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Trial record 46 of 188 for:    "Acute megakaryoblastic leukemia"

Vorinostat, Azacitidine, and Gemtuzumab Ozogamicin for Older Patients With Relapsed or Refractory AML

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ClinicalTrials.gov Identifier: NCT00895934
Recruitment Status : Completed
First Posted : May 8, 2009
Results First Posted : February 6, 2015
Last Update Posted : February 6, 2015
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Adult Acute Megakaryoblastic Leukemia (M7)
Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
Adult Acute Monoblastic Leukemia (M5a)
Adult Acute Monocytic Leukemia (M5b)
Adult Acute Myeloblastic Leukemia With Maturation (M2)
Adult Acute Myeloblastic Leukemia Without Maturation (M1)
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Adult Acute Myelomonocytic Leukemia (M4)
Adult Erythroleukemia (M6a)
Adult Pure Erythroid Leukemia (M6b)
Recurrent Adult Acute Myeloid Leukemia
Interventions Drug: vorinostat
Drug: gemtuzumab ozogamicin
Drug: azacitidine
Enrollment 53
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Phase 1 Dose-Finding Cohorts 1-3 Phase 2/Selected Dose
Hide Arm/Group Description

Patients receive vorinostat orally on days 1-9, azacitidine subcutaneously (SC) or IV over 10-40 minutes on days 1-7, and gemtuzumab ozogamicin IV over 2 hours on day 8. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

vorinostat: Given orally

gemtuzumab ozogamicin: Given IV

azacitidine: Given IV or SC

laboratory biomarker analysis: Correlative studies

Azacitidine 75 mg/m2 on days 1-7, vorinostat 400 mg qd on days 1-9, gemtuzumab ozogamicin 3 mg/m2 on days 4 and 8. Includes cohort 4 from the Phase 1 portion of the study.
Period Title: Overall Study
Started 10 43
Completed 4 18
Not Completed 6 25
Reason Not Completed
Lack of Efficacy             5             24
Death             0             1
ineligible             1             0
Arm/Group Title Phase 1 Dose-Finding Cohorts 1-3 Phase 2/Selected Dose Total
Hide Arm/Group Description

Patients receive vorinostat PO on days 1-9, azacitidine SC or IV over 10-40 minutes on days 1-7, and gemtuzumab ozogamicin IV over 2 hours on day 8. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

vorinostat: Given orally

gemtuzumab ozogamicin: Given IV

azacitidine: Given IV or SC

laboratory biomarker analysis: Correlative studies

Azacitidine 75 mg/m2 SC or IV on days 1-7, vorinostat 400 mg qd po on days 1-9, gemtuzumab ozogamicin 3 mg/m2 IV on days 4 and 8. Includes cohort 4 from the Phase 1 portion of the study. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Total of all reporting groups
Overall Number of Baseline Participants 10 43 53
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 43 participants 53 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
5
  50.0%
21
  48.8%
26
  49.1%
>=65 years
5
  50.0%
22
  51.2%
27
  50.9%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 43 participants 53 participants
Female
5
  50.0%
18
  41.9%
23
  43.4%
Male
5
  50.0%
25
  58.1%
30
  56.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 43 participants 53 participants
American Indian or Alaska Native
1
  10.0%
0
   0.0%
1
   1.9%
Asian
0
   0.0%
6
  14.0%
6
  11.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
1
   2.3%
1
   1.9%
White
9
  90.0%
34
  79.1%
43
  81.1%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
2
   4.7%
2
   3.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 10 participants 43 participants 53 participants
Hispanic or Latino
3
  30.0%
1
   2.3%
4
   7.5%
Not Hispanic or Latino
7
  70.0%
40
  93.0%
47
  88.7%
Unknown or Not Reported
0
   0.0%
2
   4.7%
2
   3.8%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 10 participants 43 participants 53 participants
10 43 53
1.Primary Outcome
Title Dose-limiting Toxicity and Maximum Tolerated Dose of Vorinostat (Phase I)
Hide Description [Not Specified]
Time Frame 42 days
Outcome Measure Data Not Reported
2.Primary Outcome
Title Efficacy Defined as Best Response Achieved During Study Treatment Measured by Complete Remission (CR) Rate
Hide Description [Not Specified]
Time Frame Up to 3 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Phase 1 Dose-Finding Cohorts 1-3 Phase 2/Selected Dose
Hide Arm/Group Description:

Patients receive vorinostat PO on days 1-9, azacitidine SC or IV over 10-40 minutes on days 1-7, and gemtuzumab ozogamicin IV over 2 hours on day 8. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

vorinostat: Given orally

gemtuzumab ozogamicin: Given IV

azacitidine: Given IV or SC

laboratory biomarker analysis: Correlative studies

Azacitidine 75 mg/m2 on days 1-7, vorinostat 400 mg qd on days 1-9, gemtuzumab ozogamicin 3 mg/m2 on days 4 and 8. Includes cohort 4 from the Phase 1 portion of the study.
Overall Number of Participants Analyzed 9 43
Measure Type: Number
Unit of Measure: participants
4 18
3.Secondary Outcome
Title Relapse-free Survival (RFS)
Hide Description Estimated using Kaplan-Meier method. Logistic regression will be used as a tool to assess the association of various factors with the probability of response, recognizing that the power to detect statistically significant associations will be limited due to the sample size (and expected number of responses). The impact of remission and post-remission therapy on RFS will be assessed using Cox regression with remission and therapy treated as time-dependent covariates.
Time Frame Up to 3 years
Outcome Measure Data Not Reported
Time Frame Adverse events are collected from the start of treatment until 30 days after the last dose.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Phase 1 Dose-Finding Cohorts 1-3 Phase 2/Selected Dose
Hide Arm/Group Description

Patients receive vorinostat PO on days 1-9, azacitidine SC or IV over 10-40 minutes on days 1-7, and gemtuzumab ozogamicin IV over 2 hours on day 8. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Laboratory biomarker analysis: correlative studies

Azacitidine 75 mg/m2 on days 1-7, vorinostat 400 mg qd on days 1-9, gemtuzumab ozogamicin 3 mg/m2 on days 4 and 8. Includes cohort 4 from the Phase 1 portion of the study.

Laboratory biomarker analysis: correlative studies

All-Cause Mortality
Phase 1 Dose-Finding Cohorts 1-3 Phase 2/Selected Dose
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Phase 1 Dose-Finding Cohorts 1-3 Phase 2/Selected Dose
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/10 (60.00%)      13/43 (30.23%)    
Blood and lymphatic system disorders     
febrile neutropenia  1  2/10 (20.00%)  3 1/43 (2.33%)  1
Cardiac disorders     
hypotension  1  1/10 (10.00%)  1 2/43 (4.65%)  2
General disorders     
multi-organ failure  1  0/10 (0.00%)  0 1/43 (2.33%)  1
death, NOS  1  1/10 (10.00%)  1 1/43 (2.33%)  1
Infections and infestations     
infection with neutropenia  1  1/10 (10.00%)  2 1/43 (2.33%)  2
sepsis  1  0/10 (0.00%)  0 4/43 (9.30%)  4
Metabolism and nutrition disorders     
hypokalemia  1  0/10 (0.00%)  0 2/43 (4.65%)  3
Respiratory, thoracic and mediastinal disorders     
hypoxia  1  1/10 (10.00%)  1 1/43 (2.33%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Phase 1 Dose-Finding Cohorts 1-3 Phase 2/Selected Dose
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   9/10 (90.00%)      43/43 (100.00%)    
Blood and lymphatic system disorders     
bleeding  1  4/10 (40.00%)  4 19/43 (44.19%)  19
anemia  1  8/10 (80.00%)  11 25/43 (58.14%)  33
pancytopenia  1  0/10 (0.00%)  0 13/43 (30.23%)  17
febrile neutropenia  1  1/10 (10.00%)  1 31/43 (72.09%)  44
lymphopenia  1  4/10 (40.00%)  6 0/43 (0.00%)  0
neutropenia  1  3/10 (30.00%)  4 17/43 (39.53%)  26
thrombocytopenia  1  5/10 (50.00%)  6 25/43 (58.14%)  38
leukopenia  1  6/10 (60.00%)  7 23/43 (53.49%)  32
Cardiac disorders     
cardiac chest pain  1  0/10 (0.00%)  0 2/43 (4.65%)  2
prolonged QTc  1  0/10 (0.00%)  0 4/43 (9.30%)  4
hypertension  1  1/10 (10.00%)  1 9/43 (20.93%)  11
hypotension  1  2/10 (20.00%)  2 9/43 (20.93%)  9
sinus tachycardia  1  1/10 (10.00%)  1 14/43 (32.56%)  17
Gastrointestinal disorders     
colitis  1  0/10 (0.00%)  0 4/43 (9.30%)  4
constipation  1  5/10 (50.00%)  6 15/43 (34.88%)  18
diarrhea  1  5/10 (50.00%)  5 22/43 (51.16%)  26
mucositis  1  0/10 (0.00%)  0 6/43 (13.95%)  7
nausea  1  8/10 (80.00%)  10 33/43 (76.74%)  47
vomiting  1  6/10 (60.00%)  8 17/43 (39.53%)  25
General disorders     
abdominal pain  1  1/10 (10.00%)  1 5/43 (11.63%)  6
chills  1  2/10 (20.00%)  2 19/43 (44.19%)  19
edema  1  2/10 (20.00%)  2 11/43 (25.58%)  12
fatigue  1  4/10 (40.00%)  5 29/43 (67.44%)  39
fever  1  0/10 (0.00%)  0 16/43 (37.21%)  20
pain  1  3/10 (30.00%)  4 14/43 (32.56%)  15
malaise  1  0/10 (0.00%)  0 3/43 (6.98%)  3
Hepatobiliary disorders     
elevated liver function tests  1  6/10 (60.00%)  14 15/43 (34.88%)  32
Immune system disorders     
allergic reaction  1  0/10 (0.00%)  0 2/43 (4.65%)  3
infusion reaction  1  0/10 (0.00%)  0 4/43 (9.30%)  5
Infections and infestations     
infection  1  5/10 (50.00%)  9 37/43 (86.05%)  43
sepsis  1  0/10 (0.00%)  0 9/43 (20.93%)  9
Injury, poisoning and procedural complications     
fall  1  0/10 (0.00%)  0 3/43 (6.98%)  4
Metabolism and nutrition disorders     
acidosis  1  1/10 (10.00%)  1 2/43 (4.65%)  2
blood chemistry changes  1  9/10 (90.00%)  67 43/43 (100.00%)  86
anorexia  1  1/10 (10.00%)  1 23/43 (53.49%)  34
Musculoskeletal and connective tissue disorders     
back pain  1  0/10 (0.00%)  0 3/43 (6.98%)  3
bone pain  1  0/10 (0.00%)  0 2/43 (4.65%)  2
muscle weakness  1  0/10 (0.00%)  0 5/43 (11.63%)  6
non-cardiac chest pain  1  2/10 (20.00%)  3 3/43 (6.98%)  3
Nervous system disorders     
dizziness  1  2/10 (20.00%)  3 11/43 (25.58%)  11
headache  1  2/10 (20.00%)  2 8/43 (18.60%)  9
Psychiatric disorders     
anxiety  1  0/10 (0.00%)  0 7/43 (16.28%)  7
confusion  1  0/10 (0.00%)  0 8/43 (18.60%)  8
depression  1  2/10 (20.00%)  3 4/43 (9.30%)  4
Renal and urinary disorders     
acute kidney injury  1  1/10 (10.00%)  1 5/43 (11.63%)  5
Respiratory, thoracic and mediastinal disorders     
aspiration  1  0/10 (0.00%)  0 4/43 (9.30%)  4
cough  1  0/10 (0.00%)  0 16/43 (37.21%)  17
dyspnea  1  1/10 (10.00%)  1 14/43 (32.56%)  14
hypoxia  1  0/10 (0.00%)  0 8/43 (18.60%)  9
pleural effusion  1  0/10 (0.00%)  0 5/43 (11.63%)  5
pulmonary edema  1  0/10 (0.00%)  0 4/43 (9.30%)  4
respiratory failure  1  0/10 (0.00%)  0 3/43 (6.98%)  3
wheezing  1  0/10 (0.00%)  0 3/43 (6.98%)  3
Skin and subcutaneous tissue disorders     
erythema multiforme  1  0/10 (0.00%)  0 3/43 (6.98%)  3
skin disorders  1  3/10 (30.00%)  3 15/43 (34.88%)  15
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (3.0)
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
Name/Title: Roland B. Walter, MD, PhD
Organization: Fred Hutchinson Cancer Research Center
Phone: 206-667-3599
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00895934     History of Changes
Other Study ID Numbers: NCI-2012-01147
NCI-2012-01147 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
IR-6921 ( Other Identifier: Fred Hutchinson Cancer Research Center )
CDR0000642213 ( Other Identifier: FDA Center for Drug Research )
2288.00 ( Other Identifier: Fred Hutchinson Cancer Research Center )
8297 ( Other Identifier: CTEP )
P30CA015704 ( U.S. NIH Grant/Contract )
First Submitted: May 7, 2009
First Posted: May 8, 2009
Results First Submitted: August 6, 2014
Results First Posted: February 6, 2015
Last Update Posted: February 6, 2015