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

Alternate Title

FR901228 in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Active	18 and over	NCI	MDA-2005-0579 7869, NCI-7869, NCT00383565

Objectives

1. 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.
2. 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.
3. Determine 2-year progression-free and overall survival.

Entry Criteria

Disease Characteristics:

• 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)



• No CNS lymphoma

 [Note: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.]

Prior/Concurrent Therapy:

• See Disease Characteristics
• Recovered from prior therapy
• No prior doxorubicin hydrochloride ≥ 450 mg/m² or mitoxantrone ≥ 112 mg/m²
  • Patients who received both mitoxantrone and doxorubicin hydrochloride should have a "doxorubicin equivalent dose" < 450 mg/m²
• 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

Patient Characteristics:

• ECOG performance status 0-2
• Absolute neutrophil count ≥ 1,000/mm³ OR ≥ 500/mm³ if extensive bone marrow involvement (> 50%) or hypersplenism with palpable splenomegaly
• Platelet count ≥ 75,000/mm³ OR ≥ 50,000/mm³ 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
• Creatinine normal
• Cardiac function ≥ 50% by MUGA
• 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)

Expected Enrollment

A total of 35 patients will be accrued for this study.

Outcomes

Overall objective response rate (complete response [CR] and partial response [PR]) after 6 courses of treatment

Survival time, time to disease progression, and time to treatment failure as measured by the Kaplan-Meier method
Duration of response (CR and PR)

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.

Trial Contact Information

Trial Lead Organizations

M. D. Anderson Cancer Center at University of Texas

Luis Fayad, MD, Protocol chair		Ph: 713-792-2860; 800-392-1611
Anas Younes, MD, Protocol co-chair		Ph: 713-792-2860; 800-392-1611
Jorge Romaguera, MD, Protocol co-chair		Ph: 713-792-2860; 800-392-1611 Email: jromague@mdanderson.org

U.S.A.
Texas
	Houston
	M. D. Anderson Cancer Center at University of Texas
		Clinical Trials Office - M. D. Anderson Cancer Center at the University of Texas	Ph:  713-792-3245

Registry Information
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
Trial Start Date		2006-09-20
Trial Completion Date		2008-02-27 (estimated)
Registered in ClinicalTrials.gov		NCT00383565
Date Submitted to PDQ		2006-05-15
Information Last Verified		2006-10-26
NCI Grant/Contract Number		CA16672, CM62202