Trial Outcomes & Findings for Phase II 5-Azacytidine Plus VPA Plus ATRA (NCT NCT00326170)

NCT ID: NCT00326170

Last Updated: 2012-06-15

Results Overview

Clinical activity of combination defined as: Complete Response (CR), bone marrow with 5% or fewer blasts and peripheral blood count with an absolute neutrophil count of 10\^9/L or more and platelet count of 100x10\^9 or more; Complete response without platelets (CRp), a complete response except for a platelet count less than 100x10\^9 and transfusion independent; and Bone Marrow (BM) Response, bone marrow blast of 5% or less but without meeting the peripheral blood count criteria for (CR) or (CRp).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

34 participants

Primary outcome timeframe

Up to 12 cycles of treatment (28 day cycles)

Results posted on

2012-06-15

Participant Flow

Recruitment Period: 06/10/05 through 11/17/06. All participants recruited at UT MD Anderson Cancer Center.

Participant milestones

Participant milestones
Measure
VPA + 5-aza + ATRA
Daily for 7 days, Valproic acid (VPA) starting dose 75 mg/m\^2 subcutaneously in combination with 5-azacytidine (5-aza) 50 mg/kg orally; and all-trans retinoic acid (ATRA) 45 mg/m\^2 orally daily (in two divided doses) for 5 days starting on day 3.
Overall Study
STARTED
34
Overall Study
COMPLETED
34
Overall Study
NOT COMPLETED
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Phase II 5-Azacytidine Plus VPA Plus ATRA

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
VPA + 5-aza + ATRA
n=34 Participants
Daily for 7 days, Valproic acid (VPA) starting dose 75 mg/m\^2 subcutaneously in combination with 5-azacytidine (5-aza) 50 mg/kg orally; and all-trans retinoic acid (ATRA) 45 mg/m\^2 orally daily (in two divided doses) for 5 days starting on day 3.
Age Continuous
70 years
n=5 Participants
Sex: Female, Male
Female
11 Participants
n=5 Participants
Sex: Female, Male
Male
23 Participants
n=5 Participants
Region of Enrollment
United States
34 participants
n=5 Participants

PRIMARY outcome

Timeframe: Up to 12 cycles of treatment (28 day cycles)

Clinical activity of combination defined as: Complete Response (CR), bone marrow with 5% or fewer blasts and peripheral blood count with an absolute neutrophil count of 10\^9/L or more and platelet count of 100x10\^9 or more; Complete response without platelets (CRp), a complete response except for a platelet count less than 100x10\^9 and transfusion independent; and Bone Marrow (BM) Response, bone marrow blast of 5% or less but without meeting the peripheral blood count criteria for (CR) or (CRp).

Outcome measures

Outcome measures
Measure
VPA + 5-aza + ATRA
n=34 Participants
Daily for 7 days, Valproic acid (VPA) starting dose 75 mg/m\^2 subcutaneously in combination with 5-azacytidine (5-aza) 50 mg/kg orally; and all-trans retinoic acid (ATRA) 45 mg/m\^2 orally daily (in two divided doses) for 5 days starting on day 3.
Number of Participants With Response
CR
12 Participants
Number of Participants With Response
CRp
3 Participants
Number of Participants With Response
BM
7 Participants

Adverse Events

VPA + 5-aza + ATRA

Serious events: 31 serious events
Other events: 11 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
VPA + 5-aza + ATRA
n=34 participants at risk
Daily for 7 days, Valproic acid (VPA) starting dose 75 mg/m\^2 subcutaneously in combination with 5-azacytidine (5-aza) 50 mg/kg orally; and all-trans retinoic acid (ATRA) 45 mg/m\^2 orally daily (in two divided doses) for 5 days starting on day 3.
Infections and infestations
Infection
23.5%
8/34 • Number of events 8 • 2 Years
General disorders
Death
32.4%
11/34 • Number of events 11 • 2 Years
General disorders
Fatigue
20.6%
7/34 • Number of events 8 • 2 Years
Gastrointestinal disorders
Diarrhea
11.8%
4/34 • Number of events 4 • 2 Years
Nervous system disorders
Somnolence
29.4%
10/34 • Number of events 11 • 2 Years
Nervous system disorders
Syncope
5.9%
2/34 • Number of events 2 • 2 Years
Nervous system disorders
Confusion
11.8%
4/34 • Number of events 4 • 2 Years
General disorders
Pain
11.8%
4/34 • Number of events 4 • 2 Years
Blood and lymphatic system disorders
Thrombocytopenia
11.8%
4/34 • Number of events 4 • 2 Years
Metabolism and nutrition disorders
Hyperglycemia
2.9%
1/34 • Number of events 1 • 2 Years
Skin and subcutaneous tissue disorders
Rash
5.9%
2/34 • Number of events 2 • 2 Years
Gastrointestinal disorders
Dehydration
5.9%
2/34 • Number of events 2 • 2 Years
Gastrointestinal disorders
Constipation
2.9%
1/34 • Number of events 1 • 2 Years
Blood and lymphatic system disorders
Pancytopenia
5.9%
2/34 • Number of events 2 • 2 Years
Cardiac disorders
Atrial Fibrillation
2.9%
1/34 • Number of events 1 • 2 Years
Vascular disorders
Hemorrhage
5.9%
2/34 • Number of events 2 • 2 Years
General disorders
Fever
2.9%
1/34 • Number of events 1 • 2 Years
Blood and lymphatic system disorders
Edema
2.9%
1/34 • Number of events 2 • 2 Years

Other adverse events

Other adverse events
Measure
VPA + 5-aza + ATRA
n=34 participants at risk
Daily for 7 days, Valproic acid (VPA) starting dose 75 mg/m\^2 subcutaneously in combination with 5-azacytidine (5-aza) 50 mg/kg orally; and all-trans retinoic acid (ATRA) 45 mg/m\^2 orally daily (in two divided doses) for 5 days starting on day 3.
General disorders
Weakness
14.7%
5/34 • Number of events 5 • 2 Years
Gastrointestinal disorders
Vomiting
2.9%
1/34 • Number of events 1 • 2 Years
General disorders
Fatigue
2.9%
1/34 • Number of events 1 • 2 Years
Nervous system disorders
Confusion
11.8%
4/34 • Number of events 4 • 2 Years
Respiratory, thoracic and mediastinal disorders
Cough
2.9%
1/34 • Number of events 1 • 2 Years
Nervous system disorders
Somnolence
5.9%
2/34 • Number of events 2 • 2 Years
General disorders
Fever
2.9%
1/34 • Number of events 1 • 2 Years
Renal and urinary disorders
Nocturia
2.9%
1/34 • Number of events 1 • 2 Years

Additional Information

Guillermo Garcia-Manero, MD / Associate Professor

UT MD Anderson Cancer Center

Phone: 713-792-7305

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place