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

This study has been terminated.
(investigator letter from drug manufacturer stating animal studies showed increased risk of cancer which was an unknown adverse event)
Sponsor:
Information provided by (Responsible Party):
Washington University School of Medicine
ClinicalTrials.gov Identifier:
NCT00240162
First received: October 13, 2005
Last updated: September 5, 2014
Last verified: September 2014
  Purpose

The purpose of this study it to evaluate the efficacy of PTK787/ZK 222584, in inducing at least a 50% reduction in paraprotein in patients with multiple myeloma whose paraprotein levels are < 5 g/dL following high dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT).


Condition Intervention Phase
Multiple Myeloma
Drug: PTK787/ZK 222584
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of PTK787/ZK 222584, a Novel, Oral Angiogenesis Inhibitor as Post Transplant Maintenance Therapy in Patients With Multiple Myeloma Following High Dose Chemotherapy and Autologous Stem Cell Transplant

Resource links provided by NLM:


Further study details as provided by Washington University School of Medicine:

Primary Outcome Measures:
  • 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 [ Time Frame: Day 90 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to Progression [ Time Frame: Until the patient progresses or expires (up to 457 days) ] [ Designated as safety issue: No ]

    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

  • Safety and Tolerability of PTK787/ZK 222584 [ Time Frame: 30 days after treatment ends [median of 15 cycles (11-32)] ] [ Designated as safety issue: Yes ]
    Number of Grade 3/4 adverse events per the National Cancer Institute (NCI) Common Toxicity Criteria v 3.0.

  • Disease Free Survival [ Time Frame: Until the patient expires ] [ Designated as safety issue: No ]

Enrollment: 21
Study Start Date: September 2005
Study Completion Date: December 2008
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: PTK787/ZK 222584
Other Name: N/Bemzoylstaurosporine

Detailed Description:

To evaluate the efficacy of PTK787/ZK 222584, in inducing at least a 50% reduction in paraprotein in patients with multiple myeloma whose paraprotein levels are < 5 g/dL following high dose chemotherapy (HDCT) and Autologous Stem Cell Transplantation (ASCT).

To assess the time to progression and disease free survival of patients treated with PTK787/ZK 222584.

To assess the safety and tolerability of PTK787/ZK 222584 in multiple myeloma patients following ASCT.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients eligible for this trial are those diagnosed with multiple myeloma by standard criteria and treated with HDCT and ASCT on protocols at Washington University School of Medicine. Following HDCT and ASCT patients must have:

    1. M-component (IgG or IgA) with persistent measurable paraprotein, or >=2 g monoclonal protein in 24 hr urine specimen or patients with an abnormal serum kappa/lambda ratio and a level of kappa or lambda light chain > 10 mg/dl.
    2. >=90 days and <= 120 days post transplant
    3. Laboratory values less than or equal to 2 weeks prior to initiation of treatment:

      • Absolute neutrophil count (ANC) greater than or equal 1.5 x 10^9/L
      • Platelets (PLT) greater than or equal to 100 x 10^9/L
      • Hemoglobin (Hgb) greater than or equal to 9 g/dL
      • Serum creatinine less than or equal to 1.5 upper limit of normal (ULN)
      • Serum bilirubin less than or equal to 1.5 ULN
      • Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) less than or equal to 3.0 x ULN
      • Negative for proteinuria based on dip stick reading OR, if documentation of +1 result for protein on dip stick reading, then total urinary albumin ≤ 500 mg and measured creatinine clearance (CrCl) greater than or equal to 50 mL/min from a 24-hour urine collection
    4. A negative pregnancy test 48 hours prior to study treatment and must not be lactating if they are females of childbearing age.
    5. Ability to understand and the willingness to sign a written informed consent document in accordance with the guidelines of the Washington University Human Studies Committee.
    6. Age greater than or equal to 18 years old.
    7. ECOG performance status less than or equal to 2.

Exclusion Criteria:

  1. Receiving any other investigational agents.
  2. Receiving concurrent steroids with a dose equivalent of prednisone of >= 150 mg/month.
  3. Female patients who are pregnant or breast feeding, or adults of reproductive potential not employing an effective method of birth control. Barrier contraceptives must be used throughout the trial in both sexes. Oral, implantable, or injectable contraceptives may be affected by cytochrome P450 interactions, and are therefore not considered effective for this study.
  4. Biopsy proven amyloidosis.
  5. Patients with a history of another primary malignancy within less than or equal to 5 years, with the exception of inactive basal or squamous cell carcinoma of the skin.
  6. Prior chemotherapy less than or equal to 3 weeks prior to registration and/or randomization. Patients must have recovered from all therapy-related toxicities.
  7. Prior biologic or immunotherapy less than or equal to 2 weeks prior to registration and/or randomization. Patients must have recovered from all therapy-related toxicities.
  8. Prior full field radiotherapy less than or equal to 4 weeks or limited field radiotherapy less than or equal to 2 weeks prior to randomization. Patients must have recovered from all therapy-related toxicities.
  9. Pleural effusion or ascites that cause respiratory compromise (greater than or equal to CTC grade 2 dyspnea).
  10. Major surgery (i.e. laparotomy) less than or equal to 4 weeks prior to randomization. Minor surgery less than or equal to 2 weeks prior to randomization. Insertion of a vascular access device is not considered major or minor surgery in this regard. Patients must have recovered from all surgery-related toxicities.
  11. Patients who have received investigational drugs less than or equal to 4 weeks prior to registration and/or randomization.
  12. Prior therapy with anti-vascular endothelial growth factor (VEGF) agents.
  13. Any of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study:

    • Uncontrolled high blood pressure, history of labile hypertension, or history of poor compliance with an antihypertensive regimen
    • Unstable angina pectoris
    • Symptomatic congestive heart failure
    • Myocardial infarction less than or equal to 6 months prior to registration and/or randomization
    • Serious uncontrolled cardiac arrhythmia
    • QTc interval > 450 milliseconds in males or > 470 milliseconds in females Uncontrolled diabetes
    • Active or uncontrolled infection
    • Interstitial pneumonia or extensive and symptomatic interstitial fibrosis of the lung
  14. Acute or chronic liver disease (e.g. hepatitis, cirrhosis).
  15. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PTK787/ZK 222584 (i.e., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, bowel obstruction, or inability to swallow the tablets).
  16. Patients with confirmed diagnosis of human immunodeficiency virus (HIV) infection are excluded at the investigator's discretion if he/she feels that: a potential drug interaction between PTK787/ZK 222584 and any of the patient's anti-HIV medications could influence the efficacy of the anti-HIV medication, or it may place the patient at risk due to the pharmacologic activity of PTK787/ZK 222584.
  17. Patients who are taking therapeutic warfarin sodium (Coumadin) or similar oral anticoagulants that are metabolized by the cytochrome P450 system. Heparin is allowed.
  18. Patients unwilling to or unable to comply with the protocol.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00240162

Locations
United States, Missouri
Washington University School of Medicine
St. Louis, Missouri, United States, 63110
Sponsors and Collaborators
Washington University School of Medicine
Investigators
Principal Investigator: Ravi Vij, M.D. Washington University School of Medicine
  More Information

Additional Information:
No publications provided

Responsible Party: Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT00240162     History of Changes
Other Study ID Numbers: 05-0639, IND#: 72,721
Study First Received: October 13, 2005
Results First Received: August 22, 2014
Last Updated: September 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Washington University School of Medicine:
Myeloma
PTK

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Vatalanib
Angiogenesis Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014