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A Phase II Study of an Oral VEGF Receptor Tyrosine Kinase Inhibitor (PTK787/ZK222584) (IND #66370, NSC #719335) in Myelodysplastic Syndrome (MDS)


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms

Thank you

Trial Information

A Phase II Study of an Oral VEGF Receptor Tyrosine Kinase Inhibitor (PTK787/ZK222584) (IND #66370, NSC #719335) in Myelodysplastic Syndrome (MDS)


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Hematologic Response rate

Outcome Description:

measured by International Standardized Response Criteria for myelodysplastic syndromes (MDS)

Outcome Time Frame:

5 yrs

Safety Issue:

No

Principal Investigator

Pankaj Gupta, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Veterans Affairs Medical Center - Minneapolis

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000339810

NCT ID:

NCT00072475

Start Date:

December 2003

Completion Date:

December 2013

Related Keywords:

  • Leukemia
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Neoplasms
  • 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
  • Neoplasms
  • Leukemia
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
CCOP - Kansas CityKansas City, Missouri  64131
CCOP - Missouri Valley Cancer ConsortiumOmaha, Nebraska  68131
CCOP - Christiana Care Health ServicesWilmington, Delaware  19899
CCOP - Mount Sinai Medical CenterMiami Beach, Florida  33140
CCOP - Illinois Oncology Research AssociationPeoria, Illinois  61602
Evanston Northwestern Healthcare - Evanston HospitalEvanston, Illinois  60201-1781
Methodist Medical Center of IllinoisPeoria, Illinois  61636
Memorial Hospital of South BendSouth Bend, Indiana  46601
CCOP - Northern Indiana CR ConsortiumSouth Bend, Indiana  46601
Ellis Fischel Cancer Center at University of Missouri - ColumbiaColumbia, Missouri  65203
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel HillChapel Hill, North Carolina  27599-7570
Veterans Affairs Medical Center - MinneapolisMinneapolis, Minnesota  55417
Veterans Affairs Medical Center - SyracuseSyracuse, New York  13210
Fletcher Allen Health Care - University Health Center CampusBurlington, Vermont  05401
Long Island Jewish Medical CenterNew Hyde Park, New York  11040
Mount Sinai Medical CenterNew York, New York  10029
SUNY Upstate Medical University HospitalSyracuse, New York  13210
Presbyterian Cancer Center at Presbyterian HospitalCharlotte, North Carolina  28233-3549
Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096
Rhode Island Hospital Comprehensive Cancer CenterProvidence, Rhode Island  02903
Wayne Memorial Hospital, IncorporatedGoldsboro, North Carolina  27534
UNMC Eppley Cancer Center at the University of Nebraska Medical CenterOmaha, Nebraska  68198-7680
Siteman Cancer Center at Barnes-Jewish Hospital - Saint LouisSt. Louis, Missouri  63110
Don Monti Comprehensive Cancer Center at North Shore University HospitalManhasset, New York  11030
Oklahoma University Cancer InstituteOklahoma City, Oklahoma  73104
Methodist Estabrook Cancer CenterOmaha, Nebraska  68114-4199
Elkhart General HospitalElkhart, Indiana  46515
Lakeland Regional Cancer Care Center - St. JosephSt. Joseph, Michigan  49085
Ella Milbank Foshay Cancer Center at Jupiter Medical CenterJupiter, Florida  33458
Graham HospitalCanton, Illinois  61520
Memorial HospitalCarthage, Illinois  62321
Eureka Community HospitalEureka, Illinois  61530
Galesburg Cottage HospitalGalesburg, Illinois  61401
Mason District HospitalHavana, Illinois  62644
Hopedale Medical ComplexHopedale, Illinois  61747
McDonough District HospitalMacomb, Illinois  61455
BroMenn Regional Medical CenterNormal, Illinois  61761
Community Cancer CenterNormal, Illinois  61761
Community Hospital of OttawaOttawa, Illinois  61350
Oncology Hematology Associates of Central Illinois, PC - OttawaOttawa, Illinois  61350
Cancer Treatment Center at Pekin HospitalPekin, Illinois  61554
Oncology Hematology Associates of Central Illinois, PC - PeoriaPeoria, Illinois  61615
Proctor HospitalPeoria, Illinois  61614
Illinois Valley Community HospitalPeru, Illinois  61354
Perry Memorial HospitalPrinceton, Illinois  61356
St. Margaret's HospitalSpring Valley, Illinois  61362
Fort Wayne Medical Oncology and HematologyFort Wayne, Indiana  46815
Immanuel Medical CenterOmaha, Nebraska  68122
Creighton University Medical CenterOmaha, Nebraska  68131-2197
Cancer Institute of New Jersey at Cooper - VoorheesVoorhees, New Jersey  08043
Mountainview MedicalBerlin, Vermont  05602
Danville Regional Medical CenterDanville, Virginia  24541
Western Pennsylvania Cancer Institute at Western Pennsylvania HospitalPittsburgh, Pennsylvania  15224-1791
Tunnell Cancer Center at Beebe Medical CenterLewes, Delaware  19958
Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross HospitalFort Lauderdale, Florida  33308
Union Hospital Cancer Program at Union HospitalElkton MD, Maryland  21921
Alegant Health Cancer Center at Bergan Mercy Medical CenterOmaha, Nebraska  68124
Cancer Care Associates - Mercy CampusOklahoma City, Oklahoma  73120
Pardee Memorial HospitalHendersonville, North Carolina  28791
Kinston Medical SpecialistsKinston, North Carolina  28501
Miriam HospitalProvidence, Rhode Island  02906
Center for Cancer Care at OSF Saint Anthony Medical CenterRockford, Illinois  61108
Galesburg Clinic, PCGalesburg, Illinois  61401
Faxton Regional Cancer CenterUtica, New York  13502
Callahan Cancer Center at Great Plains Regional Medical CenterNorth Platte, Nebraska  69103
Central Maine Comprehensive Cancer Center at Central Maine Medical CenterLewiston, Maine  04240