phase 1

• 1 other identifier: 113603
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to evaluate the potential drug-drug interactions between ofatumumab and bendamustine in subjects with previously untreated or relapsed indolent B-cell non-Hodgkin's lymphoma (NHL).

Conditions

Cancer

Keywords

Non-Hodgkin's Lymphoma; drug-drug interaction; ofatumumab; bendamustine

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetic measures of Cmax and Area Under the Curve by analysis of blood samples for the amount of each drug present at different timepoints.

  The amount of ofatumumab and bendamustine in the blood will be measured when given individually or together to obtain Cmax and Area Under the Curve. Bendamustine levels will be collected at Cycles 1 and 2: Predose, 0.25, 0.5, 0.75, 1 (end of infusion), 1.25, 1.5, 2, 3, 4, 6, 8, 10, 12, 14, and 24 hours. Ofatumumab will be collected at Cycle 4: Predose, end of infusion, then 1, 2, 24, and 72 hours after end of infusion, then once each on Days 8, 15, and 22.

  4 months

Secondary Outcomes (2)

• Changes in vital signs and the number adverse events

  14 months

• Measure the extent of the disease by CT scan or flow cytometry analysis

  14 months

Study Arms (2)

Arm A

EXPERIMENTAL

bendamustine and ofatumumab treatment of NHL

Drug: ofatumumab; Drug: bendamustine

Arm B

EXPERIMENTAL

ofatumumab only treatment of NHL

Drug: ofatumumab

Interventions

ofatumumab DRUG

treatment for NHL

Arm A; Arm B

bendamustine DRUG

treatment for NHL

Arm A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects with previously untreated or relapsed indolent B-cell NHL requiring treatment. Indolent NHL is defined as small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL), and follicular lymphoma (FL); grades 1, 2, and 3A, defined according to WHO guidelines. Tumor verified to be CD20+ positive from a previous or current lymph node biopsy.
• At least 4 weeks after previous anti-cancer chemotherapy, or radiotherapy treatment.
• At least 12 weeks after previous anti-CD20 radioimmunotherapy, anti-CD20 antibody treatment, and non-anti-CD20 monoclonal antibody treatment.
• Subjects who give consent to this study participation and sign the informed consent form.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
• Age greater than or equal to 18 years at informed consent.
• A female subject is eligible to participate if she is of Non-childbearing potential or required to use a contraception method.
• Male subjects with female partners of child-bearing potential must agree to use a contraception method.
• Subjects must agree to use contraception until 12 months after the last dose of study drug.

You may not qualify if:

• Subjects who failed to achieve a complete remission (CR) or partial remission (PR) or progressed within 6 months of last rituximab-containing therapy
• Previous treatment with ofatumumab.
• Prior bendamustine treatment not resulting in a complete remission and partial remission for at least 6 months.
• Previous allogeneic stem cell transplant.
• Previous autologous stem cell transplant.
• High dose steroids greater than or equal to 100 mg prednisone/day (or equivalent) for greater than or equal to 7 consecutive days, given as concomitant medication, within 3 months prior to randomization. No more than 20 mg prednisone or equivalent daily at the time of randomization.
• Grade 3b follicular lymphoma or evidence that the indolent lymphoma has transformed to aggressive lymphoma as verified by biopsy confirmation.
• Known central nervous system involvement by NHL.
• Other past or current malignancy. Subjects who have been free of malignancy for at least 2 years, or have a history of definitively treated non-melanoma skin cancer, or successfully treated in situ carcinoma, are eligible.
• Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, and active Hepatitis B or C. Prophylactic antibiotics to prevent recurrent of a prior infection (such as shingles, sinusitis or upper respiratory infection) is allowed.
• Clinically significant cardiac disease as judged by the investigator, including unstable angina, acute myocardial infarction within 6 months of randomization, and uncontrolled congestive heart failure (CHF) or arrhythmia. Patients with a history of CHF or arrhythmia are eligible if their cardiac disease is well controlled on a stable medical regimen.
• History of significant cerebrovascular disease or event with significant symptoms or sequelae (as judged by the investigator).
• Significant concurrent, uncontrolled medical condition that in the opinion of the investigator contraindicates participation this study.
• Positive serology for Hepatitis B (HB) defined as a positive test for Hepatitis B surface antigen (HBsAg). In addition, if negative for HBsAg but Hepatitis B core antibody (HBcAb) positive (regardless of Hepatitis B surface antibody \[HBsAb\] status), a HB DNA test will be performed and if positive the subject will be excluded. If HBV DNA is negative, the subject may be included but must undergo Hepatitis B virus (HBV) DNA monitoring (see Section 7.7.5). Prophylactic antiviral therapy may be initiated at the discretion of the investigator.
• Current active liver or biliary disease (subjects with Gilbert's syndrome or asymptomatic gallstones, liver metastases related to indolent NHL or otherwise stable chronic liver disease per investigator assessment, are eligible).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (5)

Novartis Investigative Site

Birmingham, Alabama, 35294-3300, United States

Location

Novartis Investigative Site

Southaven, Mississippi, 38671, United States

Location

Novartis Investigative Site

Houston, Texas, 77030, United States

Location

Novartis Investigative Site

San Antonio, Texas, 78229, United States

Location

Novartis Investigative Site

Morgantown, West Virginia, 26506, United States

Location

MeSH Terms

Conditions

Neoplasms; Lymphoma, Non-Hodgkin

Interventions

ofatumumab; Bendamustine Hydrochloride

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2012
• First Posted: September 25, 2012
• Study Start: January 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: February 28, 2018

Record last verified: 2018-02

Locations

US (5)