Vatalanib in Treating Patients With Primary or Secondary Myelodysplastic Syndromes
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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of an Oral VEGF Receptor Tyrosine Kinase Inhibitor (PTK787/ZK222584) (IND #66370, NSC #719335) in Myelodysplastic Syndrome (MDS)|
- Number of Participants With Response [ Time Frame: Duration of study (up to 5 years) ] [ Designated as safety issue: No ]
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.
- 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)
- Time to Transformation to AML [ Time Frame: Duration of study (up to 5 years) ] [ Designated as safety issue: No ]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.
- Duration of Response [ Time Frame: 5 yrs ] [ Designated as safety issue: No ]
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).
- Overall Survival [ Time Frame: Duration of study (up to 5 years) ] [ Designated as safety issue: No ]Overall survival (OS) as the interval from the on-study date until death. OS was estimated using the Kaplan Meier method.
- Progression-free Survival [ Time Frame: Duration of study (up to 5 years) ] [ Designated as safety issue: No ]
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
|Study Start Date:||December 2003|
|Study Completion Date:||December 2013|
|Primary Completion Date:||November 2008 (Final data collection date for primary outcome measure)|
Adult patients with MDS receive treatment with vatalanib.
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)
Other Name: PTK787/ZK 222584
- 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 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00072475
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|Study Chair:||Pankaj Gupta, MD||Veterans Affairs Medical Center - Minneapolis|