Vatalanib in Treating Patients With Primary or Secondary Myelodysplastic Syndromes
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 |
---|---|---|
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
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:
|
Outcome Measures
Primary Outcome Measures
- 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)
- 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
- 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).
- 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.
- 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
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.- CALGB-10105
- U10CA031946
- CALGB-10105
- CDR0000339810
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
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%
|
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
|
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
|
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
|
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
Time Frame | ||
---|---|---|
Adverse Event Reporting Description | ||
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
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.
Results Point of Contact
Name/Title | Pankaj Gupta, M.D. |
---|---|
Organization | University of Minnesota |
Phone | |
gupta013@umn.edu |
- CALGB-10105
- U10CA031946
- CALGB-10105
- CDR0000339810