Completed

Vatalanib in Treating Patients With Primary or Secondary Myelodysplastic Syndromes

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What is being tested

vatalanib

Drug
Who is being recruted

Leukemia

+ Myelodysplastic Syndromes
+ Myelodysplastic/Myeloproliferative Neoplasms
Over 18 Years

See all eligibility criteria

How is the trial designed

Treatment Study

Phase 2
Interventional
Study Start: December 2003

See protocol details

Summary

Principal SponsorAlliance for Clinical Trials in Oncology
Last updated: August 1, 2016
Sourced from a government-validated database.Claim as a partner
Study start date: December 1, 2003Actual date on which the first participant was enrolled.

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. 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.

Official TitleA Phase II Study of an Oral VEGF Receptor Tyrosine Kinase Inhibitor (PTK787/ZK222584) (IND #66370, NSC #719335) in Myelodysplastic Syndrome (MDS) 
Principal SponsorAlliance for Clinical Trials in Oncology
Last updated: August 1, 2016
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
155 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, all participants receive the same treatment. Since there is only one group, there is no need for randomization or assignment to different arms. This type of study is often used to test a new treatment without comparing it to another.

Other Ways to Assign Participants
Randomized allocation: Participants are assigned randomly, like flipping a coin, to ensure fairness and reduce bias.
Non-randomized allocation: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.

How treatments are given to participants
In this study, all participants receive the same treatment. This approach is often used to evaluate the effects of a single intervention without comparing it to another.

Other Ways to Assign Treatments
Parallel assignment: Participants are split into separate groups, each receiving a different treatment.
Cross-over assignment: Participants switch between treatments during the study.
Factorial assignment: Participants receive different combinations of treatments.
Sequential assignment: Participants receive treatments one after another in a specific order, possibly based on individual responses.
Other assignment: Treatment assignment does not follow a standard or predefined design.

How the effectiveness of the treatment is controlled
In a non placebo-controlled study, no participants receive an inert substance (placebo) to compare outcomes. Instead, all participants receive either the experimental treatment or an alternative treatment (often the Standard of Care). This method allows researchers to compare the effects of the experimental treatment with those of a different active intervention, rather than a placebo.

Other Options
Placebo-Controlled: A placebo is used to compare the effects of the experimental treatment with those of an inert substance, isolating the true treatment effect.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind: Participants do not know which treatment they are receiving, but researchers do.
Double-blind: Neither participants nor researchers know which treatment is given.
Triple-blind: Participants, researchers, and outcome assessors do not know which treatment is given.
Quadruple-blind: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
Over 18 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Leukemia
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Neoplasms
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

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
One single intervention group 

is designated in this study

This study does not include a placebo group 

Treatment Groups
Group I
Experimental
Adult patients with MDS receive treatment with vatalanib.
Study Objectives
Primary Objectives

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)

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.
Secondary Objectives

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 (OS) as the interval from the on-study date until death. OS was estimated using the Kaplan Meier method.

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 Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 68 locations
Suspended
Tunnell Cancer Center at Beebe Medical CenterLewes, United StatesSee the location
Suspended
CCOP - Christiana Care Health ServicesNewark, United States
Suspended
Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross HospitalFort Lauderdale, United States
Suspended
Ella Milbank Foshay Cancer Center at Jupiter Medical CenterJupiter, United States
Completed68 Study Centers