Vatalanib in Treating Patients With Primary or Secondary Myelodysplastic Syndromes

Phase 2

Completed

Conditions: Leukemia
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms

Interventions: Drug: vatalanib

Registration Number: NCT00072475

Lead Sponsor: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 155

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Vatalanib	vatalanib	Adult patients with MDS receive treatment with vatalanib.

Primary Outcome Measures

Name	Time	Method
Time to Transformation to AML	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.
Number of Participants With Response	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)

Secondary Outcome Measures

Name	Time	Method
Overall Survival	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.
Duration of Response	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).
Progression-free Survival	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

Trial Locations

Locations (68): Elkhart General Hospital
🇺🇸
Elkhart, Indiana, United States
Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital
🇺🇸
Fort Lauderdale, Florida, United States
Galesburg Clinic, PC
🇺🇸
Galesburg, Illinois, United States
Memorial Hospital of South Bend
🇺🇸
South Bend, Indiana, United States
Cancer Institute of New Jersey at Cooper - Voorhees
🇺🇸
Voorhees, New Jersey, United States
Don Monti Comprehensive Cancer Center at North Shore University Hospital
🇺🇸
Manhasset, New York, United States
SUNY Upstate Medical University Hospital
🇺🇸
Syracuse, New York, United States
Veterans Affairs Medical Center - Syracuse
🇺🇸
Syracuse, New York, United States
Memorial Hospital
🇺🇸
Carthage, Illinois, United States
Eureka Community Hospital
🇺🇸
Eureka, Illinois, United States
Galesburg Cottage Hospital
🇺🇸
Galesburg, Illinois, United States
Mason District Hospital
🇺🇸
Havana, Illinois, United States
Perry Memorial Hospital
🇺🇸
Princeton, Illinois, United States
CCOP - Illinois Oncology Research Association
🇺🇸
Peoria, Illinois, United States
Tunnell Cancer Center at Beebe Medical Center
🇺🇸
Lewes, Delaware, United States
Central Maine Comprehensive Cancer Center at Central Maine Medical Center
🇺🇸
Lewiston, Maine, United States
Veterans Affairs Medical Center - Minneapolis
🇺🇸
Minneapolis, Minnesota, United States
Duke Comprehensive Cancer Center
🇺🇸
Durham, North Carolina, United States
Methodist Medical Center of Illinois
🇺🇸
Peoria, Illinois, United States
Community Hospital of Ottawa
🇺🇸
Ottawa, Illinois, United States
Center for Cancer Care at OSF Saint Anthony Medical Center
🇺🇸
Rockford, Illinois, United States
Fort Wayne Medical Oncology and Hematology
🇺🇸
Fort Wayne, Indiana, United States
CCOP - Northern Indiana CR Consortium
🇺🇸
South Bend, Indiana, United States
Ellis Fischel Cancer Center at University of Missouri - Columbia
🇺🇸
Columbia, Missouri, United States
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
🇺🇸
Saint Louis, Missouri, United States
Mount Sinai Medical Center
🇺🇸
New York, New York, United States
Faxton Regional Cancer Center
🇺🇸
Utica, New York, United States
Pardee Memorial Hospital
🇺🇸
Hendersonville, North Carolina, United States
Alegant Health Cancer Center at Bergan Mercy Medical Center
🇺🇸
Omaha, Nebraska, United States
CCOP - Missouri Valley Cancer Consortium
🇺🇸
Omaha, Nebraska, United States
Methodist Estabrook Cancer Center
🇺🇸
Omaha, Nebraska, United States
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
Immanuel Medical Center
🇺🇸
Omaha, Nebraska, United States
Creighton University Medical Center
🇺🇸
Omaha, Nebraska, United States
Oklahoma University Cancer Institute
🇺🇸
Oklahoma City, Oklahoma, United States
Cancer Care Associates - Mercy Campus
🇺🇸
Oklahoma City, Oklahoma, United States
Ella Milbank Foshay Cancer Center at Jupiter Medical Center
🇺🇸
Jupiter, Florida, United States
CCOP - Mount Sinai Medical Center
🇺🇸
Miami Beach, Florida, United States
Graham Hospital
🇺🇸
Canton, Illinois, United States
Evanston Northwestern Healthcare - Evanston Hospital
🇺🇸
Evanston, Illinois, United States
McDonough District Hospital
🇺🇸
Macomb, Illinois, United States
Oncology Hematology Associates of Central Illinois, PC - Ottawa
🇺🇸
Ottawa, Illinois, United States
Hopedale Medical Complex
🇺🇸
Hopedale, Illinois, United States
BroMenn Regional Medical Center
🇺🇸
Normal, Illinois, United States
Cancer Treatment Center at Pekin Hospital
🇺🇸
Pekin, Illinois, United States
Community Cancer Center
🇺🇸
Normal, Illinois, United States
Proctor Hospital
🇺🇸
Peoria, Illinois, United States
Oncology Hematology Associates of Central Illinois, PC - Peoria
🇺🇸
Peoria, Illinois, United States
Illinois Valley Community Hospital
🇺🇸
Peru, Illinois, United States
St. Margaret's Hospital
🇺🇸
Spring Valley, Illinois, United States
Union Hospital Cancer Program at Union Hospital
🇺🇸
Elkton MD, Maryland, United States
Lakeland Regional Cancer Care Center - St. Joseph
🇺🇸
St. Joseph, Michigan, United States
Callahan Cancer Center at Great Plains Regional Medical Center
🇺🇸
North Platte, Nebraska, United States
Roswell Park Cancer Institute
🇺🇸
Buffalo, New York, United States
Long Island Jewish Medical Center
🇺🇸
New Hyde Park, New York, United States
Presbyterian Cancer Center at Presbyterian Hospital
🇺🇸
Charlotte, North Carolina, United States
Wayne Memorial Hospital, Incorporated
🇺🇸
Goldsboro, North Carolina, United States
Kinston Medical Specialists
🇺🇸
Kinston, North Carolina, United States
Miriam Hospital
🇺🇸
Providence, Rhode Island, United States
Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
🇺🇸
Pittsburgh, Pennsylvania, United States
Rhode Island Hospital Comprehensive Cancer Center
🇺🇸
Providence, Rhode Island, United States
Fletcher Allen Health Care - University Health Center Campus
🇺🇸
Burlington, Vermont, United States
Danville Regional Medical Center
🇺🇸
Danville, Virginia, United States
Mountainview Medical
🇺🇸
Berlin, Vermont, United States
CCOP - Christiana Care Health Services
🇺🇸
Newark, Delaware, United States
CCOP - Kansas City
🇺🇸
Kansas City, Missouri, United States
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
🇺🇸
Chapel Hill, North Carolina, United States
Wake Forest University Comprehensive Cancer Center
🇺🇸
Winston-Salem, North Carolina, United States