Vorinostat (MK-0683) Phase I Study in Cutaneous T-Cell Lymphoma (CTCL) Patients (MK-0683-089 EXT1)

• Sponsor: Merck Sharp & Dohme Corp. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00771472
• Collaborator: (none)
• Enrollment: 10
• Arm: 1
• Duration (Months): 35

Study Details

Study Description

Brief Summary

Part I evaluates the safety, tolerability and pharmacokinetics (PK) of vorinostat in Japanese patients with relapsed or refractory CTCL. Part II evaluates the safety of vorinostat in Japanese pts. with relapsed or refractory CTCL. Relapsed or refractory CTCL patients will be newly enrolled in Part II.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Drug: vorinostat	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase I Clinical Study of MK-0683 in Patients With Relapsed or Refractory Cutaneous T-Cell Lymphoma (CTCL)
• Study Start Date: Aug 1, 2008
• Actual Primary Completion Date: Jul 1, 2011
• Actual Study Completion Date: Jul 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vorinostat	Drug: vorinostat; Parts I & II: Vorinostat (400 mg) Oral, daily (QD). Treatment period is 28 days per cycle.; Other Names: MK-0683 Zolinza

Outcome Measures

Primary Outcome Measures

1. Parts I & II: Number of Participants Experiencing Clinical or Laboratory Adverse Experiences (AE) [Day 1 up until 30 days post study completion or early termination (up to approximately 506 days)]

   A laboratory AE is defined as any unfavorable & unintended change in the chemistry of the body temporally associated with the use of study product, whether or not considered related to the use of the product. A clinical AE is defined similarly but also includes changes in structure or function of the body.

2. Part I: Number of Participants Experiencing Dose Limiting Toxicity (DLT) [Day 1 to Day 28]

   A DLT was defined as any of the following (per Common Terminology Criteria for Adverse Events [CTCAE] version 3.0): Grade 3 (severe)-4 (life-threatening) neutropenia with fever ≥ 38.5ºC Grade 3-4 neutropenia with an infection requiring antibiotic or antifungal treatment Grade 4 neutropenia lasting at least 5 days Grade 4 thrombocytopenia Other Grade 4 hematologic toxicity, including a decrease in hemoglobin, only at the discretion of the principal investigator Grade 3 or 4 non-hematologic event, except which are manageable by supportive care or non-prohibited therapies

Secondary Outcome Measures

1. Part I: Total Drug Exposure (Area Under the Concentration Curve, AUC[0-24 Hours]) [Days 1 & 28 of Cycle 1]

   Blood samples taken as follows: Day 1 & Day 28 of Cycle 1: pre dose, and 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and 24 hours after dosing of vorinostat.

2. Part I: Maximum Drug Concentration (Cmax) [Days 1 & 28 of Cycle 1]

   Blood samples taken as follows: Day 1 & Day 28 of Cycle 1: pre dose, and 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and 24 hours after dosing of vorinostat.

3. Part I: Time at Which Cmax Occurs (Tmax) [Days 1 & 28 of Cycle 1]

   Blood samples taken as follows: Day 1 & Day 28 of Cycle 1: pre dose, and 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and 24 hours after dosing of vorinostat.

4. Part I: The Amount of Time it Takes for the Drug Concentration to Decrease by Half (T1/2) [Days 1 & 28 of Cycle 1]

   Blood samples taken as follows: Day 1 & Day 28 of Cycle 1: pre dose, and 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and 24 hours after dosing of vorinostat.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria (Parts I & II):

• Patients With CTCL Who Have Progressive, Persistent Or Recurrent Disease Subsequent To At Least One Prior Therapy

• Eastern Cooperative Oncology Group (ECOG) Performance Status Must Be 0-2

• Patients Have Adequate Bone Marrow, Liver Function And Renal Function

Exclusion Criteria (Parts I & II):

• Patients Had Prior Therapy Within 3 Weeks Before Registration, Or Have Not Recovered From Toxicities Of Prior Therapy

• Patients Have Uncontrolled Intercurrent Illness

• Pregnant Or Women Have A Will To Be Pregnant And Lactating Woman

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme Corp.

Investigators

• Study Director: Medical Monitor, Merck Sharp & Dohme Corp.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme Corp.
• ClinicalTrials.gov Identifier: NCT00771472
• Other Study ID Numbers: 0683-089; 2008_565
• First Posted: Oct 13, 2008
• Last Update Posted: Apr 21, 2015
• Last Verified: Apr 1, 2015

• Additional relevant MeSH terms: Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Cutaneous; Vorinostat

Study Results

Participant Flow

Arm/Group Title	Part I	Part II
Arm/Group Description	Vorinostat 400 mg oral, daily (QD). Treatment period was 28 days per cycle.	Vorinostat 400 mg oral, daily (QD). Treatment period was 28 days per cycle.
Period Title: Overall Study
STARTED	6	4
COMPLETED	0	0
NOT COMPLETED	6	4

Baseline Characteristics

Arm/Group Title	Vorinostat
Arm/Group Description	Parts I & II: vorinostat (400 mg) oral, daily (QD). Treatment period was 28 days per cycle.
Overall Participants	10
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.5 (12.0)
Sex: Female, Male (Count of Participants)
Female	2 20%
Male	8 80%
Region of Enrollment (participants) [Number]
Japan	10 100%

Outcome Measures

1. Primary Outcome

Title	Parts I & II: Number of Participants Experiencing Clinical or Laboratory Adverse Experiences (AE)
Description	A laboratory AE is defined as any unfavorable & unintended change in the chemistry of the body temporally associated with the use of study product, whether or not considered related to the use of the product. A clinical AE is defined similarly but also includes changes in structure or function of the body.
Time Frame	Day 1 up until 30 days post study completion or early termination (up to approximately 506 days)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vorinostat
Arm/Group Description	Parts I & II: vorinostat (400 mg) oral, daily (QD). Treatment period was 28 days per cycle.
Measure Participants	10
Clinical AEs	10 100%
Laboratory AEs	6 60%

2. Secondary Outcome

Title	Part I: Total Drug Exposure (Area Under the Concentration Curve, AUC[0-24 Hours])
Description	Blood samples taken as follows: Day 1 & Day 28 of Cycle 1: pre dose, and 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and 24 hours after dosing of vorinostat.
Time Frame	Days 1 & 28 of Cycle 1

Outcome Measure Data

Analysis Population Description

Number of participants with samples at the specified time point

Arm/Group Title	Vorinostat
Arm/Group Description	Part I: vorinostat (400 mg) oral, daily (QD). Treatment period was 28 days per cycle.
Measure Participants	6
Day 1 (n=6)	4.59 (2.34)
Day 28 (n=5)	5.59 (1.24)

3. Primary Outcome

Title	Part I: Number of Participants Experiencing Dose Limiting Toxicity (DLT)
Description	A DLT was defined as any of the following (per Common Terminology Criteria for Adverse Events [CTCAE] version 3.0): Grade 3 (severe)-4 (life-threatening) neutropenia with fever ≥ 38.5ºC Grade 3-4 neutropenia with an infection requiring antibiotic or antifungal treatment Grade 4 neutropenia lasting at least 5 days Grade 4 thrombocytopenia Other Grade 4 hematologic toxicity, including a decrease in hemoglobin, only at the discretion of the principal investigator Grade 3 or 4 non-hematologic event, except which are manageable by supportive care or non-prohibited therapies
Time Frame	Day 1 to Day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vorinostat
Arm/Group Description	Part I: vorinostat (400 mg) oral, daily (QD). Treatment period was 28 days per cycle.
Measure Participants	6
Number [participants]	1 10%

4. Secondary Outcome

Title	Part I: Maximum Drug Concentration (Cmax)
Description	Blood samples taken as follows: Day 1 & Day 28 of Cycle 1: pre dose, and 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and 24 hours after dosing of vorinostat.
Time Frame	Days 1 & 28 of Cycle 1

Outcome Measure Data

Analysis Population Description

Number of participants with samples at the specified time point

Arm/Group Title	Vorinostat
Arm/Group Description	Part I: vorinostat (400 mg) oral, daily (QD). Treatment period was 28 days per cycle.
Measure Participants	6
Day 1 (n=6)	0.83 (0.37)
Day 28 (n=5)	1.17 (0.37)

5. Secondary Outcome

Title	Part I: Time at Which Cmax Occurs (Tmax)
Description	Blood samples taken as follows: Day 1 & Day 28 of Cycle 1: pre dose, and 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and 24 hours after dosing of vorinostat.
Time Frame	Days 1 & 28 of Cycle 1

Outcome Measure Data

Analysis Population Description

Number of participants with samples at the specified time point

Arm/Group Title	Vorinostat
Arm/Group Description	Part I: vorinostat (400 mg) oral, daily (QD). Treatment period was 28 days per cycle.
Measure Participants	6
Day 1 (n=6)	2.91
Day 28 (n=5)	3.73

6. Secondary Outcome

Title	Part I: The Amount of Time it Takes for the Drug Concentration to Decrease by Half (T1/2)
Description	Blood samples taken as follows: Day 1 & Day 28 of Cycle 1: pre dose, and 0.25, 0.5, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 10, 12 and 24 hours after dosing of vorinostat.
Time Frame	Days 1 & 28 of Cycle 1

Outcome Measure Data

Analysis Population Description

Number of participants with samples at the specified time point

Arm/Group Title	Vorinostat
Arm/Group Description	Part I: vorinostat (400 mg) oral, daily (QD). Treatment period was 28 days per cycle.
Measure Participants	6
Day 1 (n=5)	1.94 (1.30)
Day 28 (n=4)	2.30 (1.10)

Adverse Events

Arm/Group Title	Vorinostat
Arm/Group Description	Parts I & II: vorinostat(400 mg) Oral, daily (QD). Treatment period was 28 days per cycle.
All Cause Mortality
	Vorinostat
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Vorinostat
	Affected / at Risk (%)	# Events
Total	3/10 (30%)
Gastrointestinal disorders
Nausea	1/10 (10%)	1
Vomiting	1/10 (10%)	1
Infections and infestations
Cellulitis streptococcal	1/10 (10%)	1
Infection	2/10 (20%)	2
Other (Not Including Serious) Adverse Events
	Vorinostat
	Affected / at Risk (%)	# Events
Total	10/10 (100%)
Blood and lymphatic system disorders
Anaemia	3/10 (30%)	3
Erythropenia	1/10 (10%)	1
Leukocytosis	1/10 (10%)	1
Leukopenia	3/10 (30%)	7
Lymphopenia	2/10 (20%)	3
Neutropenia	1/10 (10%)	2
Thrombocytopenia	8/10 (80%)	29
Cardiac disorders
Atrial fibrillation	1/10 (10%)	1
Eye disorders
Conjunctivitis	1/10 (10%)	1
Vitreous floaters	1/10 (10%)	1
Gastrointestinal disorders
Abdominal pain upper	2/10 (20%)	3
Cheilitis	2/10 (20%)	4
Constipation	3/10 (30%)	6
Diarrhoea	4/10 (40%)	5
Dry mouth	1/10 (10%)	1
Dyspepsia	1/10 (10%)	1
Nausea	6/10 (60%)	16
Vomiting	4/10 (40%)	7
General disorders
Chills	1/10 (10%)	2
Fatigue	4/10 (40%)	6
Malaise	5/10 (50%)	10
Oedema peripheral	2/10 (20%)	2
Pyrexia	4/10 (40%)	9
Swelling	1/10 (10%)	1
Hepatobiliary disorders
Cholecystitis acute	1/10 (10%)	1
Cholelithiasis	1/10 (10%)	1
Hepatic function abnormal	2/10 (20%)	3
Hyperbilirubinaemia	3/10 (30%)	14
Infections and infestations
Bacterial infection	1/10 (10%)	1
Body tinea	1/10 (10%)	1
Candidiasis	1/10 (10%)	1
Infection	1/10 (10%)	1
Keratitis herpetic	1/10 (10%)	1
Nasopharyngitis	1/10 (10%)	1
Oral candidiasis	1/10 (10%)	1
Viral infection	1/10 (10%)	1
Injury, poisoning and procedural complications
Contusion	1/10 (10%)	1
Investigations
Alanine aminotransferase increased	1/10 (10%)	3
Aspartate aminotransferase increased	2/10 (20%)	5
Blood alkaline phosphatase increased	1/10 (10%)	2
Blood cholinesterase increased	1/10 (10%)	1
Blood creatinine increased	2/10 (20%)	3
Blood fibrinogen increased	1/10 (10%)	1
Blood lactate dehydrogenase increased	1/10 (10%)	3
Blood urea increased	1/10 (10%)	1
C-reactive protein increased	1/10 (10%)	2
Fibrin D dimer increased	1/10 (10%)	2
Gamma-glutamyltransferase increased	1/10 (10%)	1
Haemoglobin decreased	1/10 (10%)	1
Lymphocyte count decreased	1/10 (10%)	1
Platelet count decreased	1/10 (10%)	2
Prothrombin time shortened	1/10 (10%)	1
Weight decreased	3/10 (30%)	3
Metabolism and nutrition disorders
Anorexia	6/10 (60%)	11
Dehydration	2/10 (20%)	2
Diabetes mellitus	1/10 (10%)	1
Hypercreatininaemia	3/10 (30%)	3
Hyperglycaemia	3/10 (30%)	7
Hyperkalaemia	1/10 (10%)	1
Hypermagnesaemia	4/10 (40%)	6
Hyperphosphataemia	2/10 (20%)	3
Hypertriglyceridaemia	4/10 (40%)	7
Hypoalbuminaemia	5/10 (50%)	5
Hypokalaemia	1/10 (10%)	1
Hyponatraemia	1/10 (10%)	1
Musculoskeletal and connective tissue disorders
Back pain	1/10 (10%)	1
Groin pain	1/10 (10%)	1
Hypercreatinaemia	2/10 (20%)	3
Muscle spasms	1/10 (10%)	2
Pain in jaw	1/10 (10%)	1
Nervous system disorders
Ageusia	1/10 (10%)	1
Dizziness postural	1/10 (10%)	1
Dysgeusia	4/10 (40%)	5
Headache	3/10 (30%)	5
Hypoaesthesia	1/10 (10%)	1
Lethargy	2/10 (20%)	2
Somnolence	1/10 (10%)	1
Psychiatric disorders
Insomnia	1/10 (10%)	1
Renal and urinary disorders
Dysuria	1/10 (10%)	1
Haemoglobinuria	2/10 (20%)	2
Proteinuria	4/10 (40%)	4
Renal impairment	2/10 (20%)	3
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	1/10 (10%)	2
Pleural effusion	1/10 (10%)	1
Skin and subcutaneous tissue disorders
Dermatitis contact	1/10 (10%)	1
Skin fissures	1/10 (10%)	1
Vascular disorders
Hypertension	2/10 (20%)	12
Hypotension	1/10 (10%)	1
Lymphoedema	1/10 (10%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication guidelines.