Trial Outcomes & Findings for Pre-reinductive Decitabine and Vorinostat in Relapsed Lymphoblastic Lymphoma or Acute Lymphoblastic Leukemia (NCT NCT00882206)
NCT ID: NCT00882206
Last Updated: 2017-12-28
Results Overview
Response includes both complete remission (defined as \<5% leukemic blasts in the bone marrow) and partial remission (defined as a greater than 35% reduction in the bone marrow leukemia blast percentage at day 33)
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
15 participants
Primary outcome timeframe
Day 33
Results posted on
2017-12-28
Participant Flow
Participant milestones
| Measure |
Decitabine / Vorinostat
This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy.
cytarabine: At baseline when peripheral blood draw and bone marrow aspirate performed.
\*Intrathecal Cytarabine administered dependent upon age - ranging from 30 mg to 70 mg.
decitabine: Days 1-4, 15 mg/m\^2 intravenously (IV) over 1 hour
doxorubicin hydrochloride: Day 5, 60 mg/m\^2 intravenously (IV) over 15 minutes
imatinib mesylate: 340 mg/m2 by mouth every day (rounded to the nearest 100 mg) for age \<18 years and 400 mg orally every day for \>18 years on Days 5-33.
methotrexate: \*\*Intrathecal Methotrexate administered dependent upon age - ranging from 8 mg to 15 mg.
pegaspargase: 2,500 IU/m2 IM or IV q week (days 6, 12, 19, 26)
prednisone: 40mg/m2/day divided BID (days 5 - 33)
vincristine sulfate: 1.5mg/m2 (max 2 mg) iv push q week (days 5, 12,
|
|---|---|
|
Overall Study
STARTED
|
13
|
|
Overall Study
COMPLETED
|
13
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pre-reinductive Decitabine and Vorinostat in Relapsed Lymphoblastic Lymphoma or Acute Lymphoblastic Leukemia
Baseline characteristics by cohort
| Measure |
Decitabine / Vorinostat
n=13 Participants
This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy.
|
|---|---|
|
Age, Continuous
|
16 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
13 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Day 33Population: The following participants were removed from the analysis: two patients had an early death; one patient had early disease progression; one patient was found to have nervous system involvement on day 5 of therapy; and one patient stopped study therapy due to toxicities.
Response includes both complete remission (defined as \<5% leukemic blasts in the bone marrow) and partial remission (defined as a greater than 35% reduction in the bone marrow leukemia blast percentage at day 33)
Outcome measures
| Measure |
Decitabine / Vorinostat
n=8 Participants
This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy.
|
|---|---|
|
Response to Treatment
|
6 participants
|
SECONDARY outcome
Timeframe: Day 0the percentage of methylated DNA
Outcome measures
| Measure |
Decitabine / Vorinostat
n=8 Participants
This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy.
|
|---|---|
|
Level of Methylation
|
84.98 percentage of DNA
Standard Deviation 1.48
|
SECONDARY outcome
Timeframe: Day 5Population: The following participants were removed from the analysis: two patients had an early death; one patient had early disease progression; one patient was found to have nervous system involvement on day 5 of therapy; and one patient stopped study therapy due to toxicities.
the percentage of methylated DNA
Outcome measures
| Measure |
Decitabine / Vorinostat
n=8 Participants
This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy.
|
|---|---|
|
Level of Methylation
|
79.82 percentage of DNA
Standard Deviation 3.04
|
SECONDARY outcome
Timeframe: Day 33Population: The following participants were removed from the analysis: two patients had an early death; one patient had early disease progression; one patient was found to have nervous system involvement on day 5 of therapy; and one patient stopped study therapy due to toxicities.
the percentage of methylated DNA
Outcome measures
| Measure |
Decitabine / Vorinostat
n=8 Participants
This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy.
|
|---|---|
|
Level of Methylation
|
86.1 percentage of DNA
Standard Deviation 1.87
|
Adverse Events
Decitabine / Vorinostat
Serious events: 8 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Decitabine / Vorinostat
n=13 participants at risk
This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy.
cytarabine: At baseline when peripheral blood draw and bone marrow aspirate performed.
\*Intrathecal Cytarabine administered dependent upon age - ranging from 30 mg to 70 mg.
decitabine: Days 1-4, 15 mg/m\^2 intravenously (IV) over 1 hour
doxorubicin hydrochloride: Day 5, 60 mg/m\^2 intravenously (IV) over 15 minutes
imatinib mesylate: 340 mg/m2 by mouth every day (rounded to the nearest 100 mg) for age \<18 years and 400 mg orally every day for \>18 years on Days 5-33.
methotrexate: \*\*Intrathecal Methotrexate administered dependent upon age - ranging from 8 mg to 15 mg.
pegaspargase: 2,500 IU/m2 IM or IV q week (days 6, 12, 19, 26)
prednisone: 40mg/m2/day divided BID (days 5 - 33)
vincristine sulfate: 1.5mg/m2 (max 2 mg) iv push q week (days 5, 12)
|
|---|---|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
7.7%
1/13
|
|
Respiratory, thoracic and mediastinal disorders
Decreased respiratory rate
|
7.7%
1/13
|
|
Infections and infestations
Infection, blood
|
46.2%
6/13
|
|
Musculoskeletal and connective tissue disorders
Pain, generalized body
|
7.7%
1/13
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
7.7%
1/13
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
15.4%
2/13
|
|
Metabolism and nutrition disorders
Hyponatremia
|
7.7%
1/13
|
|
Gastrointestinal disorders
Pancreatitis
|
15.4%
2/13
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
7.7%
1/13
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia - acute respiratory distress
|
7.7%
1/13
|
|
Investigations
Lipase elevated
|
7.7%
1/13
|
|
Nervous system disorders
Cerebral hemorrhage
|
7.7%
1/13
|
|
Gastrointestinal disorders
Pain, abdominal
|
7.7%
1/13
|
|
Metabolism and nutrition disorders
Hypercholesteremia
|
7.7%
1/13
|
Other adverse events
| Measure |
Decitabine / Vorinostat
n=13 participants at risk
This is a therapeutic trial investigating the combination of decitabine 15 mg/m2 and vorinostat 230 mg/m2 (maximum daily dose not to exceed 400 mg) in relapsed/refractory ALL/LL patients prior to induction chemotherapy.
cytarabine: At baseline when peripheral blood draw and bone marrow aspirate performed.
\*Intrathecal Cytarabine administered dependent upon age - ranging from 30 mg to 70 mg.
decitabine: Days 1-4, 15 mg/m\^2 intravenously (IV) over 1 hour
doxorubicin hydrochloride: Day 5, 60 mg/m\^2 intravenously (IV) over 15 minutes
imatinib mesylate: 340 mg/m2 by mouth every day (rounded to the nearest 100 mg) for age \<18 years and 400 mg orally every day for \>18 years on Days 5-33.
methotrexate: \*\*Intrathecal Methotrexate administered dependent upon age - ranging from 8 mg to 15 mg.
pegaspargase: 2,500 IU/m2 IM or IV q week (days 6, 12, 19, 26)
prednisone: 40mg/m2/day divided BID (days 5 - 33)
vincristine sulfate: 1.5mg/m2 (max 2 mg) iv push q week (days 5, 12)
|
|---|---|
|
Blood and lymphatic system disorders
Hemorrhage, bladder
|
7.7%
1/13
|
|
Blood and lymphatic system disorders
Leukocytes decreased
|
23.1%
3/13
|
|
Blood and lymphatic system disorders
Anemia
|
46.2%
6/13
|
|
Blood and lymphatic system disorders
Platelets count decreased
|
23.1%
3/13
|
|
Blood and lymphatic system disorders
Neutrophil count decreased
|
7.7%
1/13
|
|
Blood and lymphatic system disorders
Lymphopenia
|
7.7%
1/13
|
|
Blood and lymphatic system disorders
Platelets
|
15.4%
2/13
|
|
Blood and lymphatic system disorders
Bone marrow cellularity
|
7.7%
1/13
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
46.2%
6/13
|
|
Blood and lymphatic system disorders
Leukocytes
|
15.4%
2/13
|
|
Blood and lymphatic system disorders
Neutrophils
|
7.7%
1/13
|
|
Cardiac disorders
Tachycardia
|
15.4%
2/13
|
|
Cardiac disorders
Hypertension
|
15.4%
2/13
|
|
Cardiac disorders
Ventricular arrythmia
|
7.7%
1/13
|
|
Cardiac disorders
Systolic murmur
|
7.7%
1/13
|
|
Cardiac disorders
Sinus tachycardia
|
7.7%
1/13
|
|
Cardiac disorders
Hypotension
|
7.7%
1/13
|
|
Endocrine disorders
Adrenal insufficiency
|
7.7%
1/13
|
|
Eye disorders
Photophobia
|
7.7%
1/13
|
|
Eye disorders
Blurred vision
|
7.7%
1/13
|
|
Gastrointestinal disorders
Nausea
|
30.8%
4/13
|
|
Gastrointestinal disorders
Constipation
|
38.5%
5/13
|
|
Gastrointestinal disorders
Diarrhea
|
23.1%
3/13
|
|
Gastrointestinal disorders
Vomiting
|
7.7%
1/13
|
|
Gastrointestinal disorders
Pancreatitis
|
7.7%
1/13
|
|
Gastrointestinal disorders
Fluid retention, ascites
|
7.7%
1/13
|
|
Gastrointestinal disorders
Lower molar pain
|
7.7%
1/13
|
|
Gastrointestinal disorders
Abdominal pain
|
46.2%
6/13
|
|
Gastrointestinal disorders
Mucositis
|
30.8%
4/13
|
|
General disorders
Fatigue
|
30.8%
4/13
|
|
General disorders
Edema, lower extremity
|
15.4%
2/13
|
|
General disorders
Edema, upper extremity
|
7.7%
1/13
|
|
General disorders
Generalised body aches
|
7.7%
1/13
|
|
General disorders
Weakness
|
7.7%
1/13
|
|
General disorders
Fever
|
15.4%
2/13
|
|
Infections and infestations
Infection, meningitis
|
7.7%
1/13
|
|
Infections and infestations
Fungal infection, lung
|
7.7%
1/13
|
|
Infections and infestations
Infection, soft tissue
|
7.7%
1/13
|
|
Infections and infestations
Infection, neutopenia
|
15.4%
2/13
|
|
Infections and infestations
Infection, positive blood culture
|
7.7%
1/13
|
|
Injury, poisoning and procedural complications
Pain uncontrolled
|
7.7%
1/13
|
|
Injury, poisoning and procedural complications
Pain, epigastric
|
7.7%
1/13
|
|
Injury, poisoning and procedural complications
Pain, headache
|
7.7%
1/13
|
|
Injury, poisoning and procedural complications
Pain, pedal bilateral
|
7.7%
1/13
|
|
Injury, poisoning and procedural complications
Pain, leg bilateral
|
15.4%
2/13
|
|
Injury, poisoning and procedural complications
Pain, stomach
|
7.7%
1/13
|
|
Injury, poisoning and procedural complications
Pain, left chest
|
7.7%
1/13
|
|
Injury, poisoning and procedural complications
Pain, low back/leg
|
7.7%
1/13
|
|
Injury, poisoning and procedural complications
Lower lip swelling
|
7.7%
1/13
|
|
Injury, poisoning and procedural complications
Pain, NOS
|
7.7%
1/13
|
|
Investigations
Hyperbilirubinemia
|
30.8%
4/13
|
|
Investigations
Weight gain
|
7.7%
1/13
|
|
Investigations
Creatinine
|
7.7%
1/13
|
|
Investigations
Lipase elevated
|
7.7%
1/13
|
|
Investigations
Alkaline phosphatase increased
|
15.4%
2/13
|
|
Investigations
ALT increased
|
30.8%
4/13
|
|
Investigations
Creatinine increased
|
15.4%
2/13
|
|
Investigations
Fibrinogen increased
|
7.7%
1/13
|
|
Investigations
Amylase
|
7.7%
1/13
|
|
Investigations
Lipase
|
7.7%
1/13
|
|
Blood and lymphatic system disorders
ANC
|
7.7%
1/13
|
|
Investigations
Hypomagnesemia
|
7.7%
1/13
|
|
Investigations
AST increased
|
7.7%
1/13
|
|
Investigations
AST
|
7.7%
1/13
|
|
Metabolism and nutrition disorders
Hypermagnesemia
|
15.4%
2/13
|
|
Metabolism and nutrition disorders
Hyponatremia
|
15.4%
2/13
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
38.5%
5/13
|
|
Metabolism and nutrition disorders
Hyperchloremia
|
7.7%
1/13
|
|
Metabolism and nutrition disorders
Hypertriglyceridemia
|
7.7%
1/13
|
|
Metabolism and nutrition disorders
Albumin
|
15.4%
2/13
|
|
Metabolism and nutrition disorders
Calcium
|
15.4%
2/13
|
|
Metabolism and nutrition disorders
Glucose
|
7.7%
1/13
|
|
Metabolism and nutrition disorders
Hypokalemia
|
38.5%
5/13
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
7.7%
1/13
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
23.1%
3/13
|
|
Metabolism and nutrition disorders
Dehydration
|
7.7%
1/13
|
|
Metabolism and nutrition disorders
Anorexia
|
7.7%
1/13
|
|
Metabolism and nutrition disorders
Uric acid increased
|
7.7%
1/13
|
|
Metabolism and nutrition disorders
Calcium decreased
|
15.4%
2/13
|
|
Metabolism and nutrition disorders
Hyperphosphatemia
|
15.4%
2/13
|
|
Metabolism and nutrition disorders
Calcium increased
|
7.7%
1/13
|
|
Metabolism and nutrition disorders
Obesity
|
7.7%
1/13
|
|
Musculoskeletal and connective tissue disorders
Knee pain
|
7.7%
1/13
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.7%
1/13
|
|
Musculoskeletal and connective tissue disorders
Hip pain
|
7.7%
1/13
|
|
Nervous system disorders
Somnolence
|
15.4%
2/13
|
|
Nervous system disorders
Headaches
|
15.4%
2/13
|
|
Nervous system disorders
Hemiparesis, right side
|
7.7%
1/13
|
|
Nervous system disorders
Neuropathy
|
30.8%
4/13
|
|
Psychiatric disorders
Mood alteration, NOS
|
7.7%
1/13
|
|
Psychiatric disorders
Depression
|
15.4%
2/13
|
|
Psychiatric disorders
Anxiety
|
23.1%
3/13
|
|
Psychiatric disorders
Insomnia
|
7.7%
1/13
|
|
Psychiatric disorders
Confusion
|
7.7%
1/13
|
|
Renal and urinary disorders
Chronic kidney disease
|
7.7%
1/13
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
15.4%
2/13
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnea
|
7.7%
1/13
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
7.7%
1/13
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary infiltrate
|
7.7%
1/13
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
23.1%
3/13
|
|
Skin and subcutaneous tissue disorders
Hand foot reaction
|
7.7%
1/13
|
|
Skin and subcutaneous tissue disorders
Demi Erythema
|
7.7%
1/13
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
15.4%
2/13
|
|
Skin and subcutaneous tissue disorders
Ulceration, decubitus
|
7.7%
1/13
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.7%
1/13
|
Additional Information
Dr. Michael Burke, MD
University of Minnesota, Pediatric Hematology Dept.
Phone: 612.672.7422
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place