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Vatalanib in Treating Patients With Primary or Secondary Myelodysplastic Syndromes
This study is ongoing, but not recruiting participants.

First Received on November 4, 2003.   Last Updated on June 21, 2011   History of Changes
Sponsor: Cancer and Leukemia Group B
Collaborator: National Cancer Institute (NCI)
Information provided by: Cancer and Leukemia Group B
ClinicalTrials.gov Identifier: NCT00072475
  Purpose

RATIONALE: Vatalanib may be effective in preventing the development of leukemia in patients who have myelodysplastic syndromes.

PURPOSE: This phase II trial is studying vatalanib to see how well it works in treating patients with primary or secondary myelodysplastic syndromes.


Condition Intervention Phase
Leukemia
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
Drug: vatalanib
Phase II

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of an Oral VEGF Receptor Tyrosine Kinase Inhibitor (PTK787/ZK222584) (IND #66370, NSC #719335) in Myelodysplastic Syndrome (MDS)

Resource links provided by NLM:


Further study details as provided by Cancer and Leukemia Group B:

Primary Outcome Measures:
  • Hematologic Response rate [ Time Frame: 5 yrs ] [ Designated as safety issue: No ]
    measured by International Standardized Response Criteria for myelodysplastic syndromes (MDS)


Secondary Outcome Measures:
  • Safety [ Time Frame: Monthly ] [ Designated as safety issue: Yes ]
    Measured by Common Terminology Criteria for Adverse Events (CTCAE)

  • Duration of response [ Time Frame: 5 yrs ] [ Designated as safety issue: No ]
    Measured by International Standardized Response Criteria for MDS

  • Overall survival [ Time Frame: 5 yrs ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: 1 yr ] [ Designated as safety issue: No ]
    Measured by International Standardized Response Criteria for MDS


Enrollment: 155
Study Start Date: December 2003
Estimated Study Completion Date: December 2013
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vatalanib
Adult patients with MDS receive treatment with vatalanib
Drug: vatalanib
Pts registered before 1/15/05 1250 mg/day PO After 1/15/05: Start w/ 750 mg/day PO; escalate q 4 wks in absence of Grade 2 or > tox (1st increase=1000mg/day; 2nd increase 1250 mg/day)
Other Name: PTK787/ZK 222584

Detailed Description:

OBJECTIVES:

Primary

  • Determine the response rate, in terms of hematologic improvement and complete and partial remission, in patients with primary or secondary (therapy-related) myelodysplastic syndromes treated with vatalanib.
  • Determine the time to transformation to acute myeloid leukemia (at least 20% blasts) or death in patients treated with this drug.

Secondary

  • Determine the safety of this drug in these patients.
  • Determine the duration of response in patients treated with this drug.
  • Determine the cytogenetic response rate in patients treated with this drug.
  • Determine the overall and progression-free survival of patients treated with this drug.
  • Determine the incidence of infections requiring antibiotics or hospitalization or bleeding requiring red blood cell transfusions in patients treated with this drug.

OUTLINE: This is a multicenter study. Patients are stratified* according to risk group (low grade [refractory anemia with or without ringed sideroblasts, refractory anemia with excess blasts-1, refractory cytopenia with multilineage dysplasia with or without ringed sideroblasts, myelodysplastic syndromes-unclassified, or chronic myelomonocytic leukemia-1] vs high grade [refractory anemia with excess blasts-2 or chronic myelomonocytic leukemia-2]).

NOTE: *Stratification according to risk (low vs high) does not occur after 11/30/06.

Patients receive oral vatalanib once daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with a complete response (CR) receive 6 additional courses after documentation of a CR.

Patients are followed periodically for up to 5 years from study entry.

PROJECTED ACCRUAL: Approximately 144 patients will be accrued for this study within 2.5 years.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • Diagnosis of primary or secondary (therapy-related) myelodysplastic syndromes* (MDS), including the following cellular types:

    • Refractory anemia (RA)**
    • RA with excess blasts (RAEB)-1
    • RA with ringed sideroblasts**
    • Refractory cytopenia with multilineage dysplasia
    • Refractory cytopenia with multilineage dysplasia with ringed sideroblasts*
    • MDS-unclassified**
    • MDS associated with isolated del (5q)**
    • Chronic myelomonocytic leukemia (CMML)-1 NOTE: *High-risk MDS (i.e., RAEB-2 or CMML-2) is closed to accrual as of 11/30/06

NOTE: **Accompanied with at least 1 of the following laboratory values: hemoglobin less than 10 g/dL, platelet count less than 50,000/mm3, or absolute neutrophil count less than 1,000/mm3

  • No prior leukemia (i.e., 20% or greater blasts)
  • No prior primary or metastatic brain tumor or carcinomatous meningitis

PATIENT CHARACTERISTICS:

Age

  • 18 and over

Performance status

  • WHO 0-2

Life expectancy

  • Not specified

Hematopoietic

  • See Disease Characteristics

Hepatic

  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • AST no greater than 2.5 times ULN
  • APTT no greater than 1.5 times ULN
  • INR no greater than 1.5

Renal

  • Creatinine no greater than 1.5 times ULN
  • Urine protein negative by urinalysis

    • Protein 1+ by dipstick allowed provided total urine protein no greater than 500 mg AND creatinine clearance at least 50 mL/min by 24-hour urine collection

Cardiovascular

  • No significant cardiac or vascular events within the past 6 months, including any of the following:

    • Acute myocardial infarction
    • Unstable angina
    • Uncontrolled hypertension
    • Severe peripheral vascular disease (e.g., ischemic pain at rest or nonhealing ulcers or wounds)
    • New York Heart Association class II-IV congestive heart failure
    • Cardiac arrhythmia
    • Disseminated intravascular coagulation or other coagulopathies
    • Deep vein or arterial thrombosis
  • No history of congenital long QTc syndrome or elongated QTc (> 450 msec for males or 470 for females)

Pulmonary

  • No pulmonary embolism within the past 6 months

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective barrier contraception during and for at least 3 months after study participation
  • No need for full anticoagulation within the past 6 months
  • No significant hemorrhage (e.g., visceral, gastrointestinal, genitourinary, or gynecological) requiring red blood cell transfusion within the past month
  • No known cerebral aneurysms, other cerebrovascular malformations, or CNS bleeding
  • No unhealed fractures, wounds, or ulcers

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • More than 12 months since prior autologous stem cell or allogeneic transplantation
  • More than 6 months since prior antiangiogenic agents
  • More than 1 month since prior interferon for MDS
  • More than 1 month since prior hematopoietic growth factors for MDS
  • More than 1 month since prior epoetin alfa (EPO) for MDS
  • More than 1 month since prior thalidomide for MDS
  • More than 1 month since prior immunotherapy for MDS
  • No concurrent prophylactic growth factors or cytokines (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], EPO or EPO-derivatives, or interleukin-11)

Chemotherapy

  • No prior low-dose antimetabolites for MDS (e.g., hydroxyurea, azacitidine, or low-dose cytarabine)
  • More than 12 months since prior chemotherapy for another disease* NOTE: *Not MDS or leukemia

Endocrine therapy

  • More than 1 month since prior corticosteroids for MDS
  • More than 1 month since prior androgens for MDS

Radiotherapy

  • More than 12 months since prior radiotherapy for another disease* NOTE: *Not MDS or leukemia

Surgery

  • More than 1 month since prior surgery, including needle biopsy of visceral organs and recovered

    • Bone marrow biopsy allowed
  • More than 2 weeks since prior placement of a subcutaneous or tunneled venous access device (e.g., PortaCath or Hickman's catheter) and adequately healed

Other

  • No prior cytotoxic therapy for MDS
  • More than 1 month since prior administration of any of the following medications for MDS:

    • Danazol
    • Retinoids
    • Amifostine
    • Investigational agents
  • No concurrent administration of any of the following medications:

    • Warfarin
    • Heparin
    • Derivatives of heparin
    • Other anticoagulants
  • No concurrent grapefruit or grapefruit juice
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00072475

  Show 68 Study Locations
Sponsors and Collaborators
Cancer and Leukemia Group B
Investigators
Study Chair: Pankaj Gupta, MD Veterans Affairs Medical Center - Minneapolis
  More Information

Additional Information:
Publications:
Gupta P, Miller AA, Owzar K, et al.: Pharmacokinetics of an oral VEGF receptor tyrosine kinase inhibitor (PTK787/ZK222584) in patients with myelodysplastic syndrome (MDS): Cancer and Leukemia Group B study 10105. [Abstract] J Clin Oncol 24 (Suppl 18): A-6573, 355s, 2006.
Gupta P, Sanford BL, Yu D, et al.: A phase II study of an oral VEGF receptor tyrosine kinase inhibitor (PTK787/ZK222584) in patients with myelodysplastic syndrome (MDS): Cancer and Leukemia Group B study 10105. [Abstract] Blood 108 (11): A-2665, 2006.

Responsible Party: Monica M. Bertagnolli, Cancer and Leukemia Group B
ClinicalTrials.gov Identifier: NCT00072475     History of Changes
Other Study ID Numbers: CDR0000339810, U10CA031946, CALGB-10105
Study First Received: November 4, 2003
Last Updated: June 21, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Cancer and Leukemia Group B:
refractory anemia with excess blasts
refractory anemia with ringed sideroblasts
refractory cytopenia with multilineage dysplasia
chronic myelomonocytic leukemia
de novo myelodysplastic syndromes
secondary myelodysplastic syndromes
myelodysplastic/myeloproliferative neoplasm, unclassifiable
refractory anemia
previously treated myelodysplastic syndromes

Additional relevant MeSH terms:
Neoplasms
Leukemia
Myelodysplastic Syndromes
Preleukemia
Myeloproliferative Disorders
Myelodysplastic-Myeloproliferative Diseases
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Vatalanib
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 12, 2012