Trial Outcomes & Findings for PTK/ZK as Post Transplant Maintenance Therapy in Patients With Multiple Myeloma (NCT NCT00240162)
NCT ID: NCT00240162
Last Updated: 2014-09-17
Results Overview
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
21 participants
Primary outcome timeframe
Day 90
Results posted on
2014-09-17
Participant Flow
The study opened to participant enrollment on 09/21/2005 and closed to participant enrollment on 06/17/2008.
Participant milestones
| Measure |
PTK787/ZK 222584
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 Study
STARTED
|
21
|
|
Overall Study
COMPLETED
|
21
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
PTK/ZK as Post Transplant Maintenance Therapy in Patients With Multiple Myeloma
Baseline characteristics by cohort
| Measure |
PTK787/ZK 222584
n=21 Participants
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.
|
|---|---|
|
Age, Continuous
|
57 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
14 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
21 participants
n=5 Participants
|
|
Durie-Salmon stage at study entry
Stage IA
|
7 participants
n=5 Participants
|
|
Durie-Salmon stage at study entry
Stage IIA
|
7 participants
n=5 Participants
|
|
Durie-Salmon stage at study entry
Stage IIIA
|
7 participants
n=5 Participants
|
|
International Staging System (ISS) at study entry
Stage I
|
17 participants
n=5 Participants
|
|
International Staging System (ISS) at study entry
Stage II
|
3 participants
n=5 Participants
|
|
International Staging System (ISS) at study entry
Stage III
|
1 participants
n=5 Participants
|
|
Beta-2 Microglobulin at study entry
|
2.3 mg/L
n=5 Participants
|
|
Paraprotein at study entry
IgG
|
18 participants
n=5 Participants
|
|
Paraprotein at study entry
IgA
|
3 participants
n=5 Participants
|
|
Serum M-spike at study entry
|
0.5 g/dL
n=5 Participants
|
|
Bone marrow aspirate plasma
|
5 percentage of cells at study entry
n=5 Participants
|
|
Conventional cytogenetics
Normal karyotype
|
8 participants
n=5 Participants
|
|
Conventional cytogenetics
Monosomy 13
|
1 participants
n=5 Participants
|
|
Conventional cytogenetics
Hypodiploid karyotype with t(11;14)
|
1 participants
n=5 Participants
|
|
Conventional cytogenetics
Monosomy 13 and t(4:14)
|
2 participants
n=5 Participants
|
|
Conventional cytogenetics
Others
|
8 participants
n=5 Participants
|
|
Conventional cytogenetics
No available cytogenetics
|
1 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 90Population: Participants were evaluable for response if they completed 3 cycles of treatment. 10 out of 21 participants completed 3 cycles of treatment.
Outcome measures
| Measure |
PTK787/ZK 222584
n=10 Participants
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.
|
|---|---|
|
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
Partial response
|
1 participants
|
|
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
No response
|
9 participants
|
|
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
Complete response
|
0 participants
|
SECONDARY outcome
Timeframe: Until the patient progresses or expires (up to 457 days)Population: Participants were evaluable for time to progression if they completed 3 cycles of treatment. 10 out of 21 participants completed 3 cycles of treatment.
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
Outcome measures
| Measure |
PTK787/ZK 222584
n=10 Participants
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.
|
|---|---|
|
Time to Progression
|
149 days
Interval 28.0 to 457.0
|
SECONDARY outcome
Timeframe: 30 days after treatment ends [median of 15 cycles (11-32)]Population: Only 13 out of the 21 participants experienced a grade 3 or 4 adverse event.
Number of Grade 3/4 adverse events per the National Cancer Institute (NCI) Common Toxicity Criteria v 3.0.
Outcome measures
| Measure |
PTK787/ZK 222584
n=21 Participants
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.
|
|---|---|
|
Safety and Tolerability of PTK787/ZK 222584
Gastrointestinal toxicity
|
8 adverse events
|
|
Safety and Tolerability of PTK787/ZK 222584
Neurologic toxicity
|
5 adverse events
|
|
Safety and Tolerability of PTK787/ZK 222584
Cardiac toxicity
|
4 adverse events
|
|
Safety and Tolerability of PTK787/ZK 222584
Hematological toxicity
|
3 adverse events
|
SECONDARY outcome
Timeframe: Until the patient expiresPopulation: This secondary outcome was not analyzed.
Outcome measures
Outcome data not reported
Adverse Events
PTK787/ZK 222584
Serious events: 3 serious events
Other events: 21 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
PTK787/ZK 222584
n=21 participants at risk
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.
|
|---|---|
|
Cardiac disorders
Hypertension
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Infections and infestations
Infection without neutropenia (pneumonia)
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Cardiac disorders
Hypotension
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
Other adverse events
| Measure |
PTK787/ZK 222584
n=21 participants at risk
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.
|
|---|---|
|
Gastrointestinal disorders
Abdominal pain
|
9.5%
2/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Investigations
Alkaline phosphatase
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
9.5%
2/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Metabolism and nutrition disorders
Anorexia
|
47.6%
10/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
14.3%
3/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
9.5%
2/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Gastrointestinal disorders
Belching
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
General disorders
Bilateral lower extremity edema
|
9.5%
2/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Nervous system disorders
CNS cerebrovascular ischemia
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Cardiac disorders
Cardiac troponin
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Musculoskeletal and connective tissue disorders
Chest pain
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Congestion
|
9.5%
2/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Gastrointestinal disorders
Constipation
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Cardiac disorders
Coronary artery disease
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
33.3%
7/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
General disorders
Diaphoresis
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Gastrointestinal disorders
Diarrhea
|
23.8%
5/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Gastrointestinal disorders
Distension
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Nervous system disorders
Dizziness
|
19.0%
4/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Injury, poisoning and procedural complications
Dog bite
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Gastrointestinal disorders
Dysgeusia
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Gastrointestinal disorders
Dyspepsia/heartburn
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Gastrointestinal disorders
Dysphagia
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
33.3%
7/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Gastrointestinal disorders
Early satiety
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Investigations
Elevated creatinine
|
19.0%
4/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Skin and subcutaneous tissue disorders
Erythema
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Vascular disorders
Facial flushing
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
General disorders
Fatigue
|
57.1%
12/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
General disorders
Fever - no infection
|
14.3%
3/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Gastrointestinal disorders
Flatulence
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Gastrointestinal disorders
GERD
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Gastrointestinal disorders
Gastritis
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
General disorders
Generalized pain
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Nervous system disorders
Headache
|
33.3%
7/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Blood and lymphatic system disorders
Hemoglobin
|
28.6%
6/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Musculoskeletal and connective tissue disorders
Hiatal hernia
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Musculoskeletal and connective tissue disorders
Hip pain
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Investigations
Hypercalcemia
|
19.0%
4/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Investigations
Hypercholesterolemia
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Investigations
Hyperkalemia
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Investigations
Hypermagnesemia
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Investigations
Hypernatremia
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Cardiac disorders
Hypertension
|
33.3%
7/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Investigations
Hypertriglyceridemia
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Investigations
Hypoalbuminemia
|
9.5%
2/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Investigations
Hypocalcemia
|
9.5%
2/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Investigations
Hyponatremia
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Skin and subcutaneous tissue disorders
Hypopigmentation
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Infections and infestations
Infection with unknown ANC
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Infections and infestations
Infection without neutropenia
|
28.6%
6/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Psychiatric disorders
Insomnia
|
9.5%
2/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Cardiac disorders
Left ventricular dysfunction
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Investigations
Leukocytes (WBC)
|
23.8%
5/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Musculoskeletal and connective tissue disorders
Lower extremity pain
|
9.5%
2/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Investigations
Lymphopenia
|
28.6%
6/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Nervous system disorders
Mental haziness
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Psychiatric disorders
Mood alteration - anxiety
|
9.5%
2/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Psychiatric disorders
Mood alteration - depression
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Nervous system disorders
Motor neuropathy
|
14.3%
3/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
19.0%
4/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Gastrointestinal disorders
Nausea
|
66.7%
14/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Investigations
Neutrophils (ANC)
|
23.8%
5/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Gastrointestinal disorders
Oral thrush
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Investigations
Platelets
|
28.6%
6/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Nervous system disorders
Post-herpetic neuralgia
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Cardiac disorders
Prolonged QTC
|
9.5%
2/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Renal and urinary disorders
Proteinuria
|
14.3%
3/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Skin and subcutaneous tissue disorders
Rash/desquamation
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
General disorders
Rigors
|
9.5%
2/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Investigations
SGOT (AST)
|
23.8%
5/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Investigations
SGPT (ALT)
|
33.3%
7/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Nervous system disorders
Sensory neuropathy
|
19.0%
4/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Cardiac disorders
Sinus tachycardia
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Musculoskeletal and connective tissue disorders
Substernal (xiphoid) pain
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Ear and labyrinth disorders
Tinnitus
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Renal and urinary disorders
Urinary frequency/urgency
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Gastrointestinal disorders
Vomiting
|
42.9%
9/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Musculoskeletal and connective tissue disorders
Weakness
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
|
Gastrointestinal disorders
Weight loss
|
4.8%
1/21 • Adverse events were collected from the start of treatment up through 30 days following the end of treatment.
|
Additional Information
Ravi Vij, M.D.
Washington University School of Medicine
Phone: 314-454-8304
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place