Vatalanib in Treating Patients With Primary or Secondary Myelodysplastic Syndromes

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

Sponsors

Lead Sponsor: Alliance for Clinical Trials in Oncology

Collaborator: National Cancer Institute (NCI)

Source Alliance for Clinical Trials in Oncology
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.

Overall Status Completed
Start Date December 2003
Completion Date June 2014
Primary Completion Date November 2008
Phase Phase 2
Study Type Interventional
Primary Outcome
Measure Time Frame
Number of Participants With Response Duration of study (up to 5 years)
Time to Transformation to AML Duration of study (up to 5 years)
Secondary Outcome
Measure Time Frame
Duration of Response 5 yrs
Overall Survival Duration of study (up to 5 years)
Progression-free Survival Duration of study (up to 5 years)
Enrollment 155
Condition
Intervention

Intervention Type: Drug

Intervention Name: vatalanib

Description: 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)

Arm Group Label: Vatalanib

Other Name: PTK787/ZK 222584

Eligibility

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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

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

United States

Verification Date

July 2016

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 1
Arm Group

Label: Vatalanib

Type: Experimental

Description: Adult patients with MDS receive treatment with vatalanib.

Study Design Info

Allocation: N/A

Intervention Model: Single Group Assignment

Primary Purpose: Treatment

Masking: None (Open Label)

Source: ClinicalTrials.gov