A Pilot Study of Decitabine and Vorinostat With Chemotherapy for Relapsed ALL
Study Details
Study Description
Brief Summary
This is a pilot study using decitabine and vorinostat before and during chemotherapy with vincristine, dexamethasone, mitoxantrone, and peg-asparaginase in pediatric patients with acute lymphoblastic leukemia (ALL).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
Decitabine is a demethylating agent and vorinostat is a HDAC inhibitor. The use of demethylating agents and HDAC inhibitors in combination have been previously shown to have synergistic effects in altering neoplastic pathways of cancer cells and be well tolerated in human clinical studies. With the ability of decitabine and vorinostat to alter the abnormal cellular pathways of leukemic blasts and essentially turn off anti-apoptotic proteins, the leukemia cells have become primed for cytotoxic cell kill via chemotherapeutic agents. This study will ask the question as to whether or not the combination of decitabine and vorinostat followed by chemotherapy is feasible and whether it can positively impact outcome in patients with relapsed or refractory acute lymphoblastic leukemia.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Initial Dose Level Decitabine 15 mg/m2/day given IV over 1 hour on days 1 through 7 and days 15 through 21. Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 3 through 10 and days 17 through 24 |
Drug: Decitabine
10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19.
Other Names:
Drug: Vorinostat
180 mg/m2/day (Max dose=400mg daily) given orally on days 2 through 7 and days 16 through 21.
Other Names:
Drug: Vincristine
1.5 mg/m2/day (Max dose 2 mg) given IV push on days 10, 17, 24 and 31.
Other Names:
Drug: Dexamethasone
20 mg/m2/day divided BID given orally on days 8 through 12 and 22 through 26.
Other Names:
Drug: Mitoxantrone
10 mg/m2/day given on days 8 and 9 as a short IV infusion over 5-15 minutes; do not infuse over less than 3 minutes
Other Names:
Drug: Pegaspargase
2500 international units/m2/day IM or IV on days 10 and 24.
Other Names:
Drug: Methotrexate
Given intrathecally to all patients the dose defined by age below.
8 mg for patients age 1-1.99
10 mg for patients age 2-2.99
12 mg for patients 3-8.99 years of age
15 mg for patients >9 years of age
CNS 1 or 2 patients get doses on day 8, 22 and 35 and CNS 3 patients should get doses on day 8, 15, 22, 29 and 35
Other Names:
|
| Experimental: Modified Dose Level Decitabine 10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19. Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 2 through 7 and days 16 through 21 |
Drug: Decitabine
10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19.
Other Names:
Drug: Vorinostat
180 mg/m2/day (Max dose=400mg daily) given orally on days 2 through 7 and days 16 through 21.
Other Names:
Drug: Vincristine
1.5 mg/m2/day (Max dose 2 mg) given IV push on days 10, 17, 24 and 31.
Other Names:
Drug: Dexamethasone
20 mg/m2/day divided BID given orally on days 8 through 12 and 22 through 26.
Other Names:
Drug: Mitoxantrone
10 mg/m2/day given on days 8 and 9 as a short IV infusion over 5-15 minutes; do not infuse over less than 3 minutes
Other Names:
Drug: Pegaspargase
2500 international units/m2/day IM or IV on days 10 and 24.
Other Names:
Drug: Methotrexate
Given intrathecally to all patients the dose defined by age below.
8 mg for patients age 1-1.99
10 mg for patients age 2-2.99
12 mg for patients 3-8.99 years of age
15 mg for patients >9 years of age
CNS 1 or 2 patients get doses on day 8, 22 and 35 and CNS 3 patients should get doses on day 8, 15, 22, 29 and 35
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants Who Experienced a Dose Limiting Toxicity (DLT). [6 weeks]
To evaluate the side effects of giving decitabine and vorinostat before and during chemotherapy using the standard drugs vincristine, dexamethasone, PEG-asparaginase and mitoxantrone.
Secondary Outcome Measures
- Disease Response Rate After Treatment. [6 weeks]
Bone marrow evaluation was performed on Day 35 of study to evaluate treatment response. CR defined as attaining M1 marrow (<5% blasts) with no evidence of circulating blasts or extramedullary disease in addition to recovery of peripheral blood counts (ANC >750/uL and platelet count >75,000/uL). CRp was defined as attaining an M1 marrow with no evidence of circulating blasts or extramedullary disease in addition to recovery of ANC but insufficient recovery of platelets. CRi was attaining M1 marrow with no evidence of circulating blasts or extramedullary disease but insufficient recovery of ANC with or without sufficient recovery of platelets. PR was defined as no evidence of circulating blasts and achievement of M2 marrow (5-25% blasts) without new sites of disease and with recovery of ANC. SD is for patients who did not meet the criteria for PR, CR, CRp, or CRi. PD is an increase of at least 25% in the absolute number of leukemia cells or development of new sites.
Eligibility Criteria
Criteria
Inclusion Criteria:
- Patients must be ≥1 and ≤ 21 years of age when originally diagnosed with ALL.
Diagnosis
-
Patients must have a diagnosis of acute lymphoblastic leukemia (ALL) with ≥ 25% blasts in the bone marrow (M3), with or without extramedullary disease.
-
Patients may have CNS 1, 2 or 3 disease.
-
Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for patients ≤ 16 years of age.
-
Prior Therapy
-
Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
-
Patients must have had 2 or more prior therapeutic attempts defined as:
-
Relapse after going into remission from re-induction for the first or subsequent relapse (ie: 2nd , 3rd, 4th…relapse), OR
-
Refractory disease after first or greater relapse and a re-induction attempt, OR
-
Failing to go into remission from original diagnosis after 2 previous induction attempts.
-
Hematopoietic Stem Cell Transplant: Patients who have experienced their relapse after a HSCT are eligible, provided they have no evidence of Graft-versus-Host Disease (GVHD) and are at least 60 days post-transplant at the time of enrollment.
-
Prior anthracycline exposure: Patients must have less than 400 mg/m2 lifetime exposure of anthracycline chemotherapy. (See Appendix II for calculation worksheet)
-
Hematopoietic grow factors: It must have been at least 7 days since the completion of therapy with GCSF or other growth factors at the time of enrollment. It must have been at least 14 days since the completion of therapy with pegfilgrastim (Neulasta®).
-
Biologic (anti-neoplastic) therapy: It must be at least 7 days after last does of biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair
-
Monoclonal antibodies: At least 3 half-lives of the antibody must have elapsed after the last dose of monoclonal antibody. (ie. Rituximab=66 days, Epratuzumab=69 days)
-
Immunotherapy: At least 42 days after the completion of any type of immunotherapy, e.g. tumor vaccines.
Renal and Hepatic Function
-
Patient's serum creatinine must be ≤ 1.5 x institutional upper limit of normal (ULN) according to age. If the serum creatinine is greater than 1.5 times normal, the patient must have a calculated creatinine clearance or radioisotope GRF ≥ 70mL/min/1.73m2.
-
Patient's ALT and AST must be < 5 x institutional upper limit of norm ULN. The hepatic requirements are waived for patients with known or suspected liver involvement who would otherwise be eligible after consultation with the Study Chair or Vice Chair.
-
Patient's total bilirubin must be ≤ 1.5 x ULN. The hepatic requirements are waived for patients with known or suspected liver involvement who would otherwise be eligible.
Cardiac Function:
- Patient must have a shortening fraction ≥ 27% by Echo or an ejection fraction ≥ 50% by MUGA.
Reproductive Function
-
Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed prior to enrollment.
-
Female patients with infants must agree not to breastfeed their infants while on this study.
-
Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study.
Exclusion Criteria:
-
Patients will be excluded if they are receiving Valproic Acid (VPA) therapy.
-
Patients will be excluded if they have a known allergy to any of the drugs used in the study.
-
Patients will be excluded if they have a systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment.
-
Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period.
-
Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results.
-
Patients will be excluded if they have had any positive fungal culture in the last 30 days prior to enrollment.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Childrens Hospital Los Angeles | Los Angeles | California | United States | 90027 |
| 2 | CHOC | Orange | California | United States | |
| 3 | UCSF School of Medicine | San Francisco | California | United States | 94143-0106 |
| 4 | The Children's Hospital, University of Colorado | Aurora | Colorado | United States | 80045 |
| 5 | Children's National Medical Center | Washington | District of Columbia | United States | |
| 6 | University of Miami Cancer Center | Miami | Florida | United States | 33136 |
| 7 | Children's Healthcare of Atlanta, Emory University | Atlanta | Georgia | United States | |
| 8 | Lurie Children's Hospital | Chicago | Illinois | United States | |
| 9 | Johns Hopkins University | Baltimore | Maryland | United States | |
| 10 | Dana Farber | Boston | Massachusetts | United States | |
| 11 | C.S. Mott Children's Hospital | Ann Arbor | Michigan | United States | 48109-0914 |
| 12 | Childrens Hospital & Clinics of Minnesota | Minneapolis | Minnesota | United States | 55404-4597 |
| 13 | University of Minnesota Children's Hospital | Minneapolis | Minnesota | United States | |
| 14 | Children's Mercy Hospitals and Clinics | Kansas City | Missouri | United States | 64108 |
| 15 | New York University Medical Center | New York | New York | United States | 10016 |
| 16 | Children's Hospital New York-Presbyterian | New York | New York | United States | 10032 |
| 17 | Levine Children's Hospital at Carolinas Medical Center | Charlotte | North Carolina | United States | 28203 |
| 18 | Nationwide Childrens Hospital | Columbus | Ohio | United States | |
| 19 | Oregon Health and Science University | Portland | Oregon | United States | |
| 20 | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania | United States | 19104 |
| 21 | St. Jude | Memphis | Tennessee | United States | 38105-3678 |
| 22 | Vanderbilt Children's Hospital | Nashville | Tennessee | United States | |
| 23 | University of Texas at Southwestern | Dallas | Texas | United States | |
| 24 | Cook Children's Medical Center | Fort Worth | Texas | United States | 76104 |
| 25 | Seattle Children's Hospital | Seattle | Washington | United States | 98105 |
| 26 | Children's Hospital at Westmead | Westmead | New South Wales | Australia | |
| 27 | Royal Children's Hospital | Brisbane | Queensland | Australia | |
| 28 | Sydney Children's Hospital | Sydney | Australia |
Sponsors and Collaborators
- Therapeutic Advances in Childhood Leukemia Consortium
Investigators
- Study Chair: Michael Burke, MD, Medical College of Wisconsin
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- T2009-003
Study Results
Participant Flow
| Recruitment Details | This is a pilot study where 16 patients are anticipated to be enrolled. Anticipated enrollment will take 2.5 years. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Initial Dose Level | Modified Dose Level |
|---|---|---|
| Arm/Group Description | Decitabine 15 mg/m2/day given IV over 1 hour on days 1 through 7 and days 15 through 21. Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 3 through 10 and days 17 through 24 | Decitabine 10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19. Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 2 through 7 and days 16 through 21 |
| Period Title: Overall Study | ||
| STARTED | 5 | 18 |
| COMPLETED | 3 | 13 |
| NOT COMPLETED | 2 | 5 |
Baseline Characteristics
| Arm/Group Title | Initial Dose Level | Modified Dose Level | Total |
|---|---|---|---|
| Arm/Group Description | Decitabine 15 mg/m2/day given IV over 1 hour on days 1 through 7 and days 15 through 21. Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 3 through 10 and days 17 through 24 | Decitabine 10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19. Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 2 through 7 and days 16 through 21 | Total of all reporting groups |
| Overall Participants | 5 | 18 | 23 |
| Age (years) [Median (Full Range) ] | |||
| Median (Full Range) [years] |
12.5
|
12.0
|
12.0
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
2
40%
|
4
22.2%
|
6
26.1%
|
| Male |
3
60%
|
14
77.8%
|
17
73.9%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
3
60%
|
9
50%
|
12
52.2%
|
| Not Hispanic or Latino |
2
40%
|
9
50%
|
11
47.8%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
0
0%
|
1
5.6%
|
1
4.3%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
0
0%
|
2
11.1%
|
2
8.7%
|
| White |
5
100%
|
10
55.6%
|
15
65.2%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
5
27.8%
|
5
21.7%
|
| CNS Status (Count of Participants) | |||
| CNS 1 |
4
80%
|
14
77.8%
|
18
78.3%
|
| CNS 2 |
1
20%
|
2
11.1%
|
3
13%
|
| CNS 3 |
0
0%
|
2
11.1%
|
2
8.7%
|
| Prior hematopoietic cell transplantation (HCT) (Count of Participants) | |||
| Yes had prior HCT |
3
60%
|
8
44.4%
|
11
47.8%
|
| No did not have prior HCT |
2
40%
|
10
55.6%
|
12
52.2%
|
| Relapse # at enrollment (Count of Participants) | |||
| 2nd Relapse |
2
40%
|
13
72.2%
|
15
65.2%
|
| 3rd Relapse |
1
20%
|
1
5.6%
|
2
8.7%
|
| Refractory |
2
40%
|
4
22.2%
|
6
26.1%
|
Outcome Measures
| Title | Number of Participants Who Experienced a Dose Limiting Toxicity (DLT). |
|---|---|
| Description | To evaluate the side effects of giving decitabine and vorinostat before and during chemotherapy using the standard drugs vincristine, dexamethasone, PEG-asparaginase and mitoxantrone. |
| Time Frame | 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who entered the study. |
| Arm/Group Title | Initial Dose Level | Modified Dose Level |
|---|---|---|
| Arm/Group Description | Decitabine 15 mg/m2/day given IV over 1 hour on days 1 through 7 and days 15 through 21. Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 3 through 10 and days 17 through 24 | Decitabine 10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19. Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 2 through 7 and days 16 through 21 |
| Measure Participants | 5 | 18 |
| # of patients with DLT |
2
40%
|
1
5.6%
|
| # of patients without DLT |
2
40%
|
12
66.7%
|
| # of patients not evaluable |
1
20%
|
5
27.8%
|
| Title | Disease Response Rate After Treatment. |
|---|---|
| Description | Bone marrow evaluation was performed on Day 35 of study to evaluate treatment response. CR defined as attaining M1 marrow (<5% blasts) with no evidence of circulating blasts or extramedullary disease in addition to recovery of peripheral blood counts (ANC >750/uL and platelet count >75,000/uL). CRp was defined as attaining an M1 marrow with no evidence of circulating blasts or extramedullary disease in addition to recovery of ANC but insufficient recovery of platelets. CRi was attaining M1 marrow with no evidence of circulating blasts or extramedullary disease but insufficient recovery of ANC with or without sufficient recovery of platelets. PR was defined as no evidence of circulating blasts and achievement of M2 marrow (5-25% blasts) without new sites of disease and with recovery of ANC. SD is for patients who did not meet the criteria for PR, CR, CRp, or CRi. PD is an increase of at least 25% in the absolute number of leukemia cells or development of new sites. |
| Time Frame | 6 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| Patients who entered the study. |
| Arm/Group Title | Initial Dose Level | Modified Dose Level |
|---|---|---|
| Arm/Group Description | Decitabine 15 mg/m2/day given IV over 1 hour on days 1 through 7 and days 15 through 21. Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 3 through 10 and days 17 through 24 | Decitabine 10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19. Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 2 through 7 and days 16 through 21 |
| Measure Participants | 5 | 18 |
| complete response (CR) |
0
0%
|
1
5.6%
|
| complete response without platelet recovery (CRp) |
1
20%
|
3
16.7%
|
| complete remission with incomplete recovery (CRi) |
1
20%
|
3
16.7%
|
| stable disease (SD) |
1
20%
|
4
22.2%
|
| patient not evaluable for response |
2
40%
|
7
38.9%
|
Adverse Events
| Time Frame | Adverse events and suspected adverse reactions will be collected and reported on the electronic case report forms beginning with the first dose of decitabine and vorinostat until 30 days following last dose of decitabine and vorinostat. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | The definition of adverse event and/or serious adverse event used to collect adverse event information is the same from clinicaltrials.gov definitions. | |||
| Arm/Group Title | Initial Dose Level | Modified Dose Level | ||
| Arm/Group Description | Decitabine 15 mg/m2/day given IV over 1 hour on days 1 through 7 and days 15 through 21. Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 3 through 10 and days 17 through 24 | Decitabine 10 mg/m2/day given IV over 1 hour on days 1 through 5 and days 15 through 19. Vorinostat: 180 mg/m2/day (Max dose=400 mg daily) given orally on days 2 through 7 and days 16 through 21 | ||
All Cause Mortality |
||||
| Initial Dose Level | Modified Dose Level | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/5 (100%) | 13/18 (72.2%) | ||
Serious Adverse Events |
||||
| Initial Dose Level | Modified Dose Level | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/5 (100%) | 18/18 (100%) | ||
| Blood and lymphatic system disorders | ||||
| neutrophil count decrease | 2/5 (40%) | 5/18 (27.8%) | ||
| platelet count decreased | 2/5 (40%) | 7/18 (38.9%) | ||
| white blood cell decreased | 2/5 (40%) | 6/18 (33.3%) | ||
| Bone marrow hypocellular | 1/5 (20%) | 0/18 (0%) | ||
| Capillary leak syndrome | 1/5 (20%) | 0/18 (0%) | ||
| Cardiac disorders | ||||
| Hypotension | 0/5 (0%) | 2/18 (11.1%) | ||
| Left ventricular systolic dysfunction | 1/5 (20%) | 1/18 (5.6%) | ||
| sinus bradycardia | 0/5 (0%) | 2/18 (11.1%) | ||
| Right ventricular dysfunction | 1/5 (20%) | 0/18 (0%) | ||
| Endocrine disorders | ||||
| Acute kidney injury | 0/5 (0%) | 2/18 (11.1%) | ||
| Gastrointestinal disorders | ||||
| Gastrointestinal disorder - Other | 1/5 (20%) | 0/18 (0%) | ||
| General disorders | ||||
| Somnolence | 1/5 (20%) | 0/18 (0%) | ||
| Infections and infestations | ||||
| Ano-rectal infection | 0/5 (0%) | 1/18 (5.6%) | ||
| Lung infection | 0/5 (0%) | 1/18 (5.6%) | ||
| sepsis | 2/5 (40%) | 4/18 (22.2%) | ||
| soft tissue infection | 0/5 (0%) | 1/18 (5.6%) | ||
| Metabolism and nutrition disorders | ||||
| Anemia | 1/5 (20%) | 11/18 (61.1%) | ||
| Acidosis | 0/5 (0%) | 2/18 (11.1%) | ||
| Alanine aminotransferase increase | 0/5 (0%) | 2/18 (11.1%) | ||
| Alkaline phosphatase increased | 0/5 (0%) | 3/18 (16.7%) | ||
| Blood bilirubin increased | 1/5 (20%) | 2/18 (11.1%) | ||
| GGT increased | 0/5 (0%) | 1/18 (5.6%) | ||
| Hypercalcemia | 0/5 (0%) | 1/18 (5.6%) | ||
| Hyperglycemia | 1/5 (20%) | 1/18 (5.6%) | ||
| Hyperkalemia | 0/5 (0%) | 1/18 (5.6%) | ||
| Hypermagnesemia | 0/5 (0%) | 1/18 (5.6%) | ||
| Hypernatermia | 1/5 (20%) | 1/18 (5.6%) | ||
| Hypertriglyceridemia | 1/5 (20%) | 1/18 (5.6%) | ||
| Hyperuricemia | 0/5 (0%) | 1/18 (5.6%) | ||
| Hypocalcemia | 0/5 (0%) | 1/18 (5.6%) | ||
| Hypokalemia | 2/5 (40%) | 9/18 (50%) | ||
| Hypophosphatemia | 0/5 (0%) | 2/18 (11.1%) | ||
| Lipase increased | 1/5 (20%) | 2/18 (11.1%) | ||
| Lymphocyte count decreased | 2/5 (40%) | 2/18 (11.1%) | ||
| Lymphocyte count increased | 0/5 (0%) | 1/18 (5.6%) | ||
| serum amylase increased | 0/5 (0%) | 1/18 (5.6%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Agitation | 0/5 (0%) | 1/18 (5.6%) | ||
| Nervous system disorders | ||||
| Encephalopathy | 0/5 (0%) | 1/18 (5.6%) | ||
| nervous system disorder - other | 0/5 (0%) | 1/18 (5.6%) | ||
| Altered mental status | 0/5 (0%) | 1/18 (5.6%) | ||
| Reversible posterior leukoencephalopathy syndrome | 0/5 (0%) | 1/18 (5.6%) | ||
| Seizure | 1/5 (20%) | 0/18 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Adult respiratory distress syndrome | 1/5 (20%) | 1/18 (5.6%) | ||
| Hypoxia | 0/5 (0%) | 2/18 (11.1%) | ||
| Pleural effusion | 0/5 (0%) | 1/18 (5.6%) | ||
| Pulmonary edema | 0/5 (0%) | 2/18 (11.1%) | ||
| respiratory failure | 1/5 (20%) | 2/18 (11.1%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Initial Dose Level | Modified Dose Level | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/5 (100%) | 18/18 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 1/5 (20%) | 15/18 (83.3%) | ||
| Blood bilirubin increased | 1/5 (20%) | 5/18 (27.8%) | ||
| Tumor lysis syndrome | 1/5 (20%) | 1/18 (5.6%) | ||
| White blood cell decreased | 0/5 (0%) | 1/18 (5.6%) | ||
| Cardiac disorders | ||||
| Hypertension | 2/5 (40%) | 3/18 (16.7%) | ||
| Hypotension | 1/5 (20%) | 2/18 (11.1%) | ||
| Left ventricular systolic dysfunction | 0/5 (0%) | 1/18 (5.6%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 3/5 (60%) | 0/18 (0%) | ||
| Ascites | 0/5 (0%) | 1/18 (5.6%) | ||
| Colitis | 1/5 (20%) | 0/18 (0%) | ||
| Diarrhea | 1/5 (20%) | 2/18 (11.1%) | ||
| Gastric hemorrhage | 0/5 (0%) | 2/18 (11.1%) | ||
| Hepatobiliary disorders - Other | 1/5 (20%) | 0/18 (0%) | ||
| Ileus | 0/5 (0%) | 1/18 (5.6%) | ||
| Lower gastrointestinal hemorrhage | 1/5 (20%) | 1/18 (5.6%) | ||
| Pancreatitis | 1/5 (20%) | 3/18 (16.7%) | ||
| Rectal hemorrhage | 0/5 (0%) | 1/18 (5.6%) | ||
| General disorders | ||||
| Anorexia | 2/5 (40%) | 4/18 (22.2%) | ||
| Dehydration | 1/5 (20%) | 1/18 (5.6%) | ||
| Delirium | 1/5 (20%) | 1/18 (5.6%) | ||
| Depressed level of consciousness | 0/5 (0%) | 1/18 (5.6%) | ||
| Dizziness | 0/5 (0%) | 1/18 (5.6%) | ||
| Dyspnea | 0/5 (0%) | 1/18 (5.6%) | ||
| Epistaxis | 0/5 (0%) | 1/18 (5.6%) | ||
| Fever | 1/5 (20%) | 0/18 (0%) | ||
| Generalized muscle weakness | 1/5 (20%) | 2/18 (11.1%) | ||
| Hypoxia | 1/5 (20%) | 3/18 (16.7%) | ||
| Lethargy | 1/5 (20%) | 0/18 (0%) | ||
| Malaise | 0/5 (0%) | 1/18 (5.6%) | ||
| Muscle weakness | 0/5 (0%) | 1/18 (5.6%) | ||
| Nausea | 1/5 (20%) | 2/18 (11.1%) | ||
| Pain in extremity | 0/5 (0%) | 2/18 (11.1%) | ||
| Weight loss | 0/5 (0%) | 2/18 (11.1%) | ||
| Infections and infestations | ||||
| Catheter related infection | 1/5 (20%) | 3/18 (16.7%) | ||
| Enterocolitis infectious | 0/5 (0%) | 2/18 (11.1%) | ||
| Febrile neutropenia | 2/5 (40%) | 15/18 (83.3%) | ||
| Infective myositis | 1/5 (20%) | 0/18 (0%) | ||
| Lip infection | 0/5 (0%) | 1/18 (5.6%) | ||
| Lung infection | 1/5 (20%) | 4/18 (22.2%) | ||
| Lymph gland infection | 0/5 (0%) | 1/18 (5.6%) | ||
| Mucosal infection | 1/5 (20%) | 2/18 (11.1%) | ||
| Scrotal infection | 0/5 (0%) | 1/18 (5.6%) | ||
| Skin infection | 0/5 (0%) | 2/18 (11.1%) | ||
| Soft tissue infection | 0/5 (0%) | 3/18 (16.7%) | ||
| Typhlitis | 0/5 (0%) | 2/18 (11.1%) | ||
| Coagulase negative staphylococus | 1/5 (20%) | 0/18 (0%) | ||
| Enterococcus Faecalis | 2/5 (40%) | 0/18 (0%) | ||
| Candida Kruseli | 3/5 (60%) | 0/18 (0%) | ||
| Klebsiella pneumonae | 0/5 (0%) | 1/18 (5.6%) | ||
| Candida parapsilosis | 0/5 (0%) | 1/18 (5.6%) | ||
| Pseudomonas aeruginosa | 0/5 (0%) | 1/18 (5.6%) | ||
| Necrotizing fascitis | 0/5 (0%) | 1/18 (5.6%) | ||
| Bipolaris spicifera | 0/5 (0%) | 1/18 (5.6%) | ||
| Investigations | ||||
| Investigations - Other | 1/5 (20%) | 0/18 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Acidosis | 0/5 (0%) | 1/18 (5.6%) | ||
| Alanine aminotransferase increased | 1/5 (20%) | 3/18 (16.7%) | ||
| Alkaline phosphatase increased | 0/5 (0%) | 1/18 (5.6%) | ||
| Aspartate aminotransferase increased | 1/5 (20%) | 4/18 (22.2%) | ||
| Cholesterol high | 0/5 (0%) | 1/18 (5.6%) | ||
| Creatinine increased | 0/5 (0%) | 2/18 (11.1%) | ||
| Gamma-glutamyl transferase increased | 1/5 (20%) | 0/18 (0%) | ||
| Hyperglycemia | 2/5 (40%) | 3/18 (16.7%) | ||
| Hypercalcemia | 0/5 (0%) | 1/18 (5.6%) | ||
| Hyperkalemia | 0/5 (0%) | 1/18 (5.6%) | ||
| Hypermagnesemia | 1/5 (20%) | 0/18 (0%) | ||
| Hypertriglyceridemia | 1/5 (20%) | 0/18 (0%) | ||
| Hypoalbuminemia | 2/5 (40%) | 2/18 (11.1%) | ||
| Hypocalcemia | 2/5 (40%) | 5/18 (27.8%) | ||
| Hypoglycemia | 2/5 (40%) | 0/18 (0%) | ||
| Hypokalemia | 2/5 (40%) | 5/18 (27.8%) | ||
| Hypomagnesemia | 1/5 (20%) | 0/18 (0%) | ||
| Hyponatremia | 2/5 (40%) | 5/18 (27.8%) | ||
| Hypophosphatemia | 1/5 (20%) | 6/18 (33.3%) | ||
| Iron overload | 0/5 (0%) | 1/18 (5.6%) | ||
| Lymphocyte count decreased | 0/5 (0%) | 3/18 (16.7%) | ||
| Lymphocyte count increased | 0/5 (0%) | 1/18 (5.6%) | ||
| Hyperammonemia | 0/5 (0%) | 1/18 (5.6%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Back pain | 1/5 (20%) | 1/18 (5.6%) | ||
| Bone pain | 0/5 (0%) | 1/18 (5.6%) | ||
| Nervous system disorders | ||||
| Spasticity | 0/5 (0%) | 1/18 (5.6%) | ||
| Syncope | 0/5 (0%) | 1/18 (5.6%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Bronchopulmonary hemorrhage | 1/5 (20%) | 0/18 (0%) | ||
| Pleuritic pain | 0/5 (0%) | 1/18 (5.6%) | ||
| Pneumonitis | 0/5 (0%) | 2/18 (11.1%) | ||
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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Clinical Research Coordinator, Consortia |
|---|---|
| Organization | Therapeutic Advancements of Childhood Leukemia and Lymphoma |
| Phone | 323-361-5312 |
| rleong@chla.usc.edu |
- T2009-003