Rapid Infusion of Ofatumumab in Patients With Previously Treated Chronic Lymphocytic Leukemia

NCT01848145 | Completed Phase 2 Results

• 1 other identifier: SCRI CLL 18
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 6

Brief Summary

This is a Phase II, single-arm study of ofatumumab investigating the safety of an accelerated infusion schedule of ofatumumab in patients who have received at least one prior therapy for CLL. The primary endpoint is to evaluate the number of subjects able to complete infusion number 3 (2000 mg) within 15 minutes of the planned time.

Conditions

Chronic Lymphocytic Leukemia

Keywords

Chronic Lymphocytic Leukemia; Ofatumumab; Rapid Infusion

Outcome Measures

Primary Outcomes (1)

• Percent of Patients Who Complete an Accelerated Infusion Regimen Within 15 Minutes of the Planned 2-hour Treatment.

  Defined as percent of patients who are able to complete the Day 8 (2000 mg IV Ofatumumab) infusion within 15 minutes of the planned 2-hour treatment goal.

  At Week 2, Day 1 of therapy

Secondary Outcomes (5)

• Duration of Time to Complete Individual Infusions of an Accelerated Infusion Schedule of Ofatumumab

  Week 1 - Days 1 and 3, and Week 2, Day 1

• Overall Response Rate (ORR)

  At weeks 12 and 28

• Progression Free Survival

  For 28 weeks during therapy then every 3 months for 2 years and every 6 months thereafter.

• Overall Survival

  For 28 weeks during therapy then every 3 months for 2 years and every 6 months thereafter.

• Number of Patients With Infusion-related Reactions Assessed According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v. 4.0.

  up to 28 weeks

Study Arms (1)

Ofatumumab

EXPERIMENTAL

Rapid Infusion of Ofatumumab

Drug: Ofatumumab

Interventions

Ofatumumab DRUG

The first dose of ofatumumab administered on Day 1 will be 300 mg to minimize infusion reactions. If the initial 300 mg dose of ofatumumab is well-tolerated, without occurrence of any infusion-associated AEs of \>= grade 3, on Day 3 ofatumumab will increase to 1000 mg IV. If the Day 3 dose was well-tolerated (i.e., no infusion-associated AE \>= grade 3), on Day 8 the ofatumumab dose will escalate to 2000 mg IV. To achieve the primary endpoint for this study, 20% of the 2000 mg ofatumumab dose only will be administered over the first 30 minutes and if tolerated the remaining 80% of the dose will be infused over the remaining 1.5/hours of each treatment. Ofatumumab doses, weeks 3-8, will remain at 2000 mg IV with no further dose escalations. If the Day 8 (Week 2) dose is tolerated all subsequent doses may be infused in the same manner.

Also known as: Arzerra

Ofatumumab

Eligibility Criteria

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

You may qualify if:

• CD20+ B-cell chronic lymphocytic leukemia (B-CLL) according to International Workshop on CLL Working Group (IWCLL WG) Diagnostic Criteria.
• Have received at least one prior therapy for CLL.
• If previously treated with ofatumumab must have achieved at least a partial response (PR) and maintained PR for \>= 6 months.
• Requires treatment according to IWCLL-Working Group guidelines.
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) \<=1.
• Laboratory parameters \<=7 days prior to treatment initiation:
• Creatinine \<= 1.5 mg/dL upper limit normal (ULN)
• Aspartate amino transferase (AST) or alanine amino transferase (ALT) \<= 3.0 x ULN
• Alkaline phosphatase (ALP) \<= 3.0 x ULN
• Total Bilirubin level of \< 1.5 mg/dL x the institutional ULN unless secondary to Gilbert's disease (or pattern consistent with Gilbert's)
• Hepatitis B sAg negative and HepB cAb negative. Note: Patients who are HepB sAg negative but are HepB cAb positive (regardless of HepB sAb status) will NOT be allowed.
• Women of childbearing potential must have a negative serum pregnancy test performed \<=72 hours prior to start of treatment. Women of childbearing potential or men with partners of childbearing potential must use effective birth control measures during treatment. If a woman becomes pregnant or suspects she is pregnant while participating in this study, she must agree to inform her treating physician immediately.
• Accessible for treatment and follow-up.
• Able to understand the nature of this study, give written informed consent prior to study entry, and comply with study requirements.
• No prior antibody therapy for CLL within the previous 3 months.

You may not qualify if:

• Previous treatment with ofatumumab that resulted in a Grade 3 or 4 infusion reaction.
• Treatment for CLL within last 4 weeks. (Patients who have received steroids or IVIG for autoimmune complications of CLL are eligible).
• Current active hepatic or biliary disease (with the exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease, per assessment by the treating physician).
• Active bacterial or viral infection or infection requiring intravenous antibiotic treatment at the time of accrual.
• Central nervous system lymphoma/CLL.
• Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (i.e., Richter's transformation).
• History of other malignancy \<= 2 years of study entry which could affect compliance with the protocol or interpretation of results. History of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix, low grade, early-stage, localized prostate cancer treated surgically with curative intent, ductal carcinoma in situ (DCIS) of the breast treated with curative intent, are generally eligible.
• Active hepatitis B or C or known HIV positive.
• Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to visit 1, whichever is longer.
• History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae.
• Clinically significant cardiac disease including unstable angina, acute myocardial infarction (within 6 months of enrollment), congestive heart failure (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities.
• Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease which in the opinion of the investigator may represent a risk for the patient.

Sponsors & Collaborators

• SCRI Development Innovations, LLC: lead
• GlaxoSmithKline: collaborator
• Novartis: collaborator

Study Sites (6)

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

Location

Florida Cancer Specialists-South

Fort Myers, Florida, 33916, United States

Location

Florida Cancer Specialists-North

St. Petersburg, Florida, 33705, United States

Location

Oncology Hematology Associates

Cincinnati, Ohio, 45242, United States

Location

Chattanooga Oncology Hematology Associates

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology PLLC

Nashville, Tennessee, 37203, United States

Location

Related Publications (1)

• Donnellan W, Berdeja JG, Shipley D, Arrowsmith ER, Wright D, Lunin S, Brown R, Essell JH, Flinn IW. A Phase II Trial Evaluating the Safety of Rapid Infusion of Ofatumumab in Patients with Previously Treated Chronic Lymphocytic Leukemia. Oncologist. 2017 Oct;22(10):1156-e111. doi: 10.1634/theoncologist.2017-0236. Epub 2017 Jul 7.

  PMID: 28687625 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Interventions

ofatumumab

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Charles Davis, RAC
• Organization: SCRI Development Innovations

Charles.Davis2@scri-innovations.com

615-524-4341

Study Officials

• Ian Flinn, MD, PhD

  SCRI Development Innovations, LLC

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2013
• First Posted: May 7, 2013
• Study Start: July 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: March 1, 2017
• Last Updated: June 6, 2017
• Results First Posted: June 6, 2017

Record last verified: 2017-05

Locations

US (6)