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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
Open (Enrolling)
Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms

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Trial Information

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



- 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.


- 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

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

Inclusion Criteria


- 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

- No prior leukemia (i.e., 20% or greater blasts)

- No prior primary or metastatic brain tumor or carcinomatous meningitis



- 18 and over

Performance status

- WHO 0-2

Life expectancy

- Not specified


- See Disease Characteristics


- 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


- 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


- 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)


- No pulmonary embolism within the past 6 months


- 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


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)


- 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

Endocrine therapy

- More than 1 month since prior corticosteroids for MDS

- More than 1 month since prior androgens for MDS


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


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

- 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


- No prior cytotoxic therapy for MDS

- More than 1 month since prior administration of any of the following medications for

- 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:


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:


Principal Investigator

Pankaj Gupta, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Veterans Affairs Medical Center - Minneapolis


United States: Food and Drug Administration

Study ID:




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



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