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Vatalanib in Treating Patients With Primary or Secondary Myelodysplastic Syndromes

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: NCT00072475
Recruitment Status : Completed
First Posted : November 6, 2003
Results First Posted : June 24, 2014
Last Update Posted : August 1, 2016
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology

Tracking Information
First Submitted Date  ICMJE November 4, 2003
First Posted Date  ICMJE November 6, 2003
Results First Submitted Date  ICMJE May 22, 2014
Results First Posted Date  ICMJE June 24, 2014
Last Update Posted Date August 1, 2016
Study Start Date  ICMJE December 2003
Actual Primary Completion Date November 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 22, 2014)
  • Number of Participants With Response [ Time Frame: Duration of study (up to 5 years) ]
    Response was measured by International Standardized Response Criteria for MDS
    • Complete Response: Bone marrow showing < 5% myeloblasts with normal maturation of all cell lines; Hgb > 11 g/dL (untransfused), ANC ≥1.5 K/L, PLT ≥ 100 K/L, No blasts, no dysplasia
    • Partial remission: All of the CR criteria (if abnormal at baseline), except BM evaluation. Blasts decreased by ≥ 50% over baseline. Cellularity and morphology are not relevant.
    Hematologic improvement:
    • Erythroid (HI-E): For participants with baseline HGB < 11g/dL, Major: > 2g/dL increase, transfusion independence. Minor: 1-2g/dL increase, ≥ 50% decrease in transfusion requirements
    • Platelet (HI-P): For participants with baseline PLT < 100 K/L: Major: absolute increase of > 30 K/L, transfusion independence. Minor: ≥ 50% increase (net increase of >10 K/L)
    • Neutrophil (HI-N): For participants with baseline ANC < 1.5 K/L, Major: > 100% increase (net increase > 0.5 K/L). Minor: > 100% increase (absolute increase < 0.5 K/L)
  • Time to Transformation to AML [ Time Frame: Duration of study (up to 5 years) ]
    Time to transformation to AML is defined as the time from registration to the transformation of MDS to AML or death of any cause. Participants not meeting these criteria were censored at the date of last follow-up. This outcome was estimated using the Kaplan Meier method.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00072475 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 22, 2014)
  • Duration of Response [ Time Frame: 5 yrs ]
    Duration of response (DOR) was defined as the time from response (complete remission, partial remission or hematologic improvement) to progression or death of any cause. Responding and alive patients were censored at the date of last follow-up. The median DOR with 95% CI was estimated using the Kaplan Meier method. Response was measured by International Standardized Response Criteria for MDS (described in above outcome measure).
  • Overall Survival [ Time Frame: Duration of study (up to 5 years) ]
    Overall survival (OS) as the interval from the on-study date until death. OS was estimated using the Kaplan Meier method.
  • Progression-free Survival [ Time Frame: Duration of study (up to 5 years) ]
    Progression free survival (PFS) was defined as the time from registration to progression or death of any cause. Progression free and alive patients were censored at the date of last clinical assessment. The median PFS with 95% CI was estimated using the Kaplan Meier method. Progression is defined as
    • For patients with <5% bone marrow blasts: ≥50% increase in blasts to >5% blasts
    • For patients with 5-10% bone marrow blasts: ≥50% increase to >10% blasts
    • For patients with 10-19% bone marrow blasts: increase to ≥20% blasts
    • One or more of the following: 50% or greater decrement from maximum remission/response levels in ANC < 1.5 K/L or PLT< 100 K/L, or reduction in HGB by at least 2 g/dL or becoming transfusion dependent
    Progression after HI: Includes one or more of the following
    • Decrement of 50% or greater from maximum response levels in ANC < 1.5 K/L or PLT < 100 K/L
    • Reduction in HGB concentration by at least 2 g/dL
    • Becoming transfusion dependent
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vatalanib in Treating Patients With Primary or Secondary Myelodysplastic Syndromes
Official Title  ICMJE A Phase II Study of an Oral VEGF Receptor Tyrosine Kinase Inhibitor (PTK787/ZK222584) (IND #66370, NSC #719335) in Myelodysplastic Syndrome (MDS)
Brief Summary

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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Leukemia
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Neoplasms
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: Vatalanib
Adult patients with MDS receive treatment with vatalanib.
Intervention: Drug: vatalanib
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 21, 2011)
155
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE June 2014
Actual Primary Completion Date November 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00072475
Other Study ID Numbers  ICMJE CALGB-10105
U10CA031946 ( U.S. NIH Grant/Contract )
CALGB-10105
CDR0000339810 ( Registry Identifier: NCI Physician Data Query )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alliance for Clinical Trials in Oncology
Study Sponsor  ICMJE Alliance for Clinical Trials in Oncology
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Study Chair: Pankaj Gupta, MD Veterans Affairs Medical Center - Minneapolis
PRS Account Alliance for Clinical Trials in Oncology
Verification Date July 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP