Vatalanib in Treating Patients With Primary or Secondary Myelodysplastic Syndromes

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology ( Cancer and Leukemia Group B )
ClinicalTrials.gov Identifier:
NCT00072475
First received: November 4, 2003
Last updated: May 22, 2014
Last verified: May 2014
  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 2

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 Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Number of Participants With Response [ Time Frame: Duration of study (up to 5 years) ] [ Designated as safety issue: No ]

    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) ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Duration of Response [ Time Frame: 5 yrs ] [ Designated as safety issue: No ]

    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) ] [ Designated as safety issue: No ]
    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) ] [ Designated as safety issue: No ]

    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


Enrollment: 155
Study Start Date: December 2003
Study Completion Date: December 2013
Primary Completion Date: November 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
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: NCT00072475

  Hide Study Locations
Locations
United States, Delaware
Tunnell Cancer Center at Beebe Medical Center
Lewes, Delaware, United States, 19958
CCOP - Christiana Care Health Services
Newark, Delaware, United States, 19713
United States, Florida
Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
Fort Lauderdale, Florida, United States, 33308
Ella Milbank Foshay Cancer Center at Jupiter Medical Center
Jupiter, Florida, United States, 33458
CCOP - Mount Sinai Medical Center
Miami Beach, Florida, United States, 33140
United States, Illinois
Graham Hospital
Canton, Illinois, United States, 61520
Memorial Hospital
Carthage, Illinois, United States, 62321
Eureka Community Hospital
Eureka, Illinois, United States, 61530
Evanston Northwestern Healthcare - Evanston Hospital
Evanston, Illinois, United States, 60201-1781
Galesburg Clinic, PC
Galesburg, Illinois, United States, 61401
Galesburg Cottage Hospital
Galesburg, Illinois, United States, 61401
Mason District Hospital
Havana, Illinois, United States, 62644
Hopedale Medical Complex
Hopedale, Illinois, United States, 61747
McDonough District Hospital
Macomb, Illinois, United States, 61455
BroMenn Regional Medical Center
Normal, Illinois, United States, 61761
Community Cancer Center
Normal, Illinois, United States, 61761
Community Hospital of Ottawa
Ottawa, Illinois, United States, 61350
Oncology Hematology Associates of Central Illinois, PC - Ottawa
Ottawa, Illinois, United States, 61350
Cancer Treatment Center at Pekin Hospital
Pekin, Illinois, United States, 61554
CCOP - Illinois Oncology Research Association
Peoria, Illinois, United States, 61615
Proctor Hospital
Peoria, Illinois, United States, 61614
Methodist Medical Center of Illinois
Peoria, Illinois, United States, 61636
Oncology Hematology Associates of Central Illinois, PC - Peoria
Peoria, Illinois, United States, 61615
Illinois Valley Community Hospital
Peru, Illinois, United States, 61354
Perry Memorial Hospital
Princeton, Illinois, United States, 61356
Center for Cancer Care at OSF Saint Anthony Medical Center
Rockford, Illinois, United States, 61108
St. Margaret's Hospital
Spring Valley, Illinois, United States, 61362
United States, Indiana
Elkhart General Hospital
Elkhart, Indiana, United States, 46515
Fort Wayne Medical Oncology and Hematology
Fort Wayne, Indiana, United States, 46815
Memorial Hospital of South Bend
South Bend, Indiana, United States, 46601
CCOP - Northern Indiana CR Consortium
South Bend, Indiana, United States, 46601
United States, Maine
Central Maine Comprehensive Cancer Center at Central Maine Medical Center
Lewiston, Maine, United States, 04240
United States, Maryland
Union Hospital Cancer Program at Union Hospital
Elkton MD, Maryland, United States, 21921
United States, Michigan
Lakeland Regional Cancer Care Center - St. Joseph
St. Joseph, Michigan, United States, 49085
United States, Minnesota
Veterans Affairs Medical Center - Minneapolis
Minneapolis, Minnesota, United States, 55417
United States, Missouri
Ellis Fischel Cancer Center at University of Missouri - Columbia
Columbia, Missouri, United States, 65203
CCOP - Kansas City
Kansas City, Missouri, United States, 64131
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
Saint Louis, Missouri, United States, 63110
United States, Nebraska
Callahan Cancer Center at Great Plains Regional Medical Center
North Platte, Nebraska, United States, 69103
Immanuel Medical Center
Omaha, Nebraska, United States, 68122
CCOP - Missouri Valley Cancer Consortium
Omaha, Nebraska, United States, 68106
Alegant Health Cancer Center at Bergan Mercy Medical Center
Omaha, Nebraska, United States, 68124
Creighton University Medical Center
Omaha, Nebraska, United States, 68131-2197
Methodist Estabrook Cancer Center
Omaha, Nebraska, United States, 68114
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-6805
United States, New Jersey
Cancer Institute of New Jersey at Cooper - Voorhees
Voorhees, New Jersey, United States, 08043
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
Don Monti Comprehensive Cancer Center at North Shore University Hospital
Manhasset, New York, United States, 11030
Long Island Jewish Medical Center
New Hyde Park, New York, United States, 11042
Mount Sinai Medical Center
New York, New York, United States, 10029
SUNY Upstate Medical University Hospital
Syracuse, New York, United States, 13210
Veterans Affairs Medical Center - Syracuse
Syracuse, New York, United States, 13210
Faxton Regional Cancer Center
Utica, New York, United States, 13502
United States, North Carolina
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295
Presbyterian Cancer Center at Presbyterian Hospital
Charlotte, North Carolina, United States, 28233-3549
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
Wayne Memorial Hospital, Incorporated
Goldsboro, North Carolina, United States, 27534
Pardee Memorial Hospital
Hendersonville, North Carolina, United States, 28791
Kinston Medical Specialists
Kinston, North Carolina, United States, 28501
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
United States, Oklahoma
Cancer Care Associates - Mercy Campus
Oklahoma City, Oklahoma, United States, 73120
Oklahoma University Cancer Institute
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, United States, 15224-1791
United States, Rhode Island
Miriam Hospital
Providence, Rhode Island, United States, 02906
Rhode Island Hospital Comprehensive Cancer Center
Providence, Rhode Island, United States, 02903
United States, Vermont
Mountainview Medical
Berlin, Vermont, United States, 05602
Fletcher Allen Health Care - University Health Center Campus
Burlington, Vermont, United States, 05401
United States, Virginia
Danville Regional Medical Center
Danville, Virginia, United States, 24541
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: Alliance for Clinical Trials in Oncology ( 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
Results First Received: May 22, 2014
Last Updated: May 22, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Alliance for Clinical Trials in Oncology:
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 July 20, 2014