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A Phase II Study of Suberoylanilide Hydroxamic Acid (SAHA) in Indolent Non-Hodgkin's Lymphoma

Phase 2
18 Years
Open (Enrolling)
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Nodal Marginal Zone B-cell Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma

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Trial Information

A Phase II Study of Suberoylanilide Hydroxamic Acid (SAHA) in Indolent Non-Hodgkin's Lymphoma


I. To evaluate the anti-tumor activity of SAHA as assessed by the objective response rate,
time to progression and survival in subjects with advanced lymphoma.

II. To assess the toxicity profile of SAHA in this patient population. III. To perform
correlative laboratory investigations to confirm modulation of chromatin acetylation as the
biologic target and attempt to gain insight into the downstream molecular mechanisms
involved in the induction of apoptosis mediated by SAHA.


Patients receive oral vorinostat twice daily on days 1-14. Treatment repeats every 21 days
for up to a total of 12 courses in the absence of disease progression or unacceptable

After completion of study treatment, patients are followed periodically for 3 years.

Inclusion Criteria:

- Patients must have histologically or cytologically confirmed relapsed/refractory
indolent Non-Hodgkin's Lymphoma (Included in this category are 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 CT scan. 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 SAHA); rituxan alone does not count as a regimen,
however, Bexxar or Zevalin do; the most recent therapy must have failed to induce a
complete response, 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 months posttransplant; to be eligible after either type of
transplant, patients must have achieved platelet counts greater than 100,000/mcL, and
WBC greater than 1,000/mcL at some point after their transplant, and 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

- ECOG performance status #2 (Karnofsky >= 60%)

- 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

- AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal

- Creatinine up to and including 2 mg/dl

- Premenopausal women must have a negative serum pregnancy test prior to entry on this
study; the effects of SAHA on the developing human fetus at the recommended
therapeutic dose are unknown; for this reason and because HDAC inhibitors are known
to be teratogenic, 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

Exclusion Criteria:

- Patients who have had chemotherapy within 4 weeks, Rituximab within three months
(unless there is evidence of progression) 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 SAHA; valproic acid should be stopped at least two weeks prior to
enrollment; nitrosureas 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 SAHA

- 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 or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- Pregnant women are excluded from this study because SAHA is a HDAC inhibitor agent
with the potential for teratogenic or abortifacient effects; because there is an
unknown but potential risk for adverse events in nursing infants secondary to
treatment of the mother with SAHA, breastfeeding should be discontinued if the mother
is treated with SAHA

- HIV-positive patients receiving combination antiretroviral therapy are ineligible
because of the potential for pharmacokinetic interactions with SAHA; in addition, HIV
patients not receiving combination antiretroviral therapy are also ineligible as
these patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy

- Patients with other active malignancies are ineligible for this study

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Response rate (CR+PR)

Outcome Description:

Exact binomial 95% confidence intervals will be provided.

Outcome Time Frame:

Up to 3 years

Safety Issue:


Principal Investigator

Leslie Popplewell

Investigator Role:

Principal Investigator

Investigator Affiliation:

Beckman Research Institute


United States: Food and Drug Administration

Study ID:




Start Date:

September 2005

Completion Date:

Related Keywords:

  • Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
  • Nodal Marginal Zone B-cell Lymphoma
  • Recurrent Grade 1 Follicular Lymphoma
  • Recurrent Grade 2 Follicular Lymphoma
  • Recurrent Grade 3 Follicular Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Recurrent Marginal Zone Lymphoma
  • Lymphoma
  • Lymphoma, Follicular
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell
  • Lymphoma, B-Cell, Marginal Zone
  • Lymphoma, Mantle-Cell



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