Trial Outcomes & Findings for Cephalon Decitabine, Arsenic Trioxide and Ascorbic Acid for Myelodysplastic Syndrome (NCT NCT00621023)

Last Updated: 2013-02-04

Results Overview

Complete response and Partial response are defined using 2000 international working group (IWG) criteria. The Primary criteria for a CR is a repeat bone marrow showing \< 5% myeloblasts with normal maturation of all cell lines, with no evidence for dysplasia . A PR meets all the CR criteria except Blasts decreased by \>50% over pretreatment, or a less advanced myelodysplastic syndrome (MDS) French American British (FAB) classification than pretreatment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

7 participants

Primary outcome timeframe

after 4 cycles of therapy

Results posted on

2013-02-04

Participant Flow

Recruitment period occurred from November 2007 to April 2010 at Duke University Medical Center.

1 patient was consented and found to be ineligible, and did not participate in the study.

Participant milestones

Participant milestones
Measure	All Participants Drug: Decitabine, Arsenic Trioxide and Ascorbic Acid for MDS Decitabine, Arsenic Trioxide and Ascorbic Acid : Subjects receive decitabine 20 mg/m2 IV over one hour for days1-5 of each cycle, and arsenic trioxide 0.25 mg/kg IV for days 1-5 of cycle 1 followed by 0.25 mg/kg twice weekly (Mon-Thursday or Tues-Fri) for all remaining cycles. Patients will have transfusion and supportive care therapy administered per the treating physician's discretion. Patients with a response after 4 cycles of therapy may choose to continue on two more cycles of decitabine with arsenic and ascorbic acid given only during the first week of those two additional cycles.
Overall Study STARTED	6
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Reasons for withdrawal
Measure	All Participants Drug: Decitabine, Arsenic Trioxide and Ascorbic Acid for MDS Decitabine, Arsenic Trioxide and Ascorbic Acid : Subjects receive decitabine 20 mg/m2 IV over one hour for days1-5 of each cycle, and arsenic trioxide 0.25 mg/kg IV for days 1-5 of cycle 1 followed by 0.25 mg/kg twice weekly (Mon-Thursday or Tues-Fri) for all remaining cycles. Patients will have transfusion and supportive care therapy administered per the treating physician's discretion. Patients with a response after 4 cycles of therapy may choose to continue on two more cycles of decitabine with arsenic and ascorbic acid given only during the first week of those two additional cycles.
Overall Study Death	5
Overall Study Follow up discontinued	1

Baseline Characteristics

Cephalon Decitabine, Arsenic Trioxide and Ascorbic Acid for Myelodysplastic Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=6 Participants Drug: Decitabine, Arsenic Trioxide and Ascorbic Acid for MDS Decitabine, Arsenic Trioxide and Ascorbic Acid : Subjects receive decitabine 20 mg/m2 IV over one hour for days1-5 of each cycle, and arsenic trioxide 0.25 mg/kg IV for days 1-5 of cycle 1 followed by 0.25 mg/kg twice weekly (Mon-Thursday or Tues-Fri) for all remaining cycles. Patients will have transfusion and supportive care therapy administered per the treating physician's discretion. Patients with a response after 4 cycles of therapy may choose to continue on two more cycles of decitabine with arsenic and ascorbic acid given only during the first week of those two additional cycles.
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=99 Participants
Age, Categorical >=65 years	6 Participants n=99 Participants
Sex: Female, Male Female	3 Participants n=99 Participants
Sex: Female, Male Male	3 Participants n=99 Participants
Region of Enrollment United States	6 participants n=99 Participants

PRIMARY outcome

Timeframe: after 4 cycles of therapy

Outcome measures

Outcome measures
Measure	All Participants n=6 Participants Drug: Decitabine, Arsenic Trioxide and Ascorbic Acid for MDS Decitabine, Arsenic Trioxide and Ascorbic Acid : Subjects receive decitabine 20 mg/m2 IV over one hour for days1-5 of each cycle, and arsenic trioxide 0.25 mg/kg IV for days 1-5 of cycle 1 followed by 0.25 mg/kg twice weekly (Mon-Thursday or Tues-Fri) for all remaining cycles. Patients will have transfusion and supportive care therapy administered per the treating physician's discretion. Patients with a response after 4 cycles of therapy may choose to continue on two more cycles of decitabine with arsenic and ascorbic acid given only during the first week of those two additional cycles.
Number of Patients With an Overall Response of Complete Response (CR) or Partial Response (PR)	0 participants

SECONDARY outcome

Timeframe: Up to 5 years or until death

Number of months a complete or partial response was maintained.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: During the treatment period and for 30 days after last dose of study drug

Any of the following non-hematologic toxicities that causes a patient's therapy to be suspended or discontinued: Creatinine \> 2x baseline value; serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), Total bilirubin \> 2x the upper limit of normal; Febrile neutropenia; Uncontrolled infection; Hepatotoxicity defined as an increase in serum bilirubin, SGOT, or alkaline phosphatase to \>5 times baseline value); nephrotoxicity (defined as serum creatinine \>3.5 times the ULN); neurological impairment (defined as somnolence, seizures, or impaired mentation); severe peripheral neuropathy, or any non-hematologic grade 4 toxic event.

Outcome measures

Outcome measures
Measure	All Participants n=6 Participants Drug: Decitabine, Arsenic Trioxide and Ascorbic Acid for MDS Decitabine, Arsenic Trioxide and Ascorbic Acid : Subjects receive decitabine 20 mg/m2 IV over one hour for days1-5 of each cycle, and arsenic trioxide 0.25 mg/kg IV for days 1-5 of cycle 1 followed by 0.25 mg/kg twice weekly (Mon-Thursday or Tues-Fri) for all remaining cycles. Patients will have transfusion and supportive care therapy administered per the treating physician's discretion. Patients with a response after 4 cycles of therapy may choose to continue on two more cycles of decitabine with arsenic and ascorbic acid given only during the first week of those two additional cycles.
Number of Patients With an Unacceptable Toxicity	4 participants

Adverse Events

All Participants

Serious events: 4 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	All Participants n=6 participants at risk Drug: Decitabine, Arsenic Trioxide and Ascorbic Acid for MDS Decitabine, Arsenic Trioxide and Ascorbic Acid : Subjects receive decitabine 20 mg/m2 IV over one hour for days1-5 of each cycle, and arsenic trioxide 0.25 mg/kg IV for days 1-5 of cycle 1 followed by 0.25 mg/kg twice weekly (Mon-Thursday or Tues-Fri) for all remaining cycles. Patients will have transfusion and supportive care therapy administered per the treating physician's discretion. Patients with a response after 4 cycles of therapy may choose to continue on two more cycles of decitabine with arsenic and ascorbic acid given only during the first week of those two additional cycles.
Vascular disorders Hematoma	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Infections and infestations Infection with Grade 3 or 4 neutrophils - lung (pneumonia)	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Infections and infestations Infection with Grade 3 or 4 neutrophils - Urinary tract not otherwise specified	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Infections and infestations Infection with unknown ANC - urinary tract not otherwise specified	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Cardiac disorders Pain - Cardiac/heart	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Respiratory, thoracic and mediastinal disorders Pleural effusion (non-malignant)	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Blood and lymphatic system disorders Febrile neutropenia (fever of unknown origin without documented infection)	33.3% 2/6 • Number of events 2 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug

Other adverse events

Other adverse events
Measure	All Participants n=6 participants at risk Drug: Decitabine, Arsenic Trioxide and Ascorbic Acid for MDS Decitabine, Arsenic Trioxide and Ascorbic Acid : Subjects receive decitabine 20 mg/m2 IV over one hour for days1-5 of each cycle, and arsenic trioxide 0.25 mg/kg IV for days 1-5 of cycle 1 followed by 0.25 mg/kg twice weekly (Mon-Thursday or Tues-Fri) for all remaining cycles. Patients will have transfusion and supportive care therapy administered per the treating physician's discretion. Patients with a response after 4 cycles of therapy may choose to continue on two more cycles of decitabine with arsenic and ascorbic acid given only during the first week of those two additional cycles.
Blood and lymphatic system disorders Hemoglobin	33.3% 2/6 • Number of events 5 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Investigations Leukocytes (total WBC)	33.3% 2/6 • Number of events 9 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Investigations Neutrophils / granulocytes (ANC / AGC)	33.3% 2/6 • Number of events 13 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Investigations Platelets	33.3% 2/6 • Number of events 7 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Investigations Prolonged QTc interval	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Vascular disorders Hypotension	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
General disorders Fatigue (asthenia, lethargy, malaise)	33.3% 2/6 • Number of events 7 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Psychiatric disorders Insomnia	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
General disorders Rigors/chills	16.7% 1/6 • Number of events 3 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Skin and subcutaneous tissue disorders Sweating (diaphoresis)	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Investigations Weight gain	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Injury, poisoning and procedural complications Bruising (in absence of Grade 3 or 4 thrombocytopenia)	16.7% 1/6 • Number of events 2 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Skin and subcutaneous tissue disorders Dry skin	16.7% 1/6 • Number of events 2 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Skin and subcutaneous tissue disorders Ulceration	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Metabolism and nutrition disorders Anorexia	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Gastrointestinal disorders Constipation	33.3% 2/6 • Number of events 6 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Metabolism and nutrition disorders Dehydration	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Gastrointestinal disorders Diarrhea	16.7% 1/6 • Number of events 2 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Gastrointestinal disorders Heartburn / dyspepsia	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Gastrointestinal disorders Hemorrhoids	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Gastrointestinal disorders Nausea	33.3% 2/6 • Number of events 6 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Gastrointestinal disorders Vomiting	33.3% 2/6 • Number of events 2 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Vascular disorders Hemorrhage / Bleeding - Other	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Skin and subcutaneous tissue disorders Petechiae / purpura (hemorrhage / bleeding into skin or mucosa)	16.7% 1/6 • Number of events 2 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
General disorders Edema: limb	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
General disorders Edema: trunk/genital	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Metabolism and nutrition disorders Albumin, serum-low (hypoalbuminemia)	33.3% 2/6 • Number of events 5 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Investigations Alkaline phosphatase	16.7% 1/6 • Number of events 5 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Investigations ALT, SGPT (serum glutamic pyruvic transaminase)	16.7% 1/6 • Number of events 5 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Investigations AST, SGOT (serum glutamic oxaloacetic transaminase)	16.7% 1/6 • Number of events 4 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Investigations Bilirubin (hyperbilirubinemia)	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Metabolism and nutrition disorders Calcium, serum-low (hypocalcemia)	33.3% 2/6 • Number of events 5 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Investigations Creatinine	16.7% 1/6 • Number of events 3 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Metabolism and nutrition disorders Magnesium, serum-low (hypomagnesemia)	33.3% 2/6 • Number of events 5 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Metabolism and nutrition disorders Potassium, serum-low (hypokalemia)	33.3% 2/6 • Number of events 10 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Musculoskeletal and connective tissue disorders Muscle weakness, generalized or specific area (not due to neuropathy) - Extremity-lower	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Nervous system disorders Cognitive disturbance	16.7% 1/6 • Number of events 2 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Nervous system disorders Dizziness	33.3% 2/6 • Number of events 4 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Psychiatric disorders Mood Alteration - Anxiety	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Psychiatric disorders Mood Alteration - Depression	33.3% 2/6 • Number of events 2 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Nervous system disorders Neuropathy: motor	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Nervous system disorders Neuropathy: sensory	16.7% 1/6 • Number of events 2 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Musculoskeletal and connective tissue disorders Pain - back	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
General disorders Pain - Chest / thorax NOS	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Renal and urinary disorders Pain - kidney	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
General disorders Pain - other	16.7% 1/6 • Number of events 3 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Skin and subcutaneous tissue disorders Pain - skin	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Gastrointestinal disorders Pain - stomach	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Renal and urinary disorders Pain - urethra	16.7% 1/6 • Number of events 2 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Respiratory, thoracic and mediastinal disorders Cough	33.3% 2/6 • Number of events 3 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Respiratory, thoracic and mediastinal disorders Dyspnea (shortness of breath)	33.3% 2/6 • Number of events 4 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Respiratory, thoracic and mediastinal disorders Voice changes / dysarthria (e.g., hoarseness, loss or alteration in voice, laryngitis)	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Renal and urinary disorders Urinary frequency / urgency	33.3% 2/6 • Number of events 2 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug
Infections and infestations Infection with unknown ANC - urinary tract not otherwise specified	16.7% 1/6 • Number of events 1 • During the treatment period and 30 days after last dose of study drug. Adverse Events are included regardless of attribution to study drug

Additional Information

Dr. Carlos de Castro

Duke University Medical Center

Phone: 919-684-8964

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place