Ofatumumab and Bortezomib for Patients With Low-grade B-cell Non-hodgkin Lymphoma That Relapse After Rituximab

This study has been terminated.
(lack of accrual)
Sponsor:
Collaborators:
Rhode Island Hospital
The Miriam Hospital
Memorial Hospital of Rhode Island
Dartmouth-Hitchcock Medical Center
Information provided by (Responsible Party):
Jorge Castillo, Brown University
ClinicalTrials.gov Identifier:
NCT01119794
First received: May 6, 2010
Last updated: July 5, 2013
Last verified: July 2013
  Purpose

The purpose of this study is to: Investigate the Overall Response Rate (ORR) of the combination of ofatumumab and bortezomib in patients with low-grade B-cell non-Hodgkin lymphoma (LG-NHL) that relapse beyond 6 months of a previous rituximab-containing regimen.


Condition Intervention Phase
Lymphoma, Non-Hodgkins
Drug: Ofatumumab and Bortezomib
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Ofatumumab in Combination With Bortesomib in Patients With Relapsed or Refractory Low-Grade Non-Hodgkins Lymphoma

Resource links provided by NLM:


Further study details as provided by Brown University:

Primary Outcome Measures:
  • Measure Response Rate [ Time Frame: 13 months unless progression ] [ Designated as safety issue: Yes ]

Enrollment: 10
Study Start Date: July 2010
Estimated Study Completion Date: December 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ofatumumab IV,
Ofatumumab 1000 mg IV Cycle 1 on day 1, 8, 15 and 22,
Drug: Ofatumumab and Bortezomib
Ofatumumab 1000 mg IV Cycle 1 on day 1, 8, 15 and 22- in the induction phase Ofatumumab 1000 mg IV on day 1- will receive in the maintenance phase Patients will remain until progression

Detailed Description:

41 patients will be enrolled in this trial with low grade lymphomas and will be given Ofatumumab 1000 mg and Bortezomib IV 1.6 mg/m2 weekly times 4 treatments and will then receive maintenance treatment with the 2 agents every 2 months for 1 year unless disease progression.

  Eligibility

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

Inclusion Criteria:

  • Patients are required to have histologically confirmed lymphoma according to the WHO/Revised European-American Lymphoma classification, including B-cell small lymphocytic lymphoma (SLL); marginal zone lymphoma (MZL); follicular lymphoma (FL), grades 1, 2, or 3; mantle cell lymphoma (MCL); and Waldenström macroglobulinemia. Prior history of transformed lymphoma is permitted as long as recent biopsies revealed no evidence of aggressive lymphoma and it has been > 3years since prior aggressive lymphoma
  • Patients must measurable disease (defined as 1 cm with spiral computed tomography scan)
  • Relapse of disease beyond 6 months after rituximab-containing regimen
  • Patients had to have received no more than three prior lines of conventional cytotoxic therapy, and were required to have stopped receiving cytotoxic chemotherapy for at least 4 weeks before study enrollment
  • Absolute neutrophil count > 1,500/uL and Platelet > 100,000/uL (if known lymphomatous involvement of the bone marrow, then absolute neutrophil count > 750/uL and platelet count of > 50,000/uL) within 14 days of enrollment.
  • Total bilirubin < 1.5 x upper institutional limit of normal (ULN), and AST or ALT < 2.5 x ULN (< 3 x ULN if the patient had liver involvement); alkaline phosphatase < 2.5x upper limit of normal; and a creatinine < 2mg/dl within 14 days of enrollment.
  • ECOG performance status 0 to 2
  • Minimum life expectancy of 6 months
  • Age older than 18 years
  • Voluntary, signed written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.
  • Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study.
  • Male subject agrees to use an acceptable method for contraception for the duration of the study.

Exclusion Criteria:

  • Subjects who have current active hepatic or biliary disease asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment)
  • Documented infection with HIV
  • Positive serology for Hepatitis B defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded.
  • Central nervous system or meningeal involvement by lymphoma
  • Prior transplantation
  • Contraindication to any drug contained in the chemotherapy regimens
  • Any serious active disease or co-morbid condition that would impair protocol treatment.
  • Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal call carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy.
  • Prior treatment with any anti-CD20 monoclonal antibody, with the exception of rituximab, or any proteasome inhibitor.
  • Patient has Grade 2 peripheral neuropathy within 14 days before enrollment.
  • Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening has to be documented by the investigator as not medically relevant.
  • Patient has hypersensitivity to boron or mannitol.
  • Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum pregnancy test result obtained during screening. A pregnancy test must be performed within 7 days prior to study drug. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
  • Patient has received other investigational drugs within 4 weeks before enrollment or 5 half lives of the investigational agent.
  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  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: NCT01119794

Locations
United States, New Hampshire
Dartmouth-Hitchcock Medical Center
Hanover, New Hampshire, United States
United States, Rhode Island
Rhode Island Hospital
Providence, Rhode Island, United States, 02903
Miriam Hospital
Providence, Rhode Island, United States, 02906
Sponsors and Collaborators
Brown University
Rhode Island Hospital
The Miriam Hospital
Memorial Hospital of Rhode Island
Dartmouth-Hitchcock Medical Center
Investigators
Principal Investigator: Jorge Castillo, MD Lifespan
  More Information

No publications provided

Responsible Party: Jorge Castillo, Priniciple Investigator, Brown University
ClinicalTrials.gov Identifier: NCT01119794     History of Changes
Other Study ID Numbers: BrUOG-NHL-227
Study First Received: May 6, 2010
Last Updated: July 5, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Brown University:
B-cell small lymphocytic lymphoma
marginal zone lymphoma
follicular lymphoma
mantle cell lymphoma
Waldenström macroglobulinemia.
Low Grade B cell Non-Hodgkins Lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bortezomib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 22, 2014