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

NCT00274651 | Terminated Phase 2 Results

• 1 other identifier: PXD101-CLN-6
• Study Type: interventional
• Target: 53
• Locations: 5 countries
• Sites: 15

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

Keywords

CTCL; PTCL; lymphoma; Non-Hodgkin's Lymphoma; Cutaneous T-Cell Lymphomas (CTCL); Peripheral T-Cell Lymphomas (PTCL); Other Types of Non-Hodgkin's Lymphoma; belinostat

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate in Patients With Recurrent or Refractory Cutaneous T-cell Lymphoma (CTCL)

  Tumor response was assessed using Cheson (Cheson 2007) and SWAT criteria. The SWAT score represents the product of the percentage total body surface area (TBSA) involvement of each lesion type (patch, plaque, and tumor or ulceration), multiplied by a weighting factor.

  throughout the study, or for a maximum of 2 years

• Objective Response Rate in Patients With Recurrent or Refractory Peripheral T-cell Lymphoma (PTCL))

  Tumor response was assessed using the revised criteria of Cheson (Cheson 2007).Tumor assessments were done using conventional radiographic methods, e.g. CT or CT/PET.

  throughout the study, or for a maximum of 2 years

Secondary Outcomes (3)

• Time to Progression

  throughout the study, or for a maximum of 2 years

• Time to Response

  throughout the study, or for a maximum of 2 years

• Duration of Response

  throughout the study, or for a maximum of 2 years

Study Arms (2)

Arm A

EXPERIMENTAL

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

Drug: belinostat

Arm B

EXPERIMENTAL

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

Drug: belinostat

Interventions

belinostat DRUG

Also known as: PXD101

Arm A; Arm B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Valerio Therapeutics: lead

Study Sites (15)

Leland Stanford Junior University

Stanford, California, 94305, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06520, United States

Location

Kansas City Cancer Center

Lenexa, Kansas, 66214, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Boston University Medical Center

Boston, Massachusetts, 02118, United States

Location

NYU Medical Center

New York, New York, 10016, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Hopitaux du Haut Leveque

Pessac, 33604, France

Location

Hospital Purpan

Toulouse, 31059, France

Location

Universitatsklinikum Essen

Essen, 45147, Germany

Location

Hadassah University Hospital Ein Kerem

Jerusalem, 91120, Israel

Location

Rabin Medical Center

Petah Tikva, 49100, Israel

Location

Songklanagarind Hospital, Prince of Songkla University

Hat Yai, 90110, Thailand

Location

King Chulalongkorn Memorial Hospital

Patumwan, 10330, Thailand

Location

Related Publications (1)

• 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.

  PMID: 25404094 DERIVED

MeSH Terms

Conditions

Lymphoma, T-Cell, Cutaneous; Lymphoma, T-Cell, Peripheral; Lymphoma, Non-Hodgkin; Lymphoma

Interventions

belinostat

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: PRS Admnistrator Gunilla Emanuelson
• Organization: Topotarget A/S

enquiries@topotarget.com

+45 39 17 83 92

Study Officials

• e-mail contact via enquiries@topotarget.com

  Valerio Therapeutics

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2006
• First Posted: January 11, 2006
• Study Start: January 1, 2006
• Primary Completion: July 1, 2009
• Study Completion: July 1, 2009
• Last Updated: July 28, 2015
• Results First Posted: October 27, 2014

Record last verified: 2015-07

Locations

FR (2); DE (1); US (8); IL (2); TH (2)