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

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00274651

Acronym

PXD101-CLN-6

Enrollment

Registered

2006-01-11

Start date

2006-01-31

Completion date

2009-07-31

Last updated

2015-07-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

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

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.

Interventions

DRUGbelinostat

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Objective Response Rate in Patients With Recurrent or Refractory Cutaneous T-cell Lymphoma (CTCL)	throughout the study, or for a maximum of 2 years	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.
Objective Response Rate in Patients With Recurrent or Refractory Peripheral T-cell Lymphoma (PTCL))	throughout the study, or for a maximum of 2 years	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.

Secondary

Measure	Time frame	Description
Time to Progression	throughout the study, or for a maximum of 2 years	Time to progression was defined as the interval between the first date of treatment and the first notation of disease progression.
Time to Response	throughout the study, or for a maximum of 2 years	Time to response was defined as the interval between the first date of treatment and the first notation of response.
Duration of Response	throughout the study, or for a maximum of 2 years	Duration of response was defined as the time from first notation of response until the time of first notation of disease progression.

Countries

France, Germany, Israel, Thailand, United States

Participant flow

Participants by arm

Arm	Count
CTCL (ITT Population) CTCL patients will receive 1000 mg/m2 of PXD101 IV belinostat: 1000 mg/m2 for 5 days every 21 days; IV	29
PTCL (ITT Population) PTCL patients will receive 1000 mg/m2 of PXD101 IV belinostat: 1000 mg/m2 for 5 days every 21 days; IV	24
Total	53

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	6	3
Overall Study	Death	1	3
Overall Study	Lack of Efficacy	13	6
Overall Study	Physician Decision	8	7
Overall Study	Withdrawal by Subject	0	1

Baseline characteristics

Characteristic	CTCL (ITT Population)	PTCL (ITT Population)	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	17 Participants	12 Participants	29 Participants
Age, Categorical Between 18 and 65 years	12 Participants	12 Participants	24 Participants
Age, Continuous	64.1 years STANDARD_DEVIATION 13.4	58.8 years STANDARD_DEVIATION 15.9	61.7 years STANDARD_DEVIATION 14.7
Region of Enrollment France	2 participants	0 participants	2 participants
Region of Enrollment Germany	1 participants	0 participants	1 participants
Region of Enrollment Israel	2 participants	1 participants	3 participants
Region of Enrollment Thailand	2 participants	6 participants	8 participants
Region of Enrollment United States	22 participants	17 participants	39 participants
Sex: Female, Male Female	15 Participants	7 Participants	22 Participants
Sex: Female, Male Male	14 Participants	17 Participants	31 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	29 / 29	23 / 24
serious Total, serious adverse events	7 / 29	8 / 24

Outcome results

Primary

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.