Ofatumumab as Primary Therapy of Chronic Graft Versus Host Disease

NCT01680965 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: MCC-17071
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 4

Brief Summary

To study the safety and side effects of Ofatumumab in the treatment of chronic graft-versus-host disease (GvHD). This study will also evaluate effectiveness of Ofatumumab when added to standard steroid treatment for chronic graft-versus-host disease

Conditions

Chronic Graft Versus Host Disease

Keywords

Graft vs. Host Disease; GVHD; chronic graft versus host disease (cGVHD); Allogeneic Transplant; Ofatumumab

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose of Ofatumumab

  Maximum Tolerated Dose was determined by increasing doses, beginning at 300 mg on day 0 and day 14, then increasing to 700 mg on day 0 and day 14 and finally 1000 mg on day 0 and day 14.

  within 21 days of initiation

• Participants Response Rates

  Overall response rate (ORR) at 6 months following initiation of therapy. ORR is the composite outcome of complete response and partial response

  6 months following initiation of Ofatumumab

Secondary Outcomes (1)

• Overall Survival (OS) at 24 Months

  Up to 24 months

Study Arms (1)

Ofatumumab

EXPERIMENTAL

Phase I: Escalating dose of ofatumumab Phase II: Maximum tolerated dose (MTD) of Ofatumumab

Drug: Ofatumumab

Interventions

Ofatumumab DRUG

Phase I: test an escalating dose of ofatumumab at cohorts of 300 mg, 700 mg, and 1000 mg given on day 0 and 14 of study. Phase II: Ofatumumab MTD on day 0 and 14; patients will be followed for total of 24 months (months 1, 3, 6, 12 after therapy, then at 18 and 24 months following therapy)

Ofatumumab

Eligibility Criteria

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

You may qualify if:

• Hematopoietic cell transplantation (HCT) recipients newly requiring systemic glucocorticoid therapy (at ≥ 1mg/kg/day prednisone or equivalent) for chronic GVHD
• Participants can be enrolled and begin study therapy with ofatumumab within 14 days from initiation of 1 mg/kg/day prednisone for therapy of chronic GVHD.

You may not qualify if:

• Relapse of primary hematologic malignancy that served as indication for HCT.
• Previous systemic glucocorticoid therapy (at ≥ 1mg/kg/day prednisone or equivalent) for chronic GVHD
• Prior systemic glucocorticoid therapy for acute GVHD is permitted
• Prior or ongoing systemic immune suppressive agents (including, but not limited to common examples such as calcineurin inhibitors, sirolimus, mycophenolate mofetil) provided for either prevention or treatment of acute GVHD are permitted and part of routine standard of care
• Current active hepatic or biliary disease (with exception of liver disease secondary to chronic GVHD, or patients with Gilbert's syndrome, asymptomatic gallstones, or stable chronic liver disease per investigator assessment).
• Patients with abnormal liver function tests due to chronic GVHD are specifically not excluded from the study. This is a common manifestation of chronic GVHD, and thus a major target for the study therapy.
• Treatment with experimental non-FDA approved therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer
• Other past or current solid tumor malignancy
• Have been free of malignancy for at least 5 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible.
• Prior treatment with anti-cluster of differentiation antigen 20 (CD20) monoclonal antibody or alemtuzumab within 3 months prior to start of therapy.
• Uncontrolled infectious complications not responsive to appropriate antimicrobial therapy.
• History of significant cerebrovascular disease (i.e. stroke or TIA) in the past 6 months or ongoing event with active symptoms or sequelae
• HIV positivity
• Uncontrolled, current significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to randomization, congestive heart failure (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities.
• A history of cardiac disease, such as coronary disease, arrhythmia or congestive heart failure that are on appropriate medical therapy and without evidence of current decompensation are eligible.

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead

Study Sites (4)

Mayo Clinic Cancer Center

Phoenix, Arizona, 85054, United States

Location

H.Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Lazaryan A, Lee S, Arora M, Kim J, Betts BC, Khimani F, Nishihori T, Bejanyan N, Liu H, Kharfan-Dabaja MA, Locke FL, Gonzalez R, Jain MD, Davila ML, Perez LE, Mishra A, Perez Perez A, Balke K, Ayala E, Ochoa L, Castaneda Puglianini O, Faramand R, Alsina M, Elmariah H, Nieder ML, Fernandez H, Anasetti C, Pidala JA. A phase 2 multicenter trial of ofatumumab and prednisone as initial therapy for chronic graft-versus-host disease. Blood Adv. 2022 Jan 11;6(1):259-269. doi: 10.1182/bloodadvances.2021005552.

  PMID: 34649279 DERIVED

Related Links

• H.Lee Moffitt Cancer Center \& Research Institute

MeSH Terms

Conditions

Bronchiolitis Obliterans Syndrome; Graft vs Host Disease

Interventions

ofatumumab

Condition Hierarchy (Ancestors)

Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Immune System Diseases

Results Point of Contact

• Title: Joseph Pidala, M.D., PhD
• Organization: Moffitt Cancer Center

Joseph.Pidala@moffitt.org

813-745-2069

Study Officials

• Joseph Pidala, MD, MS

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2012
• First Posted: September 7, 2012
• Study Start: November 14, 2012
• Primary Completion: August 1, 2020
• Study Completion: August 30, 2020
• Last Updated: October 6, 2022
• Results First Posted: November 12, 2020

Record last verified: 2022-09

Locations

US (4)