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PTK/ZK as Post Transplant Maintenance Therapy in Patients With Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00240162
Recruitment Status : Terminated (investigator letter from drug manufacturer stating animal studies showed increased risk of cancer which was an unknown adverse event)
First Posted : October 17, 2005
Results First Posted : September 4, 2014
Last Update Posted : September 17, 2014
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Myeloma
Intervention Drug: PTK787/ZK 222584
Enrollment 21
Recruitment Details The study opened to participant enrollment on 09/21/2005 and closed to participant enrollment on 06/17/2008.
Pre-assignment Details  
Arm/Group Title PTK787/ZK 222584
Hide Arm/Group Description Initially patients will receive a dose of 500mg (2, 250mg tablets) in the morning and 250mg (1, 250mg tablet) in the afternoon for 2 weeks (cycle 1, days 1-14), then 500mg (2, 250mg tablets) bid for 2 weeks (cycle 1, days 15-28) and finally 750mg (3, 250mg tablets) in the morning and 500mg (2, 250mg tablets) in the afternoon for the remainder of treatment duration (cycle 2, day 1 and onwards). Each 28 days of drug administration will constitute one cycle of therapy.
Period Title: Overall Study
Started 21
Completed 21
Not Completed 0
Arm/Group Title PTK787/ZK 222584
Hide Arm/Group Description Initially patients will receive a dose of 500mg (2, 250mg tablets) in the morning and 250mg (1, 250mg tablet) in the afternoon for 2 weeks (cycle 1, days 1-14), then 500mg (2, 250mg tablets) bid for 2 weeks (cycle 1, days 15-28) and finally 750mg (3, 250mg tablets) in the morning and 500mg (2, 250mg tablets) in the afternoon for the remainder of treatment duration (cycle 2, day 1 and onwards). Each 28 days of drug administration will constitute one cycle of therapy.
Overall Number of Baseline Participants 21
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 21 participants
57
(38 to 76)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants
Female
7
  33.3%
Male
14
  66.7%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 21 participants
21
Durie-Salmon stage at study entry   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 21 participants
Stage IA 7
Stage IIA 7
Stage IIIA 7
[1]
Measure Description:
  • Stage I:Hemoglobin (hgb) level >10.5 g/dL & calcium level is normal or ≤12 mg/dL & Low M-protein levels (IgG level is <5 g/dL; IgA level <3 g/dL) & Urine light chains <4 g per 24 hours, & Bone X-ray normal bone structure or a solitary bone plasmacytoma
  • Stage IIA:Levels of hgb, calcium, M-protein and Bence Jones protein fall somewhere between stages I and III & No kidney failure (creatinine ≤2 mg/dL)
  • Stage III: High M protein (IgG is>7 g/dL; IgA is >5g/dL) & Urine light chains >12 g per 24 hours & hgb <8.5 g/dL & calcium >2 m/dL) & X-ray studies of bone >3 lytic bone lesions
International Staging System (ISS) at study entry   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 21 participants
Stage I 17
Stage II 3
Stage III 1
[1]
Measure Description:
  • Stage I:Beta 2-microglobulin level <3.5 mg/L & Albumin level ≥3.5 g/dL
  • Stage II Beta 2-microglobulin level <3.5 g/L & Albumin level <3.5 g/dL OR Beta 2-microglobulin level is 3.5 to 5.5 mg/L
  • Stage III Beta 2-microglobulin level is ≥5.5 mg/L
Beta-2 Microglobulin at study entry  
Median (Full Range)
Unit of measure:  mg/L
Number Analyzed 21 participants
2.3
(1.2 to 5.65)
Paraprotein at study entry  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 21 participants
IgG 18
IgA 3
Serum M-spike at study entry  
Median (Full Range)
Unit of measure:  g/dL
Number Analyzed 21 participants
0.5
(0 to 2.4)
Bone marrow aspirate plasma  
Median (Full Range)
Unit of measure:  Percentage of cells at study entry
Number Analyzed 21 participants
5
(0 to 15)
Conventional cytogenetics  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 21 participants
Normal karyotype 8
Monosomy 13 1
Hypodiploid karyotype with t(11;14) 1
Monosomy 13 and t(4:14) 2
Others 8
No available cytogenetics 1
1.Primary Outcome
Title Detectable Paraprotein Level (IgG or IgA)at ≤5 g/dL Who Show a 50% Reduction (Complete Response + Partial Response) in Their Paraprotein After Starting Treatment With the Study Drug
Hide Description [Not Specified]
Time Frame Day 90
Hide Outcome Measure Data
Hide Analysis Population Description
Participants were evaluable for response if they completed 3 cycles of treatment. 10 out of 21 participants completed 3 cycles of treatment.
Arm/Group Title PTK787/ZK 222584
Hide Arm/Group Description:
Initially patients will receive a dose of 500mg (2, 250mg tablets) in the morning and 250mg (1, 250mg tablet) in the afternoon for 2 weeks (cycle 1, days 1-14), then 500mg (2, 250mg tablets) bid for 2 weeks (cycle 1, days 15-28) and finally 750mg (3, 250mg tablets) in the morning and 500mg (2, 250mg tablets) in the afternoon for the remainder of treatment duration (cycle 2, day 1 and onwards). Each 28 days of drug administration will constitute one cycle of therapy.
Overall Number of Participants Analyzed 10
Measure Type: Number
Unit of Measure: participants
Complete response 0
Partial response 1
No response 9
2.Secondary Outcome
Title Time to Progression
Hide Description

Time to progression is from the start of treatment until the first date that criteria for progressive disease (PD) are met.

  • 25% increase in the level of the serum monoclonal paraprotein, which must also be an absolute increase of at least 0.5 g/dL and confirmed by at lease 1 repeated investigation.
  • 25% increase in the 24 hr urinary light chain excretion, which must also be an absolute increase of at least 200 mg/ 24 hr and confirmed by at least 1 repeated investigation.
  • 35% increase in plasma cells in a bone marrow aspirate or on trephine biopsy, which must also be an absolute increase of at least 10%.

    • Increase in the size of existing bone lesions or soft tissue plasmacytomas
    • New lytic bone lesions or soft tissue plasmacytomas or definite increase in the size of residual bone lesions (development of a compression fracture does not exclude continued response and may not indicate progression).
    • Hypercalcemia - corrected serum calcium > 11.5 mg/dL
Time Frame Until the patient progresses or expires (up to 457 days)
Hide Outcome Measure Data
Hide Analysis Population Description
Participants were evaluable for time to progression if they completed 3 cycles of treatment. 10 out of 21 participants completed 3 cycles of treatment.
Arm/Group Title PTK787/ZK 222584
Hide Arm/Group Description:
Initially patients will receive a dose of 500mg (2, 250mg tablets) in the morning and 250mg (1, 250mg tablet) in the afternoon for 2 weeks (cycle 1, days 1-14), then 500mg (2, 250mg tablets) bid for 2 weeks (cycle 1, days 15-28) and finally 750mg (3, 250mg tablets) in the morning and 500mg (2, 250mg tablets) in the afternoon for the remainder of treatment duration (cycle 2, day 1 and onwards). Each 28 days of drug administration will constitute one cycle of therapy.
Overall Number of Participants Analyzed 10
Median (Full Range)
Unit of Measure: days
149
(28 to 457)
3.Secondary Outcome
Title Safety and Tolerability of PTK787/ZK 222584
Hide Description Number of Grade 3/4 adverse events per the National Cancer Institute (NCI) Common Toxicity Criteria v 3.0.
Time Frame 30 days after treatment ends [median of 15 cycles (11-32)]
Hide Outcome Measure Data
Hide Analysis Population Description
Only 13 out of the 21 participants experienced a grade 3 or 4 adverse event.
Arm/Group Title PTK787/ZK 222584
Hide Arm/Group Description:
Initially patients will receive a dose of 500mg (2, 250mg tablets) in the morning and 250mg (1, 250mg tablet) in the afternoon for 2 weeks (cycle 1, days 1-14), then 500mg (2, 250mg tablets) bid for 2 weeks (cycle 1, days 15-28) and finally 750mg (3, 250mg tablets) in the morning and 500mg (2, 250mg tablets) in the afternoon for the remainder of treatment duration (cycle 2, day 1 and onwards). Each 28 days of drug administration will constitute one cycle of therapy.
Overall Number of Participants Analyzed 21
Measure Type: Number
Unit of Measure: adverse events
Gastrointestinal toxicity 8
Neurologic toxicity 5
Cardiac toxicity 4
Hematological toxicity 3
4.Secondary Outcome
Title Disease Free Survival
Hide Description [Not Specified]
Time Frame Until the patient expires
Hide Outcome Measure Data
Hide Analysis Population Description
This secondary outcome was not analyzed.
Arm/Group Title PTK787/ZK 222584
Hide Arm/Group Description:
Initially patients will receive a dose of 500mg (2, 250mg tablets) in the morning and 250mg (1, 250mg tablet) in the afternoon for 2 weeks (cycle 1, days 1-14), then 500mg (2, 250mg tablets) bid for 2 weeks (cycle 1, days 15-28) and finally 750mg (3, 250mg tablets) in the morning and 500mg (2, 250mg tablets) in the afternoon for the remainder of treatment duration (cycle 2, day 1 and onwards). Each 28 days of drug administration will constitute one cycle of therapy.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title PTK787/ZK 222584
Hide Arm/Group Description Initially patients will receive a dose of 500mg (2, 250mg tablets) in the morning and 250mg (1, 250mg tablet) in the afternoon for 2 weeks (cycle 1, days 1-14), then 500mg (2, 250mg tablets) bid for 2 weeks (cycle 1, days 15-28) and finally 750mg (3, 250mg tablets) in the morning and 500mg (2, 250mg tablets) in the afternoon for the remainder of treatment duration (cycle 2, day 1 and onwards). Each 28 days of drug administration will constitute one cycle of therapy.
All-Cause Mortality
PTK787/ZK 222584
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
PTK787/ZK 222584
Affected / at Risk (%)
Total   3/21 (14.29%) 
Cardiac disorders   
Hypertension  1  1/21 (4.76%) 
Hypotension  1  1/21 (4.76%) 
Infections and infestations   
Infection without neutropenia (pneumonia)  1  1/21 (4.76%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
PTK787/ZK 222584
Affected / at Risk (%)
Total   21/21 (100.00%) 
Blood and lymphatic system disorders   
Hemoglobin  1  6/21 (28.57%) 
Cardiac disorders   
Cardiac troponin  1  1/21 (4.76%) 
Coronary artery disease  1  1/21 (4.76%) 
Hypertension  1  7/21 (33.33%) 
Left ventricular dysfunction  1  1/21 (4.76%) 
Prolonged QTC  1  2/21 (9.52%) 
Sinus tachycardia  1  1/21 (4.76%) 
Ear and labyrinth disorders   
Tinnitus  1  1/21 (4.76%) 
Gastrointestinal disorders   
Abdominal pain  1  2/21 (9.52%) 
Belching  1  1/21 (4.76%) 
Constipation  1  1/21 (4.76%) 
Diarrhea  1  5/21 (23.81%) 
Distension  1  1/21 (4.76%) 
Dysgeusia  1  1/21 (4.76%) 
Dyspepsia/heartburn  1  1/21 (4.76%) 
Dysphagia  1  1/21 (4.76%) 
Early satiety  1  1/21 (4.76%) 
Flatulence  1  1/21 (4.76%) 
GERD  1  1/21 (4.76%) 
Gastritis  1  1/21 (4.76%) 
Nausea  1  14/21 (66.67%) 
Oral thrush  1  1/21 (4.76%) 
Vomiting  1  9/21 (42.86%) 
Weight loss  1  1/21 (4.76%) 
General disorders   
Bilateral lower extremity edema  1  2/21 (9.52%) 
Diaphoresis  1  1/21 (4.76%) 
Fatigue  1  12/21 (57.14%) 
Fever - no infection  1  3/21 (14.29%) 
Generalized pain  1  1/21 (4.76%) 
Rigors  1  2/21 (9.52%) 
Infections and infestations   
Infection with unknown ANC  1  1/21 (4.76%) 
Infection without neutropenia  1  6/21 (28.57%) 
Injury, poisoning and procedural complications   
Dog bite  1  1/21 (4.76%) 
Investigations   
Alkaline phosphatase  1  1/21 (4.76%) 
Elevated creatinine  1  4/21 (19.05%) 
Hypercalcemia  1  4/21 (19.05%) 
Hypercholesterolemia  1  1/21 (4.76%) 
Hyperkalemia  1  1/21 (4.76%) 
Hypermagnesemia  1  1/21 (4.76%) 
Hypernatremia  1  1/21 (4.76%) 
Hypertriglyceridemia  1  1/21 (4.76%) 
Hypoalbuminemia  1  2/21 (9.52%) 
Hypocalcemia  1  2/21 (9.52%) 
Hyponatremia  1  1/21 (4.76%) 
Leukocytes (WBC)  1  5/21 (23.81%) 
Lymphopenia  1  6/21 (28.57%) 
Neutrophils (ANC)  1  5/21 (23.81%) 
Platelets  1  6/21 (28.57%) 
SGOT (AST)  1  5/21 (23.81%) 
SGPT (ALT)  1  7/21 (33.33%) 
Metabolism and nutrition disorders   
Anorexia  1  10/21 (47.62%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  3/21 (14.29%) 
Back pain  1  2/21 (9.52%) 
Bone pain  1  1/21 (4.76%) 
Chest pain  1  1/21 (4.76%) 
Hiatal hernia  1  1/21 (4.76%) 
Hip pain  1  1/21 (4.76%) 
Lower extremity pain  1  2/21 (9.52%) 
Myalgia  1  4/21 (19.05%) 
Substernal (xiphoid) pain  1  1/21 (4.76%) 
Weakness  1  1/21 (4.76%) 
Nervous system disorders   
CNS cerebrovascular ischemia  1  1/21 (4.76%) 
Dizziness  1  4/21 (19.05%) 
Headache  1  7/21 (33.33%) 
Mental haziness  1  1/21 (4.76%) 
Motor neuropathy  1  3/21 (14.29%) 
Post-herpetic neuralgia  1  1/21 (4.76%) 
Sensory neuropathy  1  4/21 (19.05%) 
Psychiatric disorders   
Insomnia  1  2/21 (9.52%) 
Mood alteration - anxiety  1  2/21 (9.52%) 
Mood alteration - depression  1  1/21 (4.76%) 
Renal and urinary disorders   
Proteinuria  1  3/21 (14.29%) 
Urinary frequency/urgency  1  1/21 (4.76%) 
Respiratory, thoracic and mediastinal disorders   
Allergic rhinitis  1  2/21 (9.52%) 
Congestion  1  2/21 (9.52%) 
Cough  1  7/21 (33.33%) 
Dyspnea  1  7/21 (33.33%) 
Skin and subcutaneous tissue disorders   
Erythema  1  1/21 (4.76%) 
Hypopigmentation  1  1/21 (4.76%) 
Rash/desquamation  1  1/21 (4.76%) 
Vascular disorders   
Facial flushing  1  1/21 (4.76%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
In November 2008, it was reported that the drug might have carcinogenic potential in animal models. At that time, the remaining three patients were taken off study.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Ravi Vij, M.D.
Organization: Washington University School of Medicine
Phone: 314-454-8304
EMail: rvij@dom.wustl.edu
Layout table for additonal information
Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00240162    
Other Study ID Numbers: 05-0639
IND#: 72,721
First Submitted: October 13, 2005
First Posted: October 17, 2005
Results First Submitted: August 22, 2014
Results First Posted: September 4, 2014
Last Update Posted: September 17, 2014