Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

Suberoylanilide Hydroxamic Acid in Treating Patients With Relapsed Non-Hodgkin's Lymphoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	18 and over	NCI, Pharmaceutical / Industry	UCLA-0411065-01 MERCK-013-00, NCT00124631

Objectives

Primary

1. Determine the antitumor effectiveness of suberoylanilide hydroxamic acid, as measured by overall objective response rate, in patients with relapsed diffuse large B-cell lymphoma.

Secondary

1. Determine the duration of response and time to response in patients treated with this drug.
2. Determine progression-free survival, time to progression, and 3- and 6-month progression-free survival rates in patients treated with this drug.
3. Determine the safety of this drug in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed diffuse large B-cell lymphoma
  • De novo or transformed* disease

   [Note: *Patients with transformed diffuse large B-cell lymphoma must meet WHO criteria for diffuse large cell lymphoma on last biopsy prior to study entry AND have ≥ 1 prior histological diagnosis of follicular disease]

• Relapsed disease, defined as recurrent or progressive disease after standard first-line chemotherapy (e.g., CHOP or an anthracycline-containing regimen equivalent) AND 1 systemic salvage therapy that may have included autologous stem cell transplantation
  • Patients who are not candidates for systemic salvage and/or stem cell transplantation are eligible
• Must have had a response that lasted ≥ 3 months OR stable disease that lasted ≥ 3 months after completion of the most recent treatment
• Failed no more than 3 prior treatment regimens
  • Pre-induction chemotherapy and autologous stem cell transplantation are considered 1 therapy
  • Antibody therapy (e.g., rituximab) given in combination with or as consolidation therapy after a chemotherapy regimen (without intervening relapse) is considered 1 therapy
  • Antibody therapy given as a single agent is considered 1 therapy
• Measurable disease, defined as 1 unidimensionally measurable lesion ≥ 2 cm by conventional CT scan OR ≥ 1 cm by spiral CT scan
• No active brain or leptomeningeal metastases, as indicated by positive cytology from lumbar puncture or CT scan or MRI
  • Previously treated CNS disease allowed provided there is negative cytology from lumbar puncture
• No known HIV-related malignancy

Prior/Concurrent Therapy:

Biologic therapy

• See Disease Characteristics
• At least 4 weeks since prior biologic therapy
• No prior allogeneic stem cell transplantation
• No concurrent prophylactic growth factors
• No concurrent anticancer biologic therapy

Chemotherapy

• See Disease Characteristics
• At least 4 weeks since prior chemotherapy
• No concurrent anticancer chemotherapy

Endocrine therapy

• Concurrent systemic steroids allowed provided the dosage has been stabilized to the equivalent of ≤ 10 mg/day of prednisone for ≥ 4 weeks prior to study entry

Radiotherapy

• At least 4 weeks since prior radiotherapy
• No concurrent anticancer radiotherapy

Surgery

• At least 4 weeks since prior major surgery
• No prior gastrointestinal resection or procedure that may affect drug absorption

Other

• Recovered from prior therapy
• At least 4 weeks since prior investigational therapy
• No prior histone deacetylase inhibitors (e.g., FR901228, MS-275, or LAQ-824)
• No concurrent vitamins except a single daily multivitamin
• No other concurrent investigational anticancer therapy

Patient Characteristics:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count ≥ 1,000/mm³
• Platelet count ≥ 75,000/mm³

Hepatic

• Bilirubin < 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2.5 times ULN (5 times ULN if liver is involved by tumor)
• No active hepatitis B or C infection

Renal

• Not specified

Cardiovascular

• No symptomatic congestive heart failure
• No unstable angina pectoris
• No cardiac arrhythmia

Immunologic

• No acute infection requiring IV antibiotics or antiviral or antifungal agents within the past 2 weeks
• No ongoing or active infection
• No known HIV positivity
• No known allergy to any component of the study drug
• No acute or chronic graft-vs-host disease

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective double-barrier contraception during and for 14 days after completion of study treatment
• No other malignancy within the past 5 years except basal cell carcinoma or carcinoma in situ of the cervix
• No psychiatric illness or social situation that would preclude study compliance
• No other uncontrolled illness
• No circumstance that would preclude study participation

Expected Enrollment

A total of 50 patients will be accrued for this study within approximately 1 year.

Outcomes

Objective tumor response as assessed by positron emission tomography with fludeoxyglucose (FDG-PET) and the International Workshop Standardized Criteria for Non-Hodgkin's lymphoma
Measurability of tumor lesions as assessed by FDG-PET and CT scan at baseline

Duration of overall response
Progression-free survival (PFS)
Time to progression
Time to response
PFS rate at 3 and 6 months

Outline

This is an open-label, multicenter study.

Patients receive oral suberoylanilide hydroxamic acid twice daily on days 1-14. Treatment repeats every 21 days for up to 8 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed within 4 weeks and then every 6-12 months thereafter.

Trial Contact Information

Trial Lead Organizations

Jonsson Comprehensive Cancer Center at UCLA

Sven De Vos, MD, Protocol chair		Ph: 310-267-2756 Email: devos@mednet.ucla.edu

Registry Information
Official Title		A Phase II Clinical Trial of Oral Suberoylanilide Hydroxamic Acid (L-001079038) in Patients With Relapsed Diffuse Large B-Cell Lymphoma (DLBCL)
Trial Start Date		2005-05-17
Registered in ClinicalTrials.gov		NCT00124631
Date Submitted to PDQ		2005-06-09
Information Last Verified		2007-01-31
NCI Grant/Contract Number		CA16042

Back to Top