Clinical trial NCT00383565: FR901228 in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
Official title: A Phase II Study of Depsipeptide, a Histone Deacetylase Inhibitor, in Relapsed or Refractory Mantle Cell or Diffuse Large Cell Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Mantle Cell Lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2006-10-03
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: FR901228 may stop the growth of cancer cells by blocking some of the enzymes needed for cell to grow and by blocking blood flow to the cancer. This phase II trial is studying how well FR901228 works in treating patients with relapsed or refractory non-Hodgkin's lymphoma.

Detailed description: OBJECTIVES:

I. Determine the response rate (complete and partial) to FR901228 in patients with relapsed or refractory mantle cell or diffuse large cell non-Hodgkin's lymphoma.

II. Evaluate the safety and feasibility of FR901228, in terms of the incidence of toxicity and maximum grade observed and courses delayed or dose reductions, in these patients.

III. Determine 2-year progression-free and overall survival.

OUTLINE: Patients receive FR901228 IV over 4 hours on days 1, 8, and 15.

Treatment repeats every 28 days for at least 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed every 3-6 months for up to 5 years.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed aggressive B-cell non-Hodgkin's lymphoma of 1 of the following subtypes:

  * Mantle cell lymphoma
  * Diffuse large cell lymphoma
  * (Ineligible for or unwilling to undergo stem cell transplantation)
* Relapsed or refractory disease:

  * Any number of prior therapies allowed for relapsed disease, including peripheral blood stem cell or bone marrow transplantation
  * No more than 2 prior regimens, excluding monotherapy with monoclonal antibody or radiotherapy, for refractory disease
* Measurable disease, defined as \>= 1 lesion \>= 1.5 cm in the longest diameter
* No transformed lymphoma, defined as the transformation of a low-grade lymphoma, including follicular lymphoma or small lymphocytic lymphoma, to a high-grade lymphoma (e.g., diffuse large cell lymphoma)
* ECOG performance status 0-2
* Absolute neutrophil count \>= 1,000/mm\^3 OR \>= 500/mm\^3 if extensive bone marrow involvement (\> 50%) or hypersplenism with palpable splenomegaly
* Platelet count \>= 75,000/mm\^3 OR \>= 50,000/mm\^3 if extensive bone marrow involvement (\> 50%) or hypersplenism with palpable splenomegaly
* Bilirubin normal
* Alkaline phosphatase =\< 2 times upper limit of normal (ULN)
* AST =\< 2 times ULN
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No significant cardiac disease, including New York Heart Association class III-IV congestive heart failure
* No history of serious ventricular arrhythmia
* QTc \< 500 msec
* No evidence of cardiac hypertrophy on ECG
* No known HIV positivity
* No other uncontrolled serious medical condition or active infection (e.g., chronic obstructive pulmonary disease, diabetes)
* Recovered from prior therapy
* No prior doxorubicin hydrochloride \>= 450 mg/m\^2 or mitoxantrone \>= 112 mg/m\^2 (Patients who received both mitoxantrone and doxorubicin hydrochloride should have a "doxorubicin equivalent dose" \< 450 mg/m\^2
* No prior therapy with a histone deacetylase inhibitor
* No concurrent dexamethasone or prednisone except for refractory nausea/vomiting
* No concurrent drugs associated with QTc prolongation (e.g., dolasetron mesylate)
* Concurrent hydrochlorothiazide, furosemide, or other diuretics allowed provided patient is receiving potassium chloride supplementation (No supplementation needed if switched to a potassium-conserving diuretic)
* No CNS lymphoma
* Creatinine normal
* Cardiac function \>= 50% by MUGA

Primary outcomes:
measure: Overall Objective Response Rate (Complete Response [CR] and Partial Response [PR]) After 6 Courses of Treatment
timeFrame: 24 weeks (6 courses of 4 week cycles)
Secondary outcomes:
measure: Median Progression Free-survival (PFS)
timeFrame: 2 Years
measure: Median Overall Survival
timeFrame: 5 Years
Other outcomes:
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Jorge Romaguera
role: PRINCIPAL_INVESTIGATOR
References: