A Phase II Clinical Trial of PXD101 in Patients With Recurrent or Refractory Cutaneous and Peripheral T-Cell Lymphomas

NCT ID: NCT00274651

Last Updated: 2015-07-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 53 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-01-31
• Study Completion Date: 2009-07-31

Brief Summary

Open-label, non-randomized trial to assess the effectiveness of PXD101 in patients with recurrent or refractory cutaneous or peripheral and other types of T-cell lymphomas. PXD101 is a new, potent histone deacetylase (HDAC) inhibitor. Patients are treated with belinostat(PXD101) 1000 mg/m2 on days 1-5 of a 21 day cycle.

Conditions

Cutaneous T-Cell Lymphoma; Peripheral T-Cell Lymphoma; Non-Hodgkin's Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A

PXD101 1000 mg/m2 once daily for 5 days every 21 days

Group Type: EXPERIMENTAL

belinostat

Intervention Type: DRUG

Arm B

PXD101 1000 mg/m2 once daily for 5 days every 21 days

Group Type: EXPERIMENTAL

belinostat

Intervention Type: DRUG

Interventions

belinostat

Intervention Type: DRUG

Other Intervention Names

PXD101

Eligibility Criteria

Inclusion Criteria

• Male or female with age > or = 18 years.
• Histologically confirmed diagnosis of cutaneous T-cell lymphoma (CTCL) or peripheral T-cell lymphoma (PTCL) or other T-cell non-Hodgkin's lymphoma (NHL).
• Must have failed at least one line of prior systemic therapy. No limitation in number of prior therapies. CTCL patients who are refractory or intolerant to oral Targretin are also eligible.
• The presence of measurable disease (defined as > or = 1 cm with radiographic imaging) for PTCL or stage 1B or greater disease for CTCL and assessable by the severity-weighted assessment tool (SWAT).
• Adequate bone marrow and hepatic function including the following:

• Absolute neutrophil count > or = 1,000 cells/mm3, platelets > or = 40,000/mm3
• Total bilirubin < or = 1.5 x upper normal limit or < or = 3 x upper normal limit if hepatic involvement
• AST (SGOT) (aspartate aminotransferase), ALT (SGPT) (alanine aminotransferase) < or = 2.5 x upper normal limit (< or = 5 x upper normal limit if hepatic involvement)
• Hemoglobin > or = 9.0 g/dL.
• Serum potassium within normal range.
• Karnofsky performance status > or = 70%.
• Estimated life expectancy > 3 months.
• Signed informed consent approved by the Institutional Review Board (IRB).

Exclusion Criteria

• Anti-cancer therapies within 4 weeks of first PXD101 administration should be excluded unless toxicity from prior anti-cancer therapy has resolved or returned to baseline and cancer disease status warrants.
• Any use of investigational drugs within 4 weeks prior to study registration.
• Major surgery within 4 weeks of study drug administration.
• Prior allogeneic bone marrow transplant.
• A diagnosis of adult T-cell lymphoma/leukemia (ATLL) or precursor T-lymphoblastic lymphoma.
• Co-existing active infection or any co-existing medical condition likely to interfere with trial procedures. However, patients with progressing CTCL whose open skin lesions are frequently infected may not be excluded from this trial at the discretion of Investigators.
• Clinically significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension, and congestive heart failure related to primary cardiac disease, a condition requiring anti-arrhythmic therapy, history of sustained ventricular tachycardia, history of ventricular fibrillation or Torsade de Pointes, bradycardia (HR<50bpm) with or without a pacemaker, bifascicular block with a right bundle branch block and a left anterior block, ischemic or severe valvular heart disease, a myocardial infarction within 6 months or a left ventricular ejection fraction < 40% (by echocardiogram [ECHO] or multigated acquisition scan [MUGA]) within 3 months of study enrolment.
• A marked baseline prolongation of QT/QTc ((corrected) QT) interval, e.g., repeated demonstration of a QTc interval > 450 milliseconds (msec). Long QT Syndrome; the required use of concomitant medication on belinostat infusion days that may cause Torsade de Pointes.
• Renal insufficiency defined as a calculated creatinine clearance of < 45 mL/min/1.73 m2.
• A history of allergic reactions attributed to compounds of similar chemical or biological composition to PXD101 and L-arginine.
• Clinically significant central nervous system disorders with altered mental status or psychiatric disorders precluding understanding of the informed consent process and/or completion of the necessary studies.
• Patients requiring treatment for other malignant diseases or less than 5 years post-treatment completion for an invasive malignant disease (excluding non-melanotic skin cancers or cervical cancer in-situ). Patients with any history of melanoma should be excluded.
• Pregnant or breast-feeding women, and women of childbearing age and potential, who are not willing to use effective contraception. Male patients and/or their fertile female partners who are not willing to use contraceptives during the trial.
• Known infection with HIV, human T-cell leukemia virus type-1 (HTLV-1), hepatitis B or hepatitis C.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Valerio Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

e-mail contact via enquiries@topotarget.com

Role: STUDY_DIRECTOR

Valerio Therapeutics

Locations

Leland Stanford Junior University

Stanford, California, United States

Yale University School of Medicine

New Haven, Connecticut, United States

Kansas City Cancer Center

Lenexa, Kansas, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Boston University Medical Center

Boston, Massachusetts, United States

NYU Medical Center

New York, New York, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

MD Anderson Cancer Center

Houston, Texas, United States

Hopitaux du Haut Leveque

Pessac, , France

Hospital Purpan

Toulouse, , France

Universitatsklinikum Essen

Essen, , Germany

Hadassah University Hospital Ein Kerem

Jerusalem, , Israel

Rabin Medical Center

Petah Tikva, , Israel

Songklanagarind Hospital, Prince of Songkla University

Hat Yai, , Thailand

King Chulalongkorn Memorial Hospital

Patumwan, , Thailand

Countries

United States; France; Germany; Israel; Thailand

References

Foss F, Advani R, Duvic M, Hymes KB, Intragumtornchai T, Lekhakula A, Shpilberg O, Lerner A, Belt RJ, Jacobsen ED, Laurent G, Ben-Yehuda D, Beylot-Barry M, Hillen U, Knoblauch P, Bhat G, Chawla S, Allen LF, Pohlman B. A Phase II trial of Belinostat (PXD101) in patients with relapsed or refractory peripheral or cutaneous T-cell lymphoma. Br J Haematol. 2015 Mar;168(6):811-9. doi: 10.1111/bjh.13222. Epub 2014 Nov 17.

Reference Type: DERIVED

PMID: 25404094 (View on PubMed)

Other Identifiers

PXD101-CLN-6

Identifier Type: -

Identifier Source: org_study_id