Belinostat and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Relapsed Aggressive B-Cell Non-Hodgkin Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified December 2013 by University of Arizona
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Arizona
ClinicalTrials.gov Identifier:
NCT01686165
First received: September 12, 2012
Last updated: December 20, 2013
Last verified: December 2013
  Purpose

This study looks at what effects (good and bad) a drug called PXD-101 (belinostat) in combination with the radioactive drug Zevalin (yttrium Y 90 ibritumomab tiuxetan) has on patients with relapsed aggressive (high-risk) non-Hodgkin lymphoma. Studies in the laboratory suggest that drugs such as PXD101 can act upon specific cancer cell processes to cause either death of the cancer cells or prevention of their growth. In human studies with a small number of patients with this lymphoma, PXD-101 has shown the ability to shrink and slow tumor growth. When Zevalin is delivered directly to the tumor, the lymphoma cells are destroyed and this may result in the disappearance of the tumor (remission)


Condition Intervention Phase
Anaplastic Large Cell Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Mantle Cell Lymphoma
Drug: belinostat
Biological: rituximab
Radiation: yttrium Y 90 ibritumomab tiuxetan
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Exploratory Study of PXD-101(Belinostat) Followed by Zevalin in Patients With Relapsed Aggressive High-Risk Lymphoma

Resource links provided by NLM:


Further study details as provided by University of Arizona:

Primary Outcome Measures:
  • Complete response rate [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • Overall response [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Progression-free survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Will be estimated using a Kaplan-Meier estimate. The observed 2-year progression-free survival rate will be estimated (with a 95% confidence interval) from the Kaplan-Meier curve.

  • Occurrence of adverse events and serious adverse events [ Time Frame: Up to 30 days after patient receives last dose of study drug ] [ Designated as safety issue: Yes ]
    The proportion of patients with a given adverse event will be tabulated and the 95% confidence interval computed.


Estimated Enrollment: 13
Study Start Date: September 2012
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (belinostat, yttrium Y 90 ibritumomab tiuxetan)
Patients receive belinostat IV over 30-60 minutes on days 1-5. Treatment with belinostat repeats every 21 days for 2 courses. Patients then receive rituximab IV on days 1 and either 7, 8, or 9, and yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 50. Treatment continues in the absence of disease progression or unacceptable toxicity.
Drug: belinostat
Given IV
Other Name: PXD101
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Radiation: yttrium Y 90 ibritumomab tiuxetan
Given IV
Other Names:
  • 90Y ibritumomab tiuxetan
  • IDEC Y2B8
  • Y90 Zevalin
  • Y90-labeled ibritumomab tiuxetan

Detailed Description:

PRIMARY OBJECTIVES:

I. To document the complete response rate and overall response for patients with relapsed aggressive high-risk non-Hodgkin's lymphoma treated with two cycles PXD-101 followed by one cycle of Zevalin.

SECONDARY OBJECTIVES:

I. To estimate 2-year progression-free survival in patients with relapsed aggressive high-risk non-Hodgkin's lymphoma treated with two cycles PXD-101 followed by one cycle of Zevalin.

II. To evaluate the toxicity of two cycles PXD-101 and one cycle of Zevalin in patients with relapsed aggressive high-risk non-Hodgkin's lymphoma.

OUTLINE:

Patients receive belinostat intravenously (IV) over 30-60 minutes on days 1-5. Treatment with belinostat repeats every 21 days for 2 courses. Patients then receive rituximab IV on days 1 and either 7, 8, or 9, and yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day 50. Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 2 years and then every 6 months for 3 years.

  Eligibility

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

Inclusion Criteria:

  • Patients must have biopsy confirmed, cluster of differentiation (CD)20 positive diffuse large B-cell lymphoma, mantel cell, high grade-B-cell or anaplastic large B cell non-Hodgkin lymphoma (NHL); AND bone marrow must show =< 20% CD20+ B-cells with >= 15% cellularity within 42 days of study registration
  • Any stage disease is allowed
  • Patients must have been previously treated:

    • >= 3rd line if bone marrow transplant (BMT) candidate OR
    • >= 2nd line if not BMT candidate OR
    • >= 2nd relapse for BMT candidate OR
    • >= 1st relapse for non- BMT candidate
  • Patients must have a diagnostic quality contrast computed tomography (CT) scan of the chest, abdomen and pelvis OR baseline positron emission tomography (PET)-CT scan performed within 28 days prior to registration
  • All patients must have bidimensionally measurable disease with lesions at least 1.5 cm in one dimension all measurable disease must be assessed within 28 days of registration
  • For purposes of determining prior drug regimens the following should be used as a standard; radiation therapy counts as 1 treatment, BMT including induction counts as one treatment, radioimmunotherapy is not considered a chemotherapy regimen, rituximab alone is not considered a treatment; all prior therapy must have been completed at least 30 days prior to registration; patients should not have taken valproic acid, or any other histone deacetylase inhibitor (eg., vorinostat, romidepsin), for at least 30 days prior to registration; patients must have recovered from any toxicities related to therapies prior to registration
  • Patients must not have clinical evidence of central nervous system involvement by lymphoma, since proposed treatment would not be able to address it adequately; any laboratory (eg., lactate dehydrogenase [LDH]) or radiographic tests performed to access central nervous system (CNS) involvement must be negative and must be performed within 42 days prior to registration
  • Patients must have unilateral or bilateral bone marrow biopsy performed within 42 days prior to registration
  • Life expectancy of greater than 3 months
  • Karnofsky performance status >= 60%
  • Leukocytes >= 3,000/mcL
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
  • Total bilirubin =< 1.5 X institutional upper limit of normal (unless associated with Gilbert's syndrome)
  • Serum creatinine < 2 x institutional upper limit of normal OR
  • Measured creatinine clearance >= 60 mL/min
  • LDH < 1.50 X institutional upper limit of normal
  • Patients must have an electrocardiogram (EKG) with no significant abnormalities within 28 days prior to registration
  • The effects of PXD-101 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, the patient should inform the treating physician immediately
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Patients who have had chemotherapy or radiotherapy within 30 days (6 weeks for nitrosoureas or mitomycin C) prior to study screening or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Prior radioimmunotherapy
  • Pregnant or nursing
  • Clinical evidence of CNS involvement by lymphoma
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to PXD-101 or Zevalin or other agents used in the study
  • Concomitant medication that may cause Torsade de Pointes, i.e. prolongation of the QT interval > 500 msec
  • Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension, congestive heart failure related to primary cardiac disease, any condition requiring anti-arrhythmic therapy, ischemic or valvular heart disease, or a myocardial infarction within the past 6 months
  • Current long QT syndrome or baseline prolongation of QT/QTcF interval, i.e. demonstration of a QTcF interval > 450 msec
  • Clinical evidence of severe peripheral vascular disease, diabetic ulcers or venous stasis ulcers, or history of deep venous or arterial thrombosis within 3 months prior to screening
  • Known to be human immunodeficiency virus (HIV) positive or with known acquired immunodeficiency syndrome (AIDS) syndrome
  • Patients may not be receiving any other investigational agents
  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: NCT01686165

Contacts
Contact: Soham D Puvvada, MD sohampuvvada@email.arizona.edu
Contact: Ruth Canamar 520-626-6515 RCanamar@uacc.arizona.edu

Locations
United States, Arizona
University of Arizona Cancer Center Recruiting
Tucson, Arizona, United States, 85724-5024
Contact: SOham D Puvvada, MD       sohampuvvada@email.arizona.edu   
Contact: Ruth Canamar    (520) 626-6515    rcanamar@uacc.arizona.edu   
Principal Investigator: Soham D Puvvada         
Sponsors and Collaborators
University of Arizona
Investigators
Principal Investigator: Soham Puvvada University of Arizona
  More Information

No publications provided

Responsible Party: University of Arizona
ClinicalTrials.gov Identifier: NCT01686165     History of Changes
Other Study ID Numbers: 12-0288-04, NCI-2012-01131
Study First Received: September 12, 2012
Last Updated: December 20, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Anaplastic
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, T-Cell
Antibodies, Monoclonal
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 24, 2014