Vatalanib in Treating Patients With Primary or Secondary Myelodysplastic Syndromes

• Sponsor: Alliance for Clinical Trials in Oncology (Other)
• Overall Status: Completed
• CT.gov ID: NCT00072475
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 155
• Locations: 68
• Arm: 1
• Duration (Months): 126
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms	Drug: vatalanib	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 155 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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)
• Study Start Date: Dec 1, 2003
• Actual Primary Completion Date: Nov 1, 2008
• Actual Study Completion Date: Jun 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vatalanib Adult patients with MDS receive treatment with vatalanib.	Drug: 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 Names: PTK787/ZK 222584

Outcome Measures

Primary Outcome Measures

1. 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)

2. 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.

Secondary Outcome Measures

1. 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).

2. 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.

3. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tunnell Cancer Center at Beebe Medical Center	Lewes	Delaware	United States	19958
2	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
3	Michael and Dianne Bienes Comprehensive Cancer Center at Holy Cross Hospital	Fort Lauderdale	Florida	United States	33308
4	Ella Milbank Foshay Cancer Center at Jupiter Medical Center	Jupiter	Florida	United States	33458
5	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
6	Graham Hospital	Canton	Illinois	United States	61520
7	Memorial Hospital	Carthage	Illinois	United States	62321
8	Eureka Community Hospital	Eureka	Illinois	United States	61530
9	Evanston Northwestern Healthcare - Evanston Hospital	Evanston	Illinois	United States	60201-1781
10	Galesburg Clinic, PC	Galesburg	Illinois	United States	61401
11	Galesburg Cottage Hospital	Galesburg	Illinois	United States	61401
12	Mason District Hospital	Havana	Illinois	United States	62644
13	Hopedale Medical Complex	Hopedale	Illinois	United States	61747
14	McDonough District Hospital	Macomb	Illinois	United States	61455
15	BroMenn Regional Medical Center	Normal	Illinois	United States	61761
16	Community Cancer Center	Normal	Illinois	United States	61761
17	Community Hospital of Ottawa	Ottawa	Illinois	United States	61350
18	Oncology Hematology Associates of Central Illinois, PC - Ottawa	Ottawa	Illinois	United States	61350
19	Cancer Treatment Center at Pekin Hospital	Pekin	Illinois	United States	61554
20	Proctor Hospital	Peoria	Illinois	United States	61614
21	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615
22	Oncology Hematology Associates of Central Illinois, PC - Peoria	Peoria	Illinois	United States	61615
23	Methodist Medical Center of Illinois	Peoria	Illinois	United States	61636
24	Illinois Valley Community Hospital	Peru	Illinois	United States	61354
25	Perry Memorial Hospital	Princeton	Illinois	United States	61356
26	Center for Cancer Care at OSF Saint Anthony Medical Center	Rockford	Illinois	United States	61108
27	St. Margaret's Hospital	Spring Valley	Illinois	United States	61362
28	Elkhart General Hospital	Elkhart	Indiana	United States	46515
29	Fort Wayne Medical Oncology and Hematology	Fort Wayne	Indiana	United States	46815
30	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
31	Memorial Hospital of South Bend	South Bend	Indiana	United States	46601
32	Central Maine Comprehensive Cancer Center at Central Maine Medical Center	Lewiston	Maine	United States	04240
33	Union Hospital Cancer Program at Union Hospital	Elkton MD	Maryland	United States	21921
34	Lakeland Regional Cancer Care Center - St. Joseph	St. Joseph	Michigan	United States	49085
35	Veterans Affairs Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55417
36	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri	United States	65203
37	CCOP - Kansas City	Kansas City	Missouri	United States	64131
38	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri	United States	63110
39	Callahan Cancer Center at Great Plains Regional Medical Center	North Platte	Nebraska	United States	69103
40	CCOP - Missouri Valley Cancer Consortium	Omaha	Nebraska	United States	68106
41	Methodist Estabrook Cancer Center	Omaha	Nebraska	United States	68114
42	Immanuel Medical Center	Omaha	Nebraska	United States	68122
43	Alegant Health Cancer Center at Bergan Mercy Medical Center	Omaha	Nebraska	United States	68124
44	Creighton University Medical Center	Omaha	Nebraska	United States	68131-2197
45	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-6805
46	Cancer Institute of New Jersey at Cooper - Voorhees	Voorhees	New Jersey	United States	08043
47	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
48	Don Monti Comprehensive Cancer Center at North Shore University Hospital	Manhasset	New York	United States	11030
49	Long Island Jewish Medical Center	New Hyde Park	New York	United States	11042
50	Mount Sinai Medical Center	New York	New York	United States	10029
51	SUNY Upstate Medical University Hospital	Syracuse	New York	United States	13210
52	Veterans Affairs Medical Center - Syracuse	Syracuse	New York	United States	13210
53	Faxton Regional Cancer Center	Utica	New York	United States	13502
54	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7295
55	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina	United States	28233-3549
56	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
57	Wayne Memorial Hospital, Incorporated	Goldsboro	North Carolina	United States	27534
58	Pardee Memorial Hospital	Hendersonville	North Carolina	United States	28791
59	Kinston Medical Specialists	Kinston	North Carolina	United States	28501
60	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina	United States	27157-1096
61	Oklahoma University Cancer Institute	Oklahoma City	Oklahoma	United States	73104
62	Cancer Care Associates - Mercy Campus	Oklahoma City	Oklahoma	United States	73120
63	Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital	Pittsburgh	Pennsylvania	United States	15224-1791
64	Rhode Island Hospital Comprehensive Cancer Center	Providence	Rhode Island	United States	02903
65	Miriam Hospital	Providence	Rhode Island	United States	02906
66	Mountainview Medical	Berlin	Vermont	United States	05602
67	Fletcher Allen Health Care - University Health Center Campus	Burlington	Vermont	United States	05401
68	Danville Regional Medical Center	Danville	Virginia	United States	24541

Sponsors and Collaborators

• Alliance for Clinical Trials in Oncology
• National Cancer Institute (NCI)

Investigators

• Study Chair: Pankaj Gupta, MD, Veterans Affairs Medical Center - Minneapolis

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Alliance for Clinical Trials in Oncology
• ClinicalTrials.gov Identifier: NCT00072475
• Other Study ID Numbers: CALGB-10105; U10CA031946; CALGB-10105; CDR0000339810
• First Posted: Nov 6, 2003
• Last Update Posted: Aug 1, 2016
• Last Verified: Jul 1, 2016

• Keywords provided by Alliance for Clinical Trials in Oncology: refractory anemia with excess blasts; refractory anemia with ringed sideroblasts; refractory cytopenia with multilineage dysplasia; chronic myelomonocytic leukemia; de novo myelodysplastic syndromes; secondary myelodysplastic syndromes; myelodysplastic/myeloproliferative neoplasm, unclassifiable; refractory anemia; previously treated myelodysplastic syndromes
• Additional relevant MeSH terms: Preleukemia; Myelodysplastic Syndromes; Myeloproliferative Disorders; Myelodysplastic-Myeloproliferative Diseases; Syndrome; Vatalanib

Study Results

Participant Flow

Recruitment Details	A total of 155 participants were enrolled between December 2003 and April 2008.
Pre-assignment Detail	Of the 155 participants recruited, 2 participants cancelled prior to starting treatment; 7 were determined to have AML at registration and 4 had diagnosis other than MDS. Thus 142 participants were evaluable for response and 153 for adverse events.

Arm/Group Title	Vatalanib
Arm/Group Description	Adult patients with MDS receive treatment with vatalanib. 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)
Period Title: Overall Study
STARTED	142
COMPLETED	45
NOT COMPLETED	97

Baseline Characteristics

Arm/Group Title	Vatalanib
Arm/Group Description	Adult patients with MDS receive treatment with vatalanib. 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)
Overall Participants	142
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	71
Sex: Female, Male (Count of Participants)
Female	52 36.6%
Male	90 63.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	3 2.1%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 2.8%
White	133 93.7%
More than one race	1 0.7%
Unknown or Not Reported	1 0.7%
Region of Enrollment (participants) [Number]
United States	142 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Response
Description	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 Frame	Duration of study (up to 5 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vatalanib
Arm/Group Description	Adult patients with MDS receive treatment with vatalanib. 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)
Measure Participants	142
Complete Remission	0 0%
Partial Remission	0 0%
HI-E Major	3 2.1%
HI-E Minor	1 0.7%
HI-P Major	2 1.4%
HI-P Minor	1 0.7%
HI-N Major	0 0%
HI-N Minor	0 0%

2. Secondary Outcome

Title	Duration of Response
Description	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).
Time Frame	5 yrs

Outcome Measure Data

Analysis Population Description

Per the description, only patients who achieved a response were evaluable for this outcome.

Arm/Group Title	Vatalanib
Arm/Group Description	Adult patients with MDS receive treatment with vatalanib. 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)
Measure Participants	7
Median (95% Confidence Interval) [months]	6

3. Secondary Outcome

Title	Overall Survival
Description	Overall survival (OS) as the interval from the on-study date until death. OS was estimated using the Kaplan Meier method.
Time Frame	Duration of study (up to 5 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vatalanib
Arm/Group Description	Adult patients with MDS receive treatment with vatalanib. 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)
Measure Participants	142
Median (95% Confidence Interval) [months]	18.9

4. Secondary Outcome

Title	Progression-free Survival
Description	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
Time Frame	Duration of study (up to 5 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vatalanib
Arm/Group Description	Adult patients with MDS receive treatment with vatalanib. 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)
Measure Participants	142
Median (95% Confidence Interval) [months]	10.2

5. Primary Outcome

Title	Time to Transformation to AML
Description	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.
Time Frame	Duration of study (up to 5 years)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vatalanib
Arm/Group Description	Adult patients with MDS receive treatment with vatalanib. 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)
Measure Participants	142
Median (95% Confidence Interval) [months]	17.2

Adverse Events

Arm/Group Title	Vatalanib
Arm/Group Description	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)
All Cause Mortality
	Vatalanib
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Vatalanib
	Affected / at Risk (%)	# Events
Total	51/153 (33.3%)
Blood and lymphatic system disorders
Disseminated intravascular coagulation	1/153 (0.7%)	1
Febrile neutropenia	7/153 (4.6%)	8
Hemoglobin decreased	43/153 (28.1%)	48
Hemolysis	1/153 (0.7%)	1
Cardiac disorders
Arrhythmia supraventricular	1/153 (0.7%)	1
Atrial fibrillation	1/153 (0.7%)	1
Pericardial effusion	1/153 (0.7%)	1
Sinus tachycardia	1/153 (0.7%)	1
Ear and labyrinth disorders
Tinnitus	1/153 (0.7%)	1
Eye disorders
Vision blurred	2/153 (1.3%)	2
Gastrointestinal disorders
Abdominal pain	4/153 (2.6%)	4
Ascites	1/153 (0.7%)	1
Colonic hemorrhage	1/153 (0.7%)	1
Constipation	3/153 (2%)	3
Diarrhea	21/153 (13.7%)	23
Duodenal hemorrhage	1/153 (0.7%)	1
Dyspepsia	5/153 (3.3%)	6
Ear, nose and throat examination abnormal	2/153 (1.3%)	2
Esophageal hemorrhage	1/153 (0.7%)	1
Esophagitis	1/153 (0.7%)	1
Flatulence	1/153 (0.7%)	1
Gastritis	3/153 (2%)	3
Gastrointestinal disorder	4/153 (2.6%)	4
Lower gastrointestinal hemorrhage	1/153 (0.7%)	1
Mucositis oral	2/153 (1.3%)	2
Nausea	30/153 (19.6%)	33
Oral hemorrhage	1/153 (0.7%)	1
Oral pain	1/153 (0.7%)	1
Pancreatitis	1/153 (0.7%)	1
Rectal hemorrhage	2/153 (1.3%)	2
Small intestinal obstruction	2/153 (1.3%)	2
Vomiting	28/153 (18.3%)	31
General disorders
Chest pain	2/153 (1.3%)	2
Chills	5/153 (3.3%)	5
Death NOS	2/153 (1.3%)	2
Edema limbs	5/153 (3.3%)	6
Fatigue	35/153 (22.9%)	41
Fever	8/153 (5.2%)	8
Hypothermia	1/153 (0.7%)	1
Localized edema	1/153 (0.7%)	1
Pain	3/153 (2%)	4
Sudden death	1/153 (0.7%)	1
Hepatobiliary disorders
Cholecystitis	1/153 (0.7%)	1
Gallbladder pain	1/153 (0.7%)	1
Immune system disorders
Hypersensitivity	1/153 (0.7%)	1
Infections and infestations
Bladder infection	1/153 (0.7%)	1
Catheter related infection	1/153 (0.7%)	1
Duodenal infection	1/153 (0.7%)	1
Gingival infection	1/153 (0.7%)	1
Infection	1/153 (0.7%)	1
Infection without neutropenia	2/153 (1.3%)	2
Sepsis	2/153 (1.3%)	2
Skin infection	1/153 (0.7%)	1
Tooth infection	1/153 (0.7%)	1
Upper respiratory infection	2/153 (1.3%)	2
Urinary tract infection	1/153 (0.7%)	1
Vaginal infection	1/153 (0.7%)	1
Injury, poisoning and procedural complications
Bruising	1/153 (0.7%)	1
Investigations
Activated partial thromboplastin time prolonged	3/153 (2%)	3
Alanine aminotransferase increased	10/153 (6.5%)	11
Alkaline phosphatase	1/153 (0.7%)	1
Alkaline phosphatase increased	7/153 (4.6%)	7
Aspartate aminotransferase increased	12/153 (7.8%)	13
Blood bilirubin increased	6/153 (3.9%)	6
Cardiac troponin I increased	1/153 (0.7%)	1
Coagulopathy	1/153 (0.7%)	1
Creatinine increased	7/153 (4.6%)	8
Electrocardiogram QTc interval prolonged	1/153 (0.7%)	1
Gamma-glutamyltransferase increased	2/153 (1.3%)	2
INR increased	2/153 (1.3%)	2
Laboratory test abnormal	2/153 (1.3%)	2
Leukocyte count decreased	6/153 (3.9%)	6
Lymphocyte count decreased	2/153 (1.3%)	2
Neutrophil count decreased	26/153 (17%)	30
Platelet count decreased	41/153 (26.8%)	47
Serum cholesterol increased	1/153 (0.7%)	1
Weight gain	1/153 (0.7%)	1
Weight loss	5/153 (3.3%)	5
Metabolism and nutrition disorders
Anorexia	11/153 (7.2%)	12
Blood glucose increased	13/153 (8.5%)	16
Blood uric acid increased	2/153 (1.3%)	2
Dehydration	8/153 (5.2%)	9
Serum albumin decreased	9/153 (5.9%)	9
Serum calcium decreased	12/153 (7.8%)	13
Serum calcium increased	1/153 (0.7%)	1
Serum glucose decreased	3/153 (2%)	4
Serum magnesium decreased	4/153 (2.6%)	6
Serum magnesium increased	2/153 (1.3%)	2
Serum phosphate decreased	3/153 (2%)	3
Serum potassium decreased	7/153 (4.6%)	8
Serum potassium increased	3/153 (2%)	3
Serum sodium decreased	8/153 (5.2%)	9
Serum sodium increased	3/153 (2%)	3
Serum triglycerides increased	2/153 (1.3%)	3
Musculoskeletal and connective tissue disorders
Arthralgia	4/153 (2.6%)	4
Arthritis	1/153 (0.7%)	2
Chest wall pain	2/153 (1.3%)	2
Muscle weakness	4/153 (2.6%)	4
Muscle weakness lower limb	1/153 (0.7%)	1
Neck pain	1/153 (0.7%)	1
Pain in extremity	4/153 (2.6%)	4
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Treatment related secondary malignancy	1/153 (0.7%)	1
Nervous system disorders
Ataxia	6/153 (3.9%)	6
Depressed level of consciousness	1/153 (0.7%)	1
Dizziness	14/153 (9.2%)	14
Extrapyramidal disorder	2/153 (1.3%)	2
Headache	10/153 (6.5%)	10
Ischemia cerebrovascular	3/153 (2%)	3
Neurological disorder NOS	2/153 (1.3%)	2
Peripheral motor neuropathy	1/153 (0.7%)	1
Peripheral sensory neuropathy	1/153 (0.7%)	1
Speech disorder	2/153 (1.3%)	2
Syncope	2/153 (1.3%)	2
Tremor	1/153 (0.7%)	1
Psychiatric disorders
Agitation	1/153 (0.7%)	1
Anxiety	2/153 (1.3%)	2
Confusion	7/153 (4.6%)	7
Depression	2/153 (1.3%)	3
Insomnia	2/153 (1.3%)	2
Renal and urinary disorders
Bladder pain	1/153 (0.7%)	1
Hemorrhage urinary tract	4/153 (2.6%)	4
Proteinuria	10/153 (6.5%)	12
Renal failure	1/153 (0.7%)	1
Urinary frequency	1/153 (0.7%)	1
Urinary incontinence	2/153 (1.3%)	2
Urinary retention	1/153 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	2/153 (1.3%)	2
Cough	8/153 (5.2%)	8
Dyspnea	11/153 (7.2%)	11
Dyspnea (shortness of breath)	1/153 (0.7%)	1
Epistaxis	8/153 (5.2%)	9
Hypoxia	1/153 (0.7%)	1
Pharyngeal examination abnormal	2/153 (1.3%)	2
Pharyngolaryngeal pain	1/153 (0.7%)	1
Pleural effusion	1/153 (0.7%)	1
Pleuritic pain	1/153 (0.7%)	1
Pneumonitis	2/153 (1.3%)	2
Respiratory tract hemorrhage	1/153 (0.7%)	1
Tracheoscopy abnormal	1/153 (0.7%)	1
Voice alteration	3/153 (2%)	3
Skin and subcutaneous tissue disorders
Dry skin	1/153 (0.7%)	1
Hand-and-foot syndrome	1/153 (0.7%)	1
Petechiae	3/153 (2%)	3
Photosensitivity	1/153 (0.7%)	1
Pigmentation changes (e.g., vitiligo)	1/153 (0.7%)	1
Pruritus	2/153 (1.3%)	2
Rash desquamating	3/153 (2%)	3
Skin disorder	1/153 (0.7%)	1
Sweating	3/153 (2%)	3
Vascular disorders
Hematoma	1/153 (0.7%)	1
Hemorrhage	1/153 (0.7%)	1
Hemorrhage/bleeding with grade 3 or 4 thrombocytopenia	1/153 (0.7%)	1
Hypertension	7/153 (4.6%)	9
Hypotension	5/153 (3.3%)	5
Other (Not Including Serious) Adverse Events
	Vatalanib
	Affected / at Risk (%)	# Events
Total	134/153 (87.6%)
Blood and lymphatic system disorders
Blood disorder	1/153 (0.7%)	2
Febrile neutropenia	12/153 (7.8%)	12
Hemoglobin decreased	121/153 (79.1%)	324
Hemolysis	1/153 (0.7%)	1
Spleen disorder	1/153 (0.7%)	1
Transfusion: pRBCs for pediatric BMT studies, if specified in the protocol.	1/153 (0.7%)	1
Cardiac disorders
Arrhythmia	1/153 (0.7%)	1
Atrial flutter	1/153 (0.7%)	1
Cardiac disorder	2/153 (1.3%)	2
Conduction disorder	1/153 (0.7%)	1
Left ventricular failure	4/153 (2.6%)	4
Myocardial ischemia	2/153 (1.3%)	2
Palpitations	4/153 (2.6%)	6
Sinus tachycardia	3/153 (2%)	3
Ventricular tachycardia	1/153 (0.7%)	1
Ear and labyrinth disorders
External ear inflammation	1/153 (0.7%)	1
Tinnitus	1/153 (0.7%)	3
Endocrine disorders
Endocrine disorder	2/153 (1.3%)	2
Hypothyroidism	2/153 (1.3%)	2
Eye disorders
Diplopia	1/153 (0.7%)	1
Eye disorder	2/153 (1.3%)	2
Eye pain	1/153 (0.7%)	1
Flashing vision	2/153 (1.3%)	2
Glaucoma	1/153 (0.7%)	1
Vision blurred	2/153 (1.3%)	2
Gastrointestinal disorders
Abdominal pain	4/153 (2.6%)	4
Anal hemorrhage	1/153 (0.7%)	1
Cheilitis	1/153 (0.7%)	1
Colitis	1/153 (0.7%)	1
Constipation	23/153 (15%)	28
Diarrhea	45/153 (29.4%)	71
Dry mouth	3/153 (2%)	3
Dyspepsia	8/153 (5.2%)	9
Dysphagia	2/153 (1.3%)	2
Ear, nose and throat examination abnormal	7/153 (4.6%)	8
Esophageal mucositis	1/153 (0.7%)	1
Esophagitis	1/153 (0.7%)	1
Flatulence	1/153 (0.7%)	1
Gastric hemorrhage	3/153 (2%)	3
Gastrointestinal disorder	6/153 (3.9%)	8
Hemorrhoids	3/153 (2%)	4
Lower gastrointestinal hemorrhage	2/153 (1.3%)	2
Mucositis oral	6/153 (3.9%)	6
Nausea	80/153 (52.3%)	135
Oral hemorrhage	1/153 (0.7%)	1
Oral pain	2/153 (1.3%)	2
Proctitis	1/153 (0.7%)	1
Rectal hemorrhage	1/153 (0.7%)	1
Stomach pain	2/153 (1.3%)	2
Toothache	3/153 (2%)	3
Vomiting	52/153 (34%)	70
General disorders
Chest pain	4/153 (2.6%)	4
Chills	6/153 (3.9%)	8
Death NOS	2/153 (1.3%)	2
Edema limbs	15/153 (9.8%)	21
Fatigue	116/153 (75.8%)	233
Fever	12/153 (7.8%)	16
Gait abnormal	1/153 (0.7%)	2
Injection site reaction	1/153 (0.7%)	1
Pain	11/153 (7.2%)	13
Visceral edema	1/153 (0.7%)	2
Immune system disorders
Hypersensitivity	1/153 (0.7%)	1
Immune system disorder	1/153 (0.7%)	1
Infections and infestations
Bladder infection	1/153 (0.7%)	1
Bronchitis	1/153 (0.7%)	1
Catheter related infection	2/153 (1.3%)	2
Duodenal infection	1/153 (0.7%)	1
Esophageal infection	1/153 (0.7%)	1
Infection	5/153 (3.3%)	5
Infection with grade 3 or 4 neutropenia	1/153 (0.7%)	1
Infection without neutropenia	1/153 (0.7%)	1
Mucosal infection	1/153 (0.7%)	1
Opportunistic infection	1/153 (0.7%)	1
Otitis media	1/153 (0.7%)	1
Pneumonia	6/153 (3.9%)	6
Rhinitis infective	1/153 (0.7%)	1
Sepsis	2/153 (1.3%)	2
Sinusitis	3/153 (2%)	3
Skin infection	3/153 (2%)	3
Soft tissue infection	1/153 (0.7%)	1
Tooth infection	3/153 (2%)	3
Upper respiratory infection	4/153 (2.6%)	5
Urinary tract infection	2/153 (1.3%)	2
Injury, poisoning and procedural complications
Bruising	7/153 (4.6%)	7
Fracture	1/153 (0.7%)	1
Investigations
Activated partial thromboplastin time prolonged	3/153 (2%)	6
Alanine aminotransferase increased	27/153 (17.6%)	41
Alkaline phosphatase increased	13/153 (8.5%)	18
Aspartate aminotransferase increased	25/153 (16.3%)	36
Blood bilirubin increased	8/153 (5.2%)	12
Coagulopathy	2/153 (1.3%)	3
Creatinine increased	9/153 (5.9%)	14
Electrocardiogram QTc interval prolonged	1/153 (0.7%)	1
Gamma-glutamyltransferase increased	3/153 (2%)	3
INR increased	3/153 (2%)	4
Laboratory test abnormal	7/153 (4.6%)	8
Leukocyte count decreased	15/153 (9.8%)	29
Lipase increased	1/153 (0.7%)	1
Lymphocyte count decreased	2/153 (1.3%)	3
Neutrophil count decreased	88/153 (57.5%)	198
Pancreatic enzymes decreased	1/153 (0.7%)	1
Platelet count decreased	100/153 (65.4%)	226
Serum cholesterol increased	4/153 (2.6%)	7
Weight gain	1/153 (0.7%)	1
Weight loss	15/153 (9.8%)	15
Metabolism and nutrition disorders
Anorexia	26/153 (17%)	36
Blood glucose increased	37/153 (24.2%)	70
Blood uric acid increased	1/153 (0.7%)	2
Dehydration	3/153 (2%)	3
Iron overload	3/153 (2%)	4
Serum albumin decreased	12/153 (7.8%)	15
Serum calcium decreased	11/153 (7.2%)	16
Serum calcium increased	2/153 (1.3%)	3
Serum glucose decreased	5/153 (3.3%)	5
Serum magnesium decreased	3/153 (2%)	3
Serum magnesium increased	2/153 (1.3%)	3
Serum potassium decreased	7/153 (4.6%)	8
Serum potassium increased	3/153 (2%)	3
Serum sodium decreased	7/153 (4.6%)	9
Serum sodium increased	2/153 (1.3%)	2
Serum triglycerides increased	7/153 (4.6%)	7
Musculoskeletal and connective tissue disorders
Arthralgia	10/153 (6.5%)	16
Arthritis	2/153 (1.3%)	2
Back pain	10/153 (6.5%)	14
Bone pain	5/153 (3.3%)	5
Chest wall pain	3/153 (2%)	3
Muscle weakness	5/153 (3.3%)	9
Muscle weakness upper limb	1/153 (0.7%)	1
Musculoskeletal disorder	6/153 (3.9%)	6
Myalgia	9/153 (5.9%)	9
Pain in extremity	5/153 (3.3%)	8
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplasia	1/153 (0.7%)	1
Nervous system disorders
Ataxia	15/153 (9.8%)	17
Cognitive disturbance	1/153 (0.7%)	1
Dizziness	60/153 (39.2%)	82
Dysgeusia	2/153 (1.3%)	2
Extrapyramidal disorder	1/153 (0.7%)	1
Headache	19/153 (12.4%)	22
Intracranial hemorrhage	1/153 (0.7%)	1
Memory impairment	3/153 (2%)	5
Mini mental status examination abnormal	1/153 (0.7%)	1
Neuralgia	1/153 (0.7%)	2
Neurological disorder NOS	3/153 (2%)	3
Peripheral motor neuropathy	5/153 (3.3%)	6
Peripheral sensory neuropathy	11/153 (7.2%)	16
Speech disorder	2/153 (1.3%)	2
Syncope	1/153 (0.7%)	1
Tremor	3/153 (2%)	4
Vagus nerve disorder	1/153 (0.7%)	2
Psychiatric disorders
Agitation	1/153 (0.7%)	1
Anxiety	3/153 (2%)	3
Confusion	5/153 (3.3%)	6
Depression	3/153 (2%)	3
Euphoria	2/153 (1.3%)	2
Insomnia	9/153 (5.9%)	12
Renal and urinary disorders
Cystitis	2/153 (1.3%)	2
Hemorrhage urinary tract	2/153 (1.3%)	4
Kidney pain	1/153 (0.7%)	1
Proteinuria	30/153 (19.6%)	47
Urinary frequency	2/153 (1.3%)	2
Urinary incontinence	1/153 (0.7%)	1
Urine discoloration	1/153 (0.7%)	1
Urogenital disorder	2/153 (1.3%)	2
Reproductive system and breast disorders
Scrotal pain	1/153 (0.7%)	1
Vaginal hemorrhage	1/153 (0.7%)	1
Vaginal inflammation	1/153 (0.7%)	1
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis	5/153 (3.3%)	6
Bronchospasm	1/153 (0.7%)	1
Cough	19/153 (12.4%)	27
Dyspnea	37/153 (24.2%)	51
Dyspnea (shortness of breath)	4/153 (2.6%)	4
Epistaxis	14/153 (9.2%)	18
Hemoptysis	1/153 (0.7%)	1
Hypoxia	1/153 (0.7%)	1
Pharyngolaryngeal pain	2/153 (1.3%)	2
Pleural effusion	1/153 (0.7%)	1
Pneumonitis	4/153 (2.6%)	4
Respiratory disorder	3/153 (2%)	3
Respiratory tract hemorrhage	1/153 (0.7%)	1
Voice alteration	4/153 (2.6%)	6
Skin and subcutaneous tissue disorders
Alopecia	1/153 (0.7%)	1
Dry skin	6/153 (3.9%)	6
Petechiae	6/153 (3.9%)	7
Pruritus	6/153 (3.9%)	7
Rash desquamating	20/153 (13.1%)	25
Skin disorder	9/153 (5.9%)	9
Sweating	6/153 (3.9%)	7
Urticaria	3/153 (2%)	3
Vascular disorders
Hematoma	3/153 (2%)	4
Hot flashes	1/153 (0.7%)	1
Hypertension	10/153 (6.5%)	15
Hypotension	4/153 (2.6%)	4
Thrombosis	2/153 (1.3%)	3
Vascular disorder	2/153 (1.3%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.