PTK/ZK as Post Transplant Maintenance Therapy in Patients With Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: PTK787/ZK 222584
Intervention MeSH terms: Vatalanib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Myeloma; PTK

Summary:

      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).
    

Eligibility 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.