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.

Study Timeline

• Study First Submitted: 2003-11-04
• Study First Submitted QC: 2003-11-05
• Study First Posted: 2003-11-06
• Study Start: 2003-12
• Primary Completion: 2008-11
• Results First Submitted: 2014-05-22
• Results First Submitted QC: 2014-05-22
• Study Completion: 2014-06
• Results First Posted: 2014-06-24
• Status Verified: 2016-07
• Last Update Submitted: 2016-07-01
• Last Update Posted: 2016-08-01

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)

Tunnell Cancer Center at Beebe Medical Center; 🇺🇸 Lewes, Delaware, United States

CCOP - Christiana Care Health Services; 🇺🇸 Newark, Delaware, United States

Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital; 🇺🇸 Fort Lauderdale, Florida, 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

Memorial Hospital; 🇺🇸 Carthage, Illinois, United States

Eureka Community Hospital; 🇺🇸 Eureka, Illinois, United States

Evanston Northwestern Healthcare - Evanston Hospital; 🇺🇸 Evanston, Illinois, United States

Galesburg Clinic, PC; 🇺🇸 Galesburg, Illinois, United States

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