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A Pilot Study of Decitabine and Vorinostat With Chemotherapy for Relapsed ALL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01483690
Recruitment Status : Terminated (Toxicity)
First Posted : December 1, 2011
Results First Posted : October 27, 2020
Last Update Posted : October 27, 2020
Sponsor:
Information provided by (Responsible Party):
Therapeutic Advances in Childhood Leukemia Consortium

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Acute Lymphoblastic Leukemia
Precursor B-Cell Lymphoblastic Leukemia
Precursor T-Cell Lymphoblastic Leukemia
Interventions Drug: Decitabine
Drug: Vorinostat
Drug: Vincristine
Drug: Dexamethasone
Drug: Mitoxantrone
Drug: Pegaspargase
Drug: Methotrexate
Enrollment 23
Recruitment Details This is a pilot study where 16 patients are anticipated to be enrolled. Anticipated enrollment will take 2.5 years.
Pre-assignment Details  
Arm/Group Title Initial Dose Level Modified Dose Level
Hide 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
Reason Not Completed
Adverse Event             1             2
clinical deterioration             1             0
Physician Decision             0             2
exclusionary procedure             0             1
Arm/Group Title Initial Dose Level Modified Dose Level Total
Hide 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 Number of Baseline Participants 5 18 23
Hide Baseline Analysis Population Description
Total number of participants enrolled into the study.
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 5 participants 18 participants 23 participants
12.5
(4.9 to 14.5)
12.0
(1.6 to 21.4)
12.0
(1.6 to 21.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 18 participants 23 participants
Female
2
  40.0%
4
  22.2%
6
  26.1%
Male
3
  60.0%
14
  77.8%
17
  73.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 18 participants 23 participants
Hispanic or Latino
3
  60.0%
9
  50.0%
12
  52.2%
Not Hispanic or Latino
2
  40.0%
9
  50.0%
11
  47.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 18 participants 23 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
   5.6%
1
   4.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
2
  11.1%
2
   8.7%
White
5
 100.0%
10
  55.6%
15
  65.2%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
5
  27.8%
5
  21.7%
CNS Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 18 participants 23 participants
CNS 1
4
  80.0%
14
  77.8%
18
  78.3%
CNS 2
1
  20.0%
2
  11.1%
3
  13.0%
CNS 3
0
   0.0%
2
  11.1%
2
   8.7%
[1]
Measure Description:

Central nervous system (CNS) disease is divided into the following:

CNS 1 - no evidence of leukemia cerebral spinal fluid (CSF)(best outcome) CNS 2 - <5 WBC in CSF with blasts present CNS 3 - > or = 5 WBC in CSF with blasts present (worse outcome).

Prior hematopoietic cell transplantation (HCT)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 18 participants 23 participants
Yes had prior HCT
3
  60.0%
8
  44.4%
11
  47.8%
No did not have prior HCT
2
  40.0%
10
  55.6%
12
  52.2%
Relapse # at enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 18 participants 23 participants
2nd Relapse
2
  40.0%
13
  72.2%
15
  65.2%
3rd Relapse
1
  20.0%
1
   5.6%
2
   8.7%
Refractory
2
  40.0%
4
  22.2%
6
  26.1%
1.Primary Outcome
Title Number of Participants Who Experienced a Dose Limiting Toxicity (DLT).
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who entered the study.
Arm/Group Title Initial Dose Level Modified Dose Level
Hide 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

Overall Number of Participants Analyzed 5 18
Measure Type: Count of Participants
Unit of Measure: Participants
# of patients with DLT
2
  40.0%
1
   5.6%
# of patients without DLT
2
  40.0%
12
  66.7%
# of patients not evaluable
1
  20.0%
5
  27.8%
2.Secondary Outcome
Title Disease Response Rate After Treatment.
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who entered the study.
Arm/Group Title Initial Dose Level Modified Dose Level
Hide 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

Overall Number of Participants Analyzed 5 18
Measure Type: Count of Participants
Unit of Measure: Participants
complete response (CR)
0
   0.0%
1
   5.6%
complete response without platelet recovery (CRp)
1
  20.0%
3
  16.7%
complete remission with incomplete recovery (CRi)
1
  20.0%
3
  16.7%
stable disease (SD)
1
  20.0%
4
  22.2%
patient not evaluable for response
2
  40.0%
7
  38.9%
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
Hide 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 (%) Affected / at Risk (%)
Total   5/5 (100.00%)   13/18 (72.22%) 
Hide Serious Adverse Events
Initial Dose Level Modified Dose Level
Affected / at Risk (%) Affected / at Risk (%)
Total   5/5 (100.00%)   18/18 (100.00%) 
Blood and lymphatic system disorders     
neutrophil count decrease  2  2/5 (40.00%)  5/18 (27.78%) 
platelet count decreased  2  2/5 (40.00%)  7/18 (38.89%) 
white blood cell decreased  2  2/5 (40.00%)  6/18 (33.33%) 
Bone marrow hypocellular  1  1/5 (20.00%)  0/18 (0.00%) 
Capillary leak syndrome  2  1/5 (20.00%)  0/18 (0.00%) 
Cardiac disorders     
Hypotension  2  0/5 (0.00%)  2/18 (11.11%) 
Left ventricular systolic dysfunction  2  1/5 (20.00%)  1/18 (5.56%) 
sinus bradycardia  2  0/5 (0.00%)  2/18 (11.11%) 
Right ventricular dysfunction  1  1/5 (20.00%)  0/18 (0.00%) 
Endocrine disorders     
Acute kidney injury  2  0/5 (0.00%)  2/18 (11.11%) 
Gastrointestinal disorders     
Gastrointestinal disorder - Other  2  1/5 (20.00%)  0/18 (0.00%) 
General disorders     
Somnolence  2  1/5 (20.00%)  0/18 (0.00%) 
Infections and infestations     
Ano-rectal infection  2  0/5 (0.00%)  1/18 (5.56%) 
Lung infection  2  0/5 (0.00%)  1/18 (5.56%) 
sepsis  2  2/5 (40.00%)  4/18 (22.22%) 
soft tissue infection  2  0/5 (0.00%)  1/18 (5.56%) 
Metabolism and nutrition disorders     
Anemia  1  1/5 (20.00%)  11/18 (61.11%) 
Acidosis  2  0/5 (0.00%)  2/18 (11.11%) 
Alanine aminotransferase increase  2  0/5 (0.00%)  2/18 (11.11%) 
Alkaline phosphatase increased  2  0/5 (0.00%)  3/18 (16.67%) 
Blood bilirubin increased  2  1/5 (20.00%)  2/18 (11.11%) 
GGT increased  2  0/5 (0.00%)  1/18 (5.56%) 
Hypercalcemia  2  0/5 (0.00%)  1/18 (5.56%) 
Hyperglycemia  2  1/5 (20.00%)  1/18 (5.56%) 
Hyperkalemia  2  0/5 (0.00%)  1/18 (5.56%) 
Hypermagnesemia  2  0/5 (0.00%)  1/18 (5.56%) 
Hypernatermia  2  1/5 (20.00%)  1/18 (5.56%) 
Hypertriglyceridemia  2  1/5 (20.00%)  1/18 (5.56%) 
Hyperuricemia  2  0/5 (0.00%)  1/18 (5.56%) 
Hypocalcemia  2  0/5 (0.00%)  1/18 (5.56%) 
Hypokalemia  2  2/5 (40.00%)  9/18 (50.00%) 
Hypophosphatemia  2  0/5 (0.00%)  2/18 (11.11%) 
Lipase increased  2  1/5 (20.00%)  2/18 (11.11%) 
Lymphocyte count decreased  2  2/5 (40.00%)  2/18 (11.11%) 
Lymphocyte count increased  2  0/5 (0.00%)  1/18 (5.56%) 
serum amylase increased  2  0/5 (0.00%)  1/18 (5.56%) 
Musculoskeletal and connective tissue disorders     
Agitation  2  0/5 (0.00%)  1/18 (5.56%) 
Nervous system disorders     
Encephalopathy  2  0/5 (0.00%)  1/18 (5.56%) 
nervous system disorder - other  2  0/5 (0.00%)  1/18 (5.56%) 
Altered mental status  2  0/5 (0.00%)  1/18 (5.56%) 
Reversible posterior leukoencephalopathy syndrome  1  0/5 (0.00%)  1/18 (5.56%) 
Seizure  2  1/5 (20.00%)  0/18 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Adult respiratory distress syndrome  2  1/5 (20.00%)  1/18 (5.56%) 
Hypoxia  2  0/5 (0.00%)  2/18 (11.11%) 
Pleural effusion  2  0/5 (0.00%)  1/18 (5.56%) 
Pulmonary edema  2  0/5 (0.00%)  2/18 (11.11%) 
respiratory failure  2  1/5 (20.00%)  2/18 (11.11%) 
1
Term from vocabulary, NCI CTC version 4.0
2
Term from vocabulary, NCI CTCAE v4.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Initial Dose Level Modified Dose Level
Affected / at Risk (%) Affected / at Risk (%)
Total   5/5 (100.00%)   18/18 (100.00%) 
Blood and lymphatic system disorders     
Anemia  2  1/5 (20.00%)  15/18 (83.33%) 
Blood bilirubin increased  2  1/5 (20.00%)  5/18 (27.78%) 
Tumor lysis syndrome  2  1/5 (20.00%)  1/18 (5.56%) 
White blood cell decreased  2  0/5 (0.00%)  1/18 (5.56%) 
Cardiac disorders     
Hypertension  2  2/5 (40.00%)  3/18 (16.67%) 
Hypotension  2  1/5 (20.00%)  2/18 (11.11%) 
Left ventricular systolic dysfunction  2  0/5 (0.00%)  1/18 (5.56%) 
Gastrointestinal disorders     
Abdominal pain  1  3/5 (60.00%)  0/18 (0.00%) 
Ascites  2  0/5 (0.00%)  1/18 (5.56%) 
Colitis  2  1/5 (20.00%)  0/18 (0.00%) 
Diarrhea  2  1/5 (20.00%)  2/18 (11.11%) 
Gastric hemorrhage  2  0/5 (0.00%)  2/18 (11.11%) 
Hepatobiliary disorders - Other  2  1/5 (20.00%)  0/18 (0.00%) 
Ileus  2  0/5 (0.00%)  1/18 (5.56%) 
Lower gastrointestinal hemorrhage  2  1/5 (20.00%)  1/18 (5.56%) 
Pancreatitis  2  1/5 (20.00%)  3/18 (16.67%) 
Rectal hemorrhage  2  0/5 (0.00%)  1/18 (5.56%) 
General disorders     
Anorexia  2  2/5 (40.00%)  4/18 (22.22%) 
Dehydration  2  1/5 (20.00%)  1/18 (5.56%) 
Delirium  2  1/5 (20.00%)  1/18 (5.56%) 
Depressed level of consciousness  2  0/5 (0.00%)  1/18 (5.56%) 
Dizziness  2  0/5 (0.00%)  1/18 (5.56%) 
Dyspnea  2  0/5 (0.00%)  1/18 (5.56%) 
Epistaxis  2  0/5 (0.00%)  1/18 (5.56%) 
Fever  2  1/5 (20.00%)  0/18 (0.00%) 
Generalized muscle weakness  2  1/5 (20.00%)  2/18 (11.11%) 
Hypoxia  2  1/5 (20.00%)  3/18 (16.67%) 
Lethargy  2  1/5 (20.00%)  0/18 (0.00%) 
Malaise  2  0/5 (0.00%)  1/18 (5.56%) 
Muscle weakness  2  0/5 (0.00%)  1/18 (5.56%) 
Nausea  2  1/5 (20.00%)  2/18 (11.11%) 
Pain in extremity  2  0/5 (0.00%)  2/18 (11.11%) 
Weight loss  2  0/5 (0.00%)  2/18 (11.11%) 
Infections and infestations     
Catheter related infection  2  1/5 (20.00%)  3/18 (16.67%) 
Enterocolitis infectious  2  0/5 (0.00%)  2/18 (11.11%) 
Febrile neutropenia  2  2/5 (40.00%)  15/18 (83.33%) 
Infective myositis  2  1/5 (20.00%)  0/18 (0.00%) 
Lip infection  2  0/5 (0.00%)  1/18 (5.56%) 
Lung infection  2  1/5 (20.00%)  4/18 (22.22%) 
Lymph gland infection  2  0/5 (0.00%)  1/18 (5.56%) 
Mucosal infection  2  1/5 (20.00%)  2/18 (11.11%) 
Scrotal infection  2  0/5 (0.00%)  1/18 (5.56%) 
Skin infection  2  0/5 (0.00%)  2/18 (11.11%) 
Soft tissue infection  2  0/5 (0.00%)  3/18 (16.67%) 
Typhlitis  2  0/5 (0.00%)  2/18 (11.11%) 
Coagulase negative staphylococus  1  1/5 (20.00%)  0/18 (0.00%) 
Enterococcus Faecalis  2  2/5 (40.00%)  0/18 (0.00%) 
Candida Kruseli  2  3/5 (60.00%)  0/18 (0.00%) 
Klebsiella pneumonae  2  0/5 (0.00%)  1/18 (5.56%) 
Candida parapsilosis  1  0/5 (0.00%)  1/18 (5.56%) 
Pseudomonas aeruginosa  2  0/5 (0.00%)  1/18 (5.56%) 
Necrotizing fascitis  2  0/5 (0.00%)  1/18 (5.56%) 
Bipolaris spicifera  2  0/5 (0.00%)  1/18 (5.56%) 
Investigations     
Investigations - Other  2  1/5 (20.00%)  0/18 (0.00%) 
Metabolism and nutrition disorders     
Acidosis  2  0/5 (0.00%)  1/18 (5.56%) 
Alanine aminotransferase increased  2  1/5 (20.00%)  3/18 (16.67%) 
Alkaline phosphatase increased  2  0/5 (0.00%)  1/18 (5.56%) 
Aspartate aminotransferase increased  2  1/5 (20.00%)  4/18 (22.22%) 
Cholesterol high  2  0/5 (0.00%)  1/18 (5.56%) 
Creatinine increased  2  0/5 (0.00%)  2/18 (11.11%) 
Gamma-glutamyl transferase increased  2  1/5 (20.00%)  0/18 (0.00%) 
Hyperglycemia  2  2/5 (40.00%)  3/18 (16.67%) 
Hypercalcemia  2  0/5 (0.00%)  1/18 (5.56%) 
Hyperkalemia  2  0/5 (0.00%)  1/18 (5.56%) 
Hypermagnesemia  2  1/5 (20.00%)  0/18 (0.00%) 
Hypertriglyceridemia  2  1/5 (20.00%)  0/18 (0.00%) 
Hypoalbuminemia  2  2/5 (40.00%)  2/18 (11.11%) 
Hypocalcemia  2  2/5 (40.00%)  5/18 (27.78%) 
Hypoglycemia  2  2/5 (40.00%)  0/18 (0.00%) 
Hypokalemia  2  2/5 (40.00%)  5/18 (27.78%) 
Hypomagnesemia  1  1/5 (20.00%)  0/18 (0.00%) 
Hyponatremia  2  2/5 (40.00%)  5/18 (27.78%) 
Hypophosphatemia  2  1/5 (20.00%)  6/18 (33.33%) 
Iron overload  2  0/5 (0.00%)  1/18 (5.56%) 
Lymphocyte count decreased  2  0/5 (0.00%)  3/18 (16.67%) 
Lymphocyte count increased  2  0/5 (0.00%)  1/18 (5.56%) 
Hyperammonemia  1  0/5 (0.00%)  1/18 (5.56%) 
Musculoskeletal and connective tissue disorders     
Back pain  2  1/5 (20.00%)  1/18 (5.56%) 
Bone pain  2  0/5 (0.00%)  1/18 (5.56%) 
Nervous system disorders     
Spasticity  2  0/5 (0.00%)  1/18 (5.56%) 
Syncope  2  0/5 (0.00%)  1/18 (5.56%) 
Respiratory, thoracic and mediastinal disorders     
Bronchopulmonary hemorrhage  2  1/5 (20.00%)  0/18 (0.00%) 
Pleuritic pain  2  0/5 (0.00%)  1/18 (5.56%) 
Pneumonitis  1  0/5 (0.00%)  2/18 (11.11%) 
1
Term from vocabulary, NCI CTC version 4.0
2
Term from vocabulary, NCI CTCAE v4.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Research Coordinator, Consortia
Organization: Therapeutic Advancements of Childhood Leukemia and Lymphoma
Phone: 323-361-5312
EMail: rleong@chla.usc.edu
Layout table for additonal information
Responsible Party: Therapeutic Advances in Childhood Leukemia Consortium
ClinicalTrials.gov Identifier: NCT01483690    
Other Study ID Numbers: T2009-003
First Submitted: November 29, 2011
First Posted: December 1, 2011
Results First Submitted: September 8, 2020
Results First Posted: October 27, 2020
Last Update Posted: October 27, 2020