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

Rapid Infusion of Ofatumumab in Patients With Previously Treated Chronic Lymphocytic Leukemia, a Phase II Trial

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.

Study Overview

• Status: Completed
• Conditions: Chronic Lymphocytic Leukemia
• Intervention / Treatment: Drug: Ofatumumab

Detailed Description

The purpose of this study is to develop an accelerated infusion regimen that allows ofatumumab to be delivered in a safe manner while minimizing the time required administering the treatment. We hypothesize there will be fewer infusion-related reactions using the proposed dose-dense approach the first week before accelerating the rate of infusion.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Florida
    • Fort Myers, Florida, United States, 33916
      • Florida Cancer Specialists-South
    • Saint Petersburg, Florida, United States, 33705
      • Florida Cancer Specialists-North
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Associates
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Chattanooga Oncology Hematology Associates
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology PLLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. CD20+ B-cell chronic lymphocytic leukemia (B-CLL) according to International Workshop on CLL Working Group (IWCLL WG) Diagnostic Criteria.

2. 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.

3. Requires treatment according to IWCLL-Working Group guidelines.
4. Eastern Cooperative Oncology Group Performance Status (ECOG PS) <=1.

5. Laboratory parameters <=7 days prior to treatment initiation:

   1. Creatinine <= 1.5 mg/dL upper limit normal (ULN)
   2. Aspartate amino transferase (AST) or alanine amino transferase (ALT) <= 3.0 x ULN
   3. Alkaline phosphatase (ALP) <= 3.0 x ULN
   4. Total Bilirubin level of < 1.5 mg/dL x the institutional ULN unless secondary to Gilbert's disease (or pattern consistent with Gilbert's)
6. 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.
7. 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.
8. Accessible for treatment and follow-up.
9. Able to understand the nature of this study, give written informed consent prior to study entry, and comply with study requirements.
10. No prior antibody therapy for CLL within the previous 3 months.

Exclusion Criteria:

1. Previous treatment with ofatumumab that resulted in a Grade 3 or 4 infusion reaction.
2. Treatment for CLL within last 4 weeks. (Patients who have received steroids or IVIG for autoimmune complications of CLL are eligible).
3. 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).
4. Active bacterial or viral infection or infection requiring intravenous antibiotic treatment at the time of accrual.
5. Central nervous system lymphoma/CLL.
6. Transformation of CLL to aggressive non-Hodgkin lymphoma (NHL) (i.e., Richter's transformation).
7. 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.
8. Active hepatitis B or C or known HIV positive.
9. 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.
10. History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae.
11. 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.
12. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Ofatumumab; Rapid Infusion of Ofatumumab

Drug: Ofatumumab; 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.; Other Names: Arzerra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Time to Complete Individual Infusions of an Accelerated Infusion Schedule of Ofatumumab	Defined as the actual mean infusion times, in minutes, for patients to complete a schedule of 3 infusions with the goal of completing Infusion #3 within 15 minutes of the planned 2-hour treatment time.	Week 1 - Days 1 and 3, and Week 2, Day 1
Overall Response Rate (ORR)	Defined as the percent of patients having a complete or partial response (CR or PR) assessed by International Workshop on CLL Working Group (IWCLLWG) Diagnostic Criteria (Hallek et al., 2008). CR = (a) Peripheral blood lymphocytes below 4000/µl; (b) Absence of significant lymphadenopathy by physical exam or radiographic scans (c) No hepatomegaly or splenomegaly; (d) Absence of constitutional symptoms; and blood counts above specified values. PR = (a) Decreased blood lymphocytes by 50% or more from the value prior to therapy;(b) No increase in any lymph node, and no new enlarged lymph node. Progressive Disease (PD) = An increase in 50% or more in greatest determined diameter of any previous site. Stable Disease (SD) = No evidence of CR or PR and no evidence of progressive disease.	At weeks 12 and 28
Progression Free Survival	Defined as the time from first treatment until objective tumor progression or death from any cause.	For 28 weeks during therapy then every 3 months for 2 years and every 6 months thereafter.
Overall Survival	Defined as the time from first treatment until death from any cause.	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.	Patients who received at least 1 dose of protocol treatment either Infusion #1 (300 mg), Infusion #2 (1000 mg) or Infusion #3 (2000 mg) are included in the assessment.	up to 28 weeks

Collaborators and Investigators

• Sponsor: SCRI Development Innovations, LLC
• Collaborators: GlaxoSmithKline; Novartis
• Investigators: Study Chair: Ian Flinn, MD, PhD, SCRI Development Innovations, LLC

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): March 1, 2017

Study Registration Dates

• First Submitted: May 2, 2013
• First Submitted That Met QC Criteria: May 6, 2013
• First Posted (Estimate): May 7, 2013

Study Record Updates

• Last Update Posted (Actual): June 6, 2017
• Last Update Submitted That Met QC Criteria: May 3, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Ofatumumab; Chronic Lymphocytic Leukemia; Rapid Infusion
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid; Antineoplastic Agents; Ofatumumab
• Other Study ID Numbers: SCRI CLL 18