Ofatumumab for Initial Systemic Treatment of Indolent B-cell Lymphoma

• ClinicalTrials.gov Identifier: NCT01239394
• Recruitment Status: Completed
• First Posted: November 11, 2010
• Results First Posted: March 17, 2017
• Last Update Posted: October 18, 2017
• Sponsor: Massachusetts General Hospital
• Collaborators: Dana-Farber Cancer Institute; Beth Israel Deaconess Medical Center; GlaxoSmithKline
• Information provided by (Responsible Party): Jeremy Abramson, MD, Massachusetts General Hospital

Tracking Information

• First Submitted Date: November 10, 2010
• First Posted Date: November 11, 2010
• Results First Submitted Date: January 25, 2017
• Results First Posted Date: March 17, 2017
• Last Update Posted Date: October 18, 2017
• Actual Study Start Date: December 2010
• Actual Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 17, 2017)

Efficacy: Complete Response Rate (CRR) [ Time Frame: 1-month post-treatment ]

Evaluate clinical efficacy of ofatumumab in previously untreated indolent B-cell lymphomas, as measured by complete response rate (CRR). Complete response = all previously enlarged fluorodeoxyglucose (FDG)-avid or positron emission tomography (PET)-positive lymph nodes regressed to normal size (<=1.5 cm in greatest diameter)

Original Primary Outcome Measures (submitted: November 10, 2010)

Efficacy [ Time Frame: 2 years ]

Evaluate clinical efficacy of ofatumumab in previously untreated indolent B-cell lymphomas, as measured by complete response rate.

Current Secondary Outcome Measures (submitted: March 17, 2017)

• Overall Response Rate (ORR) [ Time Frame: 1-month post-treatment ]
  Evaluate clinical efficacy of ofatumumab in previously untreated indolent B-cell lymphomas, as measured by overall response rate (ORR). Overall response = Complete response (CR) + Partial response (PR) CR = all previously enlarged fluorodeoxyglucose (FDG)-avid or positron emission tomography (PET)-positive lymph nodes regressed to normal size (<=1.5cm in greatest diameter) PR = >=50% decrease in SPD of up to six largest dominant masses, no increase in size of other nodes; FDG avid or PET positive before therapy, one or more nodes PET positive at previously involved site, or variably FDG avid or PET negative with regression at CT
• Progression-free Survival (PFS) [ Time Frame: 12 months ]
  Percentage of patients with progression-free survival during 12 months post-treatment progression-free survival: patients live with the disease, but it does not get worse
• Toxicity: Infusion Reactions, Grade 3-4 Infections, and Neutropenia [ Time Frame: 2 years ]
  Evaluate safety of ofatumumab monotherapy in this patient population Toxicities are graded 1 (mild), 2 (moderate), 3 (severe), and 4 (life-threatening)

Original Secondary Outcome Measures (submitted: November 10, 2010)

• Safety [ Time Frame: 2 years ]
  Evaluate safety of ofatumumab monotherapy in this patient population
• Pharmacodynamics [ Time Frame: 2 years ]
  Evaluate pharmacodynamics of B cell depletion
• Neutropenia [ Time Frame: 2 years ]
  Evaluate the incidence and duration of neutropenia
• Hypogammaglobulinemia [ Time Frame: 2 years ]
  Estimate incidence, severity and duration of hypogammaglobulinemia

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Ofatumumab for Initial Systemic Treatment of Indolent B-cell Lymphoma
• Official Title: Phase II Trial Ofatumumab for Initial Systemic Treatment of Indolent B-cell Lymphoma
• Brief Summary: Ofatumumab is a drug that works by attaching to the CD20 molecule found on the surface of cancerous B cells, and then triggering the death of those cells. It is approved by the FDA for treatment of another B-cell cancer, chronic lymphocytic leukemia, and also has evidence of success in people who's B-cell lymphomas have relapsed after initial treatments. In this research study we are looking to see if ofatumumab is effective and safe in treating previously untreated B-cell NHL.

Detailed Description

• Participants will receive ofatumumab once a week for 8 weeks by intravenous infusion (Days 1, 8, 15, 22, 29, 36, 43, and 50).
• Participants will be seen weekly during the 8 week treatment period and will have the following tests and procedures performed: Blood tests, performance status and physical examination.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Follicular Lymphoma
• Marginal Zone Lymphoma
• Small Lymphocytic Lymphoma

Intervention

Drug: ofatumumab

Weekly infusion for 8 weeks

Other Names:

• GSK1841157
• HuMax-CD20

Study Arms

ofatumumab

single-arm, open-label, interventional

Intervention: Drug: ofatumumab

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 26, 2017): 43
• Original Estimated Enrollment (submitted: November 10, 2010): 42
• Actual Study Completion Date: March 2015
• Actual Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Histologically confirmed indolent CD20+B-cell NHL of the following histologies: follicular lymphoma, grades 1-2; Marginal zone lymphoma (extranodal, nodal or splenic); small lymphocytic lymphoma; low-grade B-cell lymphoma not otherwise specified with CD20+ expression
• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension as 20mm or greater CT scan or MRI
• No previous chemotherapy, antibody therapy or radioimmunotherapy for this disease. Patients previously treated with external beam radiation alone are eligible
• 18 years of age or older
• Life expectancy of greater than 3 months
• ECOG Performance status of 0, 1 or 2
• Organ function as described in the protocol
• Women of child-bearing potential and men must agree so use adequate contraception prior to study entry and for the duration of study participation

Exclusion Criteria:

• Prior chemotherapy, antibody therapy or radioimmunotherapy for lymphoma
• Participants may not be receiving any other investigational agent
• Participants with known brain metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ofatumumab
• Prior exposure to ofatumumab or other targeted anti-CD20 therapies including rituximab
• Known HIV positivity
• Positive serology for Hepatitis B
• Positive serology for Hepatitis C
• Participants who are candidates for curative radiotherapy, unless radiation therapy is considered too toxic (as in abdominal disease), or is refused by the patient
• New York Heart Association Classification III of IV heart disease
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection that is not optimally treated with antibiotics, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant or breastfeeding women
• History of a different malignancy are ineligible except for the following circumstances: Individuals with a history of other malignancy are eligible if they have been disease-free for at least one year and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible even if diagnosed and treated within the past 1 year: localized prostate cancer, prostate cancer with elevated PSA but no measurable disease on CT scans or bone scan, cervical cancer in situ, breast ductal carcinoma in situ and non-melanoma skin cancers.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01239394
• Other Study ID Numbers: 10-271
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Jeremy Abramson, MD, Massachusetts General Hospital
• Original Responsible Party: Jeremy S. Abramson, MD, Massachusetts General Hospital
• Current Study Sponsor: Massachusetts General Hospital
• Original Study Sponsor: Same as current

Collaborators

• Dana-Farber Cancer Institute
• Beth Israel Deaconess Medical Center
• GlaxoSmithKline

Investigators

• Principal Investigator: Jeremy S. Abramson, MD; Massachusetts General Hospital

• PRS Account: Massachusetts General Hospital
• Verification Date: September 2017