Ofatumumab as Primary Therapy of Chronic Graft Versus Host Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by H. Lee Moffitt Cancer Center and Research Institute
Sponsor:
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT01680965
First received: September 4, 2012
Last updated: June 11, 2014
Last verified: June 2014
  Purpose

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


Condition Intervention Phase
Chronic Graft Versus Host Disease
Drug: Ofatumumab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Ofatumumab in Combination With Glucocorticoids for Primary Therapy of Chronic Graft Versus Host Disease

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Number of participants with dose limiting toxicities [ Time Frame: within 28 days of initiation ] [ Designated as safety issue: Yes ]
    The dose limiting toxicity (DLT) will be Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0 defined grade 4 adverse events attributable to the study agent ofatumumab


Secondary Outcome Measures:
  • Participants Response Rates [ Time Frame: 6 months following initiation of Ofatumumab ] [ Designated as safety issue: No ]
    Overall response rate (ORR) at 6 months following initiation of therapy represents the composite outcome of complete and partial response


Estimated Enrollment: 50
Study Start Date: November 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Ofatumumab

Phase I:

Escalating dose of ofatumumab

Phase II:

Maximum tolerated dose (MTD) of Ofatumumab

Drug: Ofatumumab

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)


Detailed Description:

This is a phase I-II trial to examine the safety and efficacy of prednisone and escalating dose of ofatumumab for the primary therapy of chronic GVHD.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Hematopoietic cell transplantation (HCT) recipients newly requiring systemic glucocorticoid therapy (at ≥ 1mg/kg/day prednisone or equivalent) for chronic GVHD
  • Patients 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.

Exclusion Criteria:

  • 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
  • Subjects who 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-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.
  • Patients with 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.
  • 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.
  • Those patients with medical conditions that are controlled with medical therapy are eligible.
  • Clinically active Hepatitis B defined as positive HBsAg; or positive HBcAb with detectable hepatitis B virus (HBV) DNA viral load. Patients who are HBcAb with undetectable HBV DNA viremia are eligible.
  • Positive serology for hepatitis C (HC) defined as a positive test for HCAb and confirmed by HC RIBA or hepatitis C virus (HCV) RNA viral load
  • Screening laboratory value exclusion criteria:
  • platelets < 50 x 10^9/L (patients with platelet counts > 50 x 10^9/L supported by platelet transfusion are eligible)
  • neutrophils < 1.0 x 10^9/L (patients with an absolute neutrophil count > 1.0 x 10^9/L supported by growth factors are eligible)
  • creatinine > 2.0 times upper normal limit
  • total bilirubin >1.5 times upper normal limit (unless due to chronic GVHD)
  • alanine transaminase (ALT) > 2.0 times upper normal limit (unless due to chronic GVHD)
  • alkaline phosphatase > 2.5 times upper normal limit (unless due to chronic GVHD)
  • Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test at screening.
  • Women of child bearing potential must undergo pregnancy testing within 7 days of the first dose of study therapy. Women must also undergo pregnancy test at 6 months after the last dose.
  • Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy. Adequate contraception is defined as hormonal birth control, intrauterine device, double barrier method or total abstinence.
  • Male subjects unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01680965

Contacts
Contact: Joseph Pidala, MD, MS (813) 745-2556 Joseph.Pidala@moffitt.org
Contact: Michelle Burton, RN (813) 745-1537 Michelle.Burton@moffitt.org

Locations
United States, Florida
H.Lee Moffitt Cancer Center & Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Joseph Pidala, MD, MS    813-745-2556    Joseph.Pidala@moffitt.org   
Contact: Michelle Burton, RN    (813) 745-1537    Michelle.Burton@moffitt.org   
Sub-Investigator: Claudio Anasetti, MD         
Sub-Investigator: Melissa Alsina, MD         
Sub-Investigator: Ernesto Ayala, MD         
Sub-Investigator: Hugo Fernandez, MD         
Sub-Investigator: Teresa Field, MD, PhD         
Sub-Investigator: Lia Perez, MD         
Sub-Investigator: Jose Leonel Ochoa-Bayona, MD         
Sub-Investigator: Brian Betts, MD         
Sub-Investigator: Frederick Locke, MD         
Sub-Investigator: Taiga Nishihori, MD         
Sub-Investigator: Michael Nieder, MD         
Sub-Investigator: Marcie Riches, MD, MS         
Sub-Investigator: William Janssen, PhD         
Sub-Investigator: Mohamed Kharfan-Dabaja, MD         
Sub-Investigator: Asmita Mishra, MD         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Investigators
Principal Investigator: Joseph Pidala, MD, MS H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT01680965     History of Changes
Other Study ID Numbers: MCC-17071
Study First Received: September 4, 2012
Last Updated: June 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
Graft vs. Host Disease
GVHD
chronic graft versus host disease (cGVHD)
Allogeneic Transplant
Ofatumumab

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 23, 2014