Ofatumumab and Bortezomib in Treating Patients With Previously Untreated Waldenstrom Macroglobulinemia

NCT01536067 | Terminated Phase 2 Results DMC

• 2 other identifiers: I 205011NCI-2011-03816
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial studies how well giving ofatumumab together with bortezomib works in treating patients with previously untreated Waldenstrom macroglobulinemia. Monoclonal antibodies, such as ofatumumab and bortezomib, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving ofatumumab together with bortezomib may be a better way to block cancer growth

Conditions

Waldenström Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (CR + PR + MR) of Ofatumumab in Combination With Bortezomib

  Assessed using the Consensus Panel recommendations from the Third International Workshop on Waldenstrom Macroglobulinemia.

  Every 28 days

Secondary Outcomes (8)

• Frequency of Complete Remission (CR)

  Every 28 days

• Frequency of Near (n)CR

  Every 28 days

• Frequency of Very Good Partial Response (VGPR)

  Every 28 days

• Frequency of PR

  Every 28 days

• Time to Progression

  From start of treatment to disease progression, assessed up to 12 months

Study Arms (1)

Treatment (monoclonal antibody therapy)

EXPERIMENTAL

INDUCTION PHASE: Patients receive ofatumumab IV on days 1, 8, and 15 and bortezomib SC on days 8 and 15. Beginning on course 2, patients receive ofatumumab IV on days 1 and 15 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE PHASE: Beginning 8 weeks after course 4 of induction phase, patients receive ofatumumab IV on day 1 and bortezomib SC on days 1, 8, and 15. Treatment repeats every 28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

Biological: ofatumumab; Drug: bortezomib; Other: laboratory biomarker analysis

Interventions

ofatumumab BIOLOGICAL

Given IV

Also known as: Arzerra, HuMax-CD20

Treatment (monoclonal antibody therapy)

bortezomib DRUG

Given SC

Also known as: LDP 341, MLN341, VELCADE

Treatment (monoclonal antibody therapy)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (monoclonal antibody therapy)

Eligibility Criteria

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

You may qualify if:

• Diagnosis of Waldenstrom Macroglobulinemia and presence of cluster of differentiation (CD)20+ tumor cells as determined by immune-histochemistry or flow cytometric analysis in bone marrow or representative lymphoid tissue specimen; to be deemed eligible, patients must meet at least one of the following criteria:
• Rising immunoglobulin (Ig)M
• Hemoglobin =\< 10 g/dL
• Platelet count =\< 100 x 10\^9/L
• Symptomatic or bulky lymphadenopathy or organomegaly
• Systemic manifestations of Waldenstrom Macroglobulinemia (WM), such as hyperviscosity symptoms (patients with symptoms of hyperviscosity syndrome must be treated with plasmapheresis to control the syndrome prior to enrollment), neuropathy, amyloidosis, cryoglobulinemia, B-symptoms, or recurrent bleeding
• Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of =\< 2
• Have a life expectancy of \>= 3 months
• Absolute neutrophil count \>= 1.0 x 10\^9/L unless the result of disease infiltration of bone marrow
• Platelet count \>= 50 x 10\^9/L unless the result of disease infiltration of bone marrow
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 3 x the institutional upper limit of normal (ULN)
• Total bilirubin =\< 3 mg/dL or 1.5 x institutional ULN, whichever is lower
• Serum creatinine =\< 3 mg/dL
• Female patients are either post-menopausal or surgically sterilized otherwise they must agree to use acceptable contraceptive methods (e.g. double barrier) during treatment
• Male subjects, even if surgically sterilized (i.e., status post vasectomy) must agree to one of the following:

You may not qualify if:

• Pregnant and nursing female patients
• Prior anti-neoplastic therapy for WM; the use of plasmapheresis to manage the symptoms of hyperviscosity and other IgM paraprotein mediated symptoms is allowed and does not disqualify a patient from the study; if a patient undergoes plasmapheresis within 8 weeks of starting the study treatment then the IgM level prior to plasmapheresis should be used for response assessment; neoplastic use of glucocorticoids is prohibited during the screening and treatment period; patients with active hyperviscosity symptoms should not be enrolled in this study unless the symptoms resolve after plasmapheresis
• Unwilling or unable to follow protocol requirements
• Any condition which in the Investigator's opinion deems the patient an unsuitable candidate to receive study drug
• Received an investigational agent within 30 days prior to enrollment
• Known human immunodeficiency virus (HIV) positive
• Positive serology for hepatitis B (HB) defined as a positive test for hepatitis B surface antigen (HBsAg); in addition, if HBsAg is negative and hepatitis B core antibody (HBcAb) is positive, regardless of hepatitis B surface antibody (HBsAb) status, a HB deoxyribonucleic acid test will be performed and if HB DNA is positive the patient will be excluded; if a patient is HBsAg negative, HBcAb positive, and HBsAb positive, indicating past but not active infection, the patient will be included on the study
• Positive serology for hepatitis C (HC) defined as a positive test for Hep C by enzyme immunoassays (EIA), in which case reflexively perform a HC recombinant immunoblot assay (RIBA) on the same sample to confirm the result
• Diagnosis of a malignant disorder other than WM within 3 years of the study enrollment with the exception of completely resected non-melanoma skin cancer and successfully treated in-situ cancer
• Uncontrolled infection
• Hypersensitivity to bortezomib, boron, or mannitol
• Grade 2 or greater peripheral neuropathy; since WM is known to cause peripheral neuropathy (PN), if, in investigator's judgement, a patient has Grade 2 PN related to WM, then he/she can be enrolled onto the study; under no circumstances patient with greater than Grade 2 PN can be enrolled
• Myocardial infarction within 6 months of enrollment; New York Heart Association (NYHA) Class III or more heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias; arrhythmias requiring active therapy other than chronic stable atrial fibrillation; if a patient has an implanted cardiac pacemaker and is otherwise well can be enrolled onto this study after demonstrating normal ejection fraction and clearance from a cardiologist; at the time of screening any electrocardiographic abnormality has to be documented as not medically relevant by the investigator before the patient proceeds to the enrollment phase
• Any serious medical or psychiatric illness that may interfere with participation in the study
• Patients with symptoms of hyperviscosity syndrome will not be enrolled on the study until they undergo plasmapheresis that results in resolution of symptoms and optimal control of the syndrome

Sponsors & Collaborators

• Roswell Park Cancer Institute: lead
• National Cancer Institute (NCI): collaborator
• GlaxoSmithKline: collaborator

Study Sites (2)

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

ofatumumab; Bortezomib

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Senior Administrator, Compliance - Clinical Research Services
• Organization: Roswell Park Cancer Institute

716-845-2300

Study Officials

• Seema Bhat

  Roswell Park Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 10, 2012
• First Posted: February 20, 2012
• Study Start: April 1, 2012
• Primary Completion: April 1, 2014
• Last Updated: June 10, 2016
• Results First Posted: June 10, 2016

Record last verified: 2016-05

Locations

US (2)