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

Chronic Lymphocytic Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01848145
• Other study ID #: SCRI CLL 18
• Status: Active, not recruiting
• Phase: Phase 2
• First received: May 2, 2013
• Last updated: October 19, 2016
• Start date: July 2013
• Est. completion date: March 2017

Study information

• Verified date: October 2016
• Source: SCRI Development Innovations, LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 34
• Est. completion date: March 2017
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Lymphocytic Leukemia
• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid

Intervention

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.

Locations

Country	Name	City	State
United States	Chattanooga Oncology Hematology Associates	Chattanooga	Tennessee
United States	Oncology Hematology Associates	Cincinnati	Ohio
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	Florida Cancer Specialists-South	Fort Myers	Florida
United States	Tennessee Oncology PLLC	Nashville	Tennessee
United States	Florida Cancer Specialists-North	St. Petersburg	Florida

Sponsors (2)

Lead Sponsor	Collaborator
SCRI Development Innovations, LLC	GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The number of adverse events that occur with an accelerated infusion schedule of ofatumumab as a measure of safety and tolerability.	All adverse events (AEs) will be tabulated together and individually (per type of AE) to assess safety.	weekly for 8 weeks, then monthly for 4 months	Yes
Secondary	Peripheral blood sampling (50mL) and banking of cells to be measured and correlated with response to treatment and response duration with ofatumumab.	Correlation of infusion reactions with pre-treatment clinical characteristics and FcGamma polymorphisms. Other potential correlatives include CLL-related markers and immune function measurements.	At baseline	No