LymphomaPhase 2NCT00720876
Vorinostat and Rituximab in Treating Patients With Indolent Non-Hodgkin Lymphoma
A Phase 2 study testing rituximab and vorinostat in people with Lymphoma, run by City of Hope Medical Center at 3 sites in United States.
Trial summary
RATIONALE: 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lymphoma
- What is being tested?
- rituximab and vorinostat
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 3 sitesUnited States
- Study dates
- 23 Jul 2008to 8 Jun 2017
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically or cytologically confirmed indolent Non-Hodgkin's Lymphoma; included in this category are newly diagnosed or relapsed/refractory follicular center lymphomas grade I, II, III, relapsed/refractory marginal zone B-cell lymphoma (nodal and extranodal), relapsed/refractory mantle cell lymphoma
- Patients must have measurable disease by computed tomography (CT) scan; positron emission tomography (PET) scan evaluations are desirable but not mandatory, so that patients with negative PET scans but measurable disease by CT are eligible
- Patients may have had up to four prior chemotherapeutic regimens; steroids alone and local radiation do not count as regimens (radiotherapy must have been completed at least 14 days prior to starting vorinostat); Rituxan alone does not count as a regimen; however, Bexxar or Zevalin do; for treated patients, the most recent therapy must have failed to induce a complete response (i.e., there is persistent disease by CT or PET), or there must be disease progression or recurrence after the most recent therapy
- Patients may be enrolled who relapse after autologous stem cell transplant if they are at least three months after transplant, and after allogeneic transplant if they are at least six month post transplant; to be eligible after either type of transplant, patients should have no active related infections (i.e., fungal or viral); in the case of allogeneic transplant relapse, there should be no active acute graft versus host disease (GvHD) of any grade, and no chronic graft versus host disease other than mild skin, oral, or ocular GvHD not requiring systemic immunosuppression
- Life expectancy of greater than 3 months
- Eastern Cooperative Oncology Group (ECOG) performance status 2 (Karnofsky >= 60%)
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- Absolute neutrophil count >= 1,000/mcL
- Platelets >= 100,000/mcL
- Total bilirubin within normal institutional limits; patients with elevation of unconjugated bilirubin alone, as in Gilbert's disease, are eligible
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
- Creatinine up to and including 2 mg/dl
- Pre-menopausal women must have a negative serum pregnancy test prior to entry on this study; 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 participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Patients who have had chemotherapy within 4 weeks, or radiotherapy within 2 weeks or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier are excluded; this does not include use of steroids, which may continue until two days prior to enrollment; low dose chlorambucil should be stopped two weeks prior to beginning vorinostat; valproic acid should be stopped at least two weeks prior to enrollment; nitrosoureas and mitomycin should be stopped 6 weeks prior to enrollment
- Patients may not be receiving any other investigational agents
- Patients with known brain metastases are excluded from this clinical trial unless the metastases are controlled after therapy and have not been treated with steroids within the past two months
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat
- There must be no plans for the patient to receive concurrent hormonal, biological, or radiation therapy
- Uncontrolled intercurrent illness including, but not limited to, ongoing active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
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- Pregnant women are excluded from this study; breastfeeding should be discontinued if mother is treated with vorinostat
- Human immunodeficiency virus (HIV)-positive patients receiving combination antiretroviral therapy are ineligible; in addition, HIV patients not receiving combination antiretroviral therapy are also ineligible
- Patients with other active malignancies are ineligible for this study
- Patients with preexisting or previous coagulation issues are not excluded from study as long as 1) previous pulmonary embolism or deep vein thrombosis have been adequately treated or 2) if they are actively receiving Coumadin or lovenox for anticoagulation; patients who are already on coumadin or lovenox do not need to take additional 40 mg subcutaneous injections daily
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Tower Cancer Research Foundation
Beverly Hills, California, 90211
City of Hope Comprehensive Cancer Center
Duarte, California, 91010-3000
City of Hope Medical Group
Pasadena, California, 91105
About this study
Official title: A Phase II Study of Vorinostat (Suberoylanilide Hydroxamic Acid) Plus Rituximab in Indolent Non-Hodgkin's Lymphoma
RATIONALE: 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. Giving vorinostat together with rituximab may kill more cancer cells.
PURPOSE: This phase II trial is studying the side effects of giving vorinostat together with rituximab and to see how well it works in treating patients with indolent non-Hodgkin lymphoma.
Read the detailed description
OBJECTIVES:
- To evaluate the anti-tumor activity of vorinostat and rituximab, in terms of objective response rate, time to progression, and survival, in patients with indolent non-Hodgkin lymphoma.
- To assess the toxicity profile of this regimen in these patients.
OUTLINE: Patients receive oral vorinostat twice daily on days 1-14 and rituximab IV on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed periodically.
- Conditions
- Lymphoma
- Being tested
- rituximab, vorinostat
- Keywords
- contiguous stage II grade 1 follicular lymphoma, contiguous stage II grade 2 follicular lymphoma, contiguous stage II grade 3 follicular lymphoma, noncontiguous stage II grade 1 follicular lymphoma, noncontiguous stage II grade 2 follicular lymphoma, noncontiguous stage II grade 3 follicular lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, stage I grade 1 follicular lymphoma, stage I grade 2 follicular lymphoma, stage I grade 3 follicular lymphoma, stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage III grade 3 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma, stage IV grade 3 follicular lymphoma, contiguous stage II marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- Medical subject headings
- Lymphoma, Lymphoma, Follicular, Lymphoma, B-Cell, Marginal Zone, Lymphoma, Mantle-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rituximabBiological
Rituximab will be administered at a dose of 375 mg/m2 on day 1 of every cycle, every 3 weeks.
vorinostatDrug
200 mg twice daily, orally for 14 days followed by a seven day break on a 21 day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Vorinostat and Rituximab | Experimental | Vorinostat by mouth two times (2X) per day for two weeks followed by one week of rest. Rituximab intravenously once every three weeks . Receives: Biological: rituximab; Drug: vorinostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (Complete and Partial Response)
Response was assessed according to the 2007 Cheson criteria using CT scans or PET: Complete Response (CR), Disappearance of all evidence of disease; Partial Response (PR), >=50% decrease in the Sum of the Product of Diameters (SPD) of up to 6 largest dominant masses and no increase in the size of other nodes; Overall Response (OR) = CR + PR.
Measured: After every 3 cycles, up to 1 year after the start of treatment
Secondary outcomes (2)
Progression-free Survival
Progression\Relapse is defined using the 2007 Cheson criteria, as appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy; or at least a 50% increase for nadir in the SPD of any previously involved nodes; or at least a 50% increase in the longest diameter of any singe previously identified node more than 1 cm in its short axis. Estimated using the product-limit method of Kaplan and Meier.
Measured: Until disease progress\relapse, up to 1 year after the start of treatment
Number of Participants With Grade 3 and 4 Toxicities
Grade 3 \& 4 toxicities at least possible related to study drugs during any cycle of treatment. Toxicity graded according to Common Terminology Criteria for Adverse Events version 3.0.
Measured: 3 weeks after the stop of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2008 (estimated)
- Study start23 Jul 2008
- Primary completion8 Jun 2017
- Study completion8 Jun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for LymphomaStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Robert Chen, MD, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00720876
- Sponsor's protocol ID
- 07195
- Other IDs
- P30CA033572, CDR0000600989, NCI-2010-00531
- Status last verified
- Jul 2018
- First submitted
- 22 Jul 2008
- Last updated
- 7 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Chen R, Frankel P, Popplewell L, Siddiqi T, Ruel N, Rotter A, Thomas SH, Mott M, Nathwani N, Htut M, Nademanee A, Forman SJ, Kirschbaum M. A phase II study of vorinostat and rituximab for treatment of newly diagnosed and relapsed/refractory indolent non-Hodgkin lymphoma. Haematologica. 2015 Mar;100(3):357-62. doi: 10.3324/haematol.2014.117473. Epub 2015 Jan 16.
PubMed 25596263