Vorinostat, Rituximab, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Lymphoma or Previously Untreated T-Cell Non-Hodgkin Lymphoma or Mantle Cell Lymphoma
A Phase I/II Study of Vorinostat Plus Rituximab, Ifosphamide, Carboplatin, and Etoposide for Patients With Relapsed or Refractory Lymphoid Malignancies or Untreated T- or Mantle Cell Lymphoma
2 other identifiers
interventional
29
1 country
1
Brief Summary
This phase I/II trial is studying the side effects and best dose of vorinostat when given together with rituximab, ifosfamide, carboplatin, and etoposide and to see how well they work in treating patients with relapsed or refractory lymphoma or previously untreated T-cell non-Hodgkin lymphoma or mantle cell lymphoma. Vorinostat may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, 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. Drugs used in chemotherapy, such as ifosfamide, carboplatin, and etoposide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving vorinostat together with rituximab and combination chemotherapy may kill more cancer cells
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2007
CompletedFirst Submitted
Initial submission to the registry
January 24, 2008
CompletedFirst Posted
Study publicly available on registry
January 28, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2010
CompletedResults Posted
Study results publicly available
May 25, 2017
CompletedMay 25, 2017
April 1, 2017
2.5 years
January 24, 2008
April 17, 2017
April 17, 2017
Conditions
Outcome Measures
Primary Outcomes (4)
Maximum Tolerated Dose of Vorinostat
28 days post last dose of study drug
Safety and Toxicity According to CTCAE v3.0
Common dose limiting toxicities.
3-5 weeks post end of treatment
Efficacy (Response Rate) of Vorinostat Combined With RICE Chemotherapy
3-5 weeks post end of treatment
Ability to Proceed to Peripheral Blood Stem Cell Collection Following Treatment
1-3 weeks post end of treatment
Study Arms (1)
Treatment (enzyme inhibitor, monoclonal antibody, chemotherapy
EXPERIMENTALPatients receive vorinostat PO QD on days 1-5, ifosfamide IV continuously over 24 hours and carboplatin IV over 1 hour on day 4, and etoposide IV over 1 hour on days 3-5. Patients who are CD20+ also receive rituximab IV once on day 3, 4, or 5. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity.
Interventions
Given PO
Given IV
Given IV
Given IV
Given IV
Correlative studies
Correlative studies
Correlative studies
Eligibility Criteria
You may qualify if:
- Patients must have relapsed or primary refractory lymphoid malignancy (including B-cell, T-cell, or Hodgkins disease), or untreated T-NHL or MCL
- Patients with other lymphomas that have not received any prior therapy and are not candidates for anthracycline-based therapies, are eligible with PI review and approval
- Revised European American classification (REAL), or World Health Organization (WHO) classification of patient's malignancies must be provided
- Patients must have measurable disease defined as lesions that can be accurately measured in two dimensions by computed tomography (CT), magnetic resonance imaging (MRI), medical photograph (skin or oral lesion), plain x-ray, or other conventional technique and a greatest transverse diameter of 1 cm or greater; or palpable lesions with both diameters \>= 2 cm
- Patients must have a bone marrow aspirate and biopsy within 28 days of enrollment and no intervening anticancer therapy
- Patients must have a CT of chest, abdomen, and pelvis within 28 days of enrollment; patients with evidence of adenopathy in the neck must have a CT of neck
- Patients should not have evidence of active central nervous system lymphoma
- Electrocardiogram (EKG) must be free of any arrhythmias (excluding sinus arrhythmia or infrequent premature ventricular contractions)
- Patients must have a Southwest Oncology Group (SWOG) performance status of 0, 1, or 2
- Absolute neutrophil count (ANC) \>= 1,500/mm\^3
- Serum creatinine \< 1.5 mg/dl or creatinine clearance greater than 60/ ml per minute by the following formula (all tests must be performed within 28 days prior to registration)
- Total bilirubin \< 1.5 times upper limit of normal, aspartate aminotransferase (AST) \< 5 times upper limit of normal
- Patients must have a serum lactate dehydrogenase (LDH) performed within 14 days prior to registration
- All patients must be informed of the investigational nature of this study and have given written consent in accordance with institutional and federal guidelines
- Patients must be anticipated to complete at least 2 cycles of chemotherapy
- +1 more criteria
You may not qualify if:
- Patients known to be human immunodeficiency virus (HIV) positive
- Pregnant or nursing women; men or women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method
- Patients with other prior malignancies except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, cervical cancer in situ, or other cancer from which the patient has been disease free for 5 years or greater, unless approved by the protocol Chair or Co-Chair
- Patients that are refractory (i.e. not responded or progressed within 6 months) to a carboplatin, cisplatin, ifosfamide, or etoposide-based regimen-based regimen
- Patients that have other medical conditions that would contraindicate treatment with aggressive chemotherapy (including active infection, uncontrolled hypertension, congestive heart failure, unstable angina pectoris, or myocardial infarction within the past 6 months, or uncontrolled arrhythmia)
- Patients with a history of impaired cardiac status (including history of severe coronary artery disease, cardiomyopathy, congestive heart failure or arrhythmia); if the patient's history is questionable, a measurement of left ventricular ejection fraction should be obtained within 42 days prior to registration; patients with left ventricular ejection fraction \< 50% are not eligible
- Autologous or allogeneic transplantation within 12 months or radioimmunotherapy within 6 months of registration
- No concurrent treatment with valproic acid or on valproic acid within 2 weeks of study enrollment
- No prior treatment with histone deacetylase inhibitors
- No concurrent therapy for this malignancy
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University of Washingtonlead
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Puget Sound Oncology Consortium
Seattle, Washington, 98109, United States
Related Publications (1)
Budde LE, Zhang MM, Shustov AR, Pagel JM, Gooley TA, Oliveira GR, Chen TL, Knudsen NL, Roden JE, Kammerer BE, Frayo SL, Warr TA, Boyd TE, Press OW, Gopal AK. A phase I study of pulse high-dose vorinostat (V) plus rituximab (R), ifosphamide, carboplatin, and etoposide (ICE) in patients with relapsed lymphoma. Br J Haematol. 2013 Apr;161(2):183-91. doi: 10.1111/bjh.12230. Epub 2013 Jan 29.
PMID: 23356514BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Ajay Gopal
- Organization
- Fred Hutchinson Cancer Research Center
Study Officials
- PRINCIPAL INVESTIGATOR
Lihua Budde
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Investigator
Study Record Dates
First Submitted
January 24, 2008
First Posted
January 28, 2008
Study Start
December 1, 2007
Primary Completion
June 1, 2010
Last Updated
May 25, 2017
Results First Posted
May 25, 2017
Record last verified: 2017-04