Trial Outcomes & Findings for Arsenic Trioxide and Gemtuzumab Ozogamicin in Treating Patients With Advanced Myelodysplastic Syndromes (NCT NCT00274781)

Last Updated: 2015-07-10

Results Overview

The null hypothesis to be tested was the percentage who will respond to combination arsenic trioxide (ATO) and gemtuzumab ozogamicin (GO) therapy is \<10%. A total of \>/= 9 responses observed in 30 evaluable patients was taken as evidence warranting further study of the regimen, provided the toxicity profile also appears favorable. The IWG Criteria standardizes the clinical responses in MDS and AML based upon hematologic improvement, quality of life and cytogenic improvement. These standardizations allow for the responses to be determined as either complete responses or partial responses.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

30 participants

Primary outcome timeframe

at 12 weeks post treatment

Results posted on

2015-07-10

Participant Flow

Patients were enrolled at Cleveland Clinic and the University of Michigan from February 2004 through June 2006.

Participant milestones

Participant milestones
Measure	ATO (0.25mg/kg) and GO (3mg/m2) ATO dosing was based on the phase 2 European Union regimen at a dose of 0.25 mg/kg administered intravenously on Days 1 through 5 during Week 1 and then twice weekly during Weeks 2 to 12, and GO at a dose of 3mg/m2 on Day 8 for 1 or 2 cycles of 12 weeks each.
Overall Study STARTED	30
Overall Study COMPLETED	30
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Arsenic Trioxide and Gemtuzumab Ozogamicin in Treating Patients With Advanced Myelodysplastic Syndromes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ATO (0.25mg/kg) and GO (3mg/m2) n=30 Participants ATO dosing was based on the phase 2 European Union regimen at a dose of 0.25 mg/kg administered intravenously on Days 1 through 5 during Week 1 and then twice weekly during Weeks 2 to 12, and GO at a dose of 3mg/m2 on Day 8 for 1 or 2 cycles of 12 weeks each.
Age, Continuous	69 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	21 Participants n=5 Participants
Region of Enrollment United States	30 participants n=5 Participants

PRIMARY outcome

Timeframe: at 12 weeks post treatment

Population: Responses According to IWG MDS Criteria (n=30) Responses According to IWG AML Criteria (n=12)

Outcome measures

Outcome measures
Measure	ATO + GO n=30 Participants Arsenic Trioxide 0.25 mg/kg D1-5 Week 1/Twice Weekly W2-12 + Gemtuzumab Ozogamicin 3 mg/m\^2 D8 for 1 or 2 Cycles of 12 Weeks each arsenic trioxide: Arsenic trioxide will be administered at a dose of 0.25 mg/kg/day IV over 1-2 hours for 5 consecutive days during the first week. Subsequently, arsenic trioxide will be given at a dose of 0.25mg/kg/day twice a week for 11 additional weeks (weeks 2-12). gemtuzumab ozogamicin: Gemtuzumab ozogamicin consists of a 2 hr infusion at a dose of 3mg/m2 on day 8 of each 12-week cycle. Gemtuzumab ozogamicin should be administered at a minimum of one hour after the completion of the arsenic trioxide infusion
Complete and Partial Remission Per the International Working Group (IWG) Criteria for Myelodysplastic Syndromes (MDS) or Acute Myeloid Leukemia (AML) Responses according to IWG MDS Criteria	30 percentage of patients
Complete and Partial Remission Per the International Working Group (IWG) Criteria for Myelodysplastic Syndromes (MDS) or Acute Myeloid Leukemia (AML) Responses according to IWG AML Criteria	25 percentage of patients
Complete and Partial Remission Per the International Working Group (IWG) Criteria for Myelodysplastic Syndromes (MDS) or Acute Myeloid Leukemia (AML) Responses according to Both Criteria	10 percentage of patients

SECONDARY outcome

Timeframe: From date of enrollment to a minimum of three years for survival

Patient's Overall Survival from date of enrollment to a minimum of three years for survival.

Outcome measures

Outcome measures
Measure	ATO + GO n=30 Participants Arsenic Trioxide 0.25 mg/kg D1-5 Week 1/Twice Weekly W2-12 + Gemtuzumab Ozogamicin 3 mg/m\^2 D8 for 1 or 2 Cycles of 12 Weeks each arsenic trioxide: Arsenic trioxide will be administered at a dose of 0.25 mg/kg/day IV over 1-2 hours for 5 consecutive days during the first week. Subsequently, arsenic trioxide will be given at a dose of 0.25mg/kg/day twice a week for 11 additional weeks (weeks 2-12). gemtuzumab ozogamicin: Gemtuzumab ozogamicin consists of a 2 hr infusion at a dose of 3mg/m2 on day 8 of each 12-week cycle. Gemtuzumab ozogamicin should be administered at a minimum of one hour after the completion of the arsenic trioxide infusion
Overall Survival Overall Survival	9.7 months Interval 0.75 to 38.0
Overall Survival Responders Overall Survival	28.6 months Interval 3.5 to 38.0
Overall Survival Nonresponders Overall Survival	7.6 months Interval 0.75 to 38.0

SECONDARY outcome

Timeframe: 12 Weeks

Tolerability of Therapy was assessed through use of the National Cancer Institute Common Toxicity Criteria (version 3.0). Treatment tolerability was determined based upon whether or not the physician determined therapy was in the patient's best interest, whether the patient wanted to continue therapy or not, whether patients discontinued treatment due to progressive disease, or whether patients discontinued treatment due to toxicity.

Outcome measures

Outcome measures
Measure	ATO + GO n=30 Participants Arsenic Trioxide 0.25 mg/kg D1-5 Week 1/Twice Weekly W2-12 + Gemtuzumab Ozogamicin 3 mg/m\^2 D8 for 1 or 2 Cycles of 12 Weeks each arsenic trioxide: Arsenic trioxide will be administered at a dose of 0.25 mg/kg/day IV over 1-2 hours for 5 consecutive days during the first week. Subsequently, arsenic trioxide will be given at a dose of 0.25mg/kg/day twice a week for 11 additional weeks (weeks 2-12). gemtuzumab ozogamicin: Gemtuzumab ozogamicin consists of a 2 hr infusion at a dose of 3mg/m2 on day 8 of each 12-week cycle. Gemtuzumab ozogamicin should be administered at a minimum of one hour after the completion of the arsenic trioxide infusion
Tolerability Patients Who Completed 1 12-Week Cycle (C1)	17 participants
Tolerability Patients Who Completed 2 12-Week Cycles (C2)	7 participants
Tolerability Discontinue Tx During C1: Patient/Physician Choice	5 participants
Tolerability Discontinue Tx During C1: Progressive Disease	5 participants
Tolerability Discontinue Tx During C1:Treatment Toxicity	3 participants
Tolerability Discontinue Tx After C1: Progressive Disease	8 participants
Tolerability Discontinue Tx After C1: Treatment Toxicity	2 participants

Adverse Events

ATO (0.25mg/kg) and GO (3mg/m2)

Serious events: 19 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	ATO (0.25mg/kg) and GO (3mg/m2) n=30 participants at risk ATO dosing was based on the phase 2 European Union regimen at a dose of 0.25 mg/kg administered intravenously on Days 1 through 5 during Week 1 and then twice weekly during Weeks 2 to 12, and GO at a dose of 3mg/m2 on Day 8 for 1 or 2 cycles of 12 weeks each.
Vascular disorders Thrombocytopenia	46.7% 14/30 • 12 Weeks of Therapy
Blood and lymphatic system disorders Neutropenia	63.3% 19/30 • 12 Weeks of Therapy
Blood and lymphatic system disorders Anemia	36.7% 11/30 • 12 Weeks of Therapy
Musculoskeletal and connective tissue disorders Fatigue	13.3% 4/30 • 12 Weeks of Therapy
Gastrointestinal disorders Nausea / Vomiting / Dyspepsia	3.3% 1/30 • 12 Weeks of Therapy
Gastrointestinal disorders Diarrhea / Constipation	3.3% 1/30 • 12 Weeks of Therapy
Respiratory, thoracic and mediastinal disorders Dyspnea	13.3% 4/30 • 12 Weeks of Therapy
Infections and infestations Pneumonia	16.7% 5/30 • 12 Weeks of Therapy
Cardiac disorders QT / QTc Interval Prolongation	10.0% 3/30 • 12 Weeks of Therapy

Other adverse events

Other adverse events
Measure	ATO (0.25mg/kg) and GO (3mg/m2) n=30 participants at risk ATO dosing was based on the phase 2 European Union regimen at a dose of 0.25 mg/kg administered intravenously on Days 1 through 5 during Week 1 and then twice weekly during Weeks 2 to 12, and GO at a dose of 3mg/m2 on Day 8 for 1 or 2 cycles of 12 weeks each.
Vascular disorders Thrombocytopenia	53.3% 16/30 • 12 Weeks of Therapy
Blood and lymphatic system disorders Neutropenia	66.7% 20/30 • 12 Weeks of Therapy
Blood and lymphatic system disorders Anemia	73.3% 22/30 • 12 Weeks of Therapy
Musculoskeletal and connective tissue disorders Fatigue	93.3% 28/30 • 12 Weeks of Therapy
Skin and subcutaneous tissue disorders Rash / Pruritis	40.0% 12/30 • 12 Weeks of Therapy
Musculoskeletal and connective tissue disorders Pain	53.3% 16/30 • 12 Weeks of Therapy
Blood and lymphatic system disorders Edema	30.0% 9/30 • 12 Weeks of Therapy
Gastrointestinal disorders Nausea / Vomiting / Dyspepsia	60.0% 18/30 • 12 Weeks of Therapy
Gastrointestinal disorders Diarrhea / Constipation	66.7% 20/30 • 12 Weeks of Therapy
Respiratory, thoracic and mediastinal disorders Dyspnea	50.0% 15/30 • 12 Weeks of Therapy
Metabolism and nutrition disorders Anorexia / Decreased Appetite	33.3% 10/30 • 12 Weeks of Therapy
Immune system disorders Pyrexia	50.0% 15/30 • 12 Weeks of Therapy
Respiratory, thoracic and mediastinal disorders Cough	36.7% 11/30 • 12 Weeks of Therapy
General disorders Insomnia	13.3% 4/30 • 12 Weeks of Therapy
Infections and infestations Catheter / Infusion Site Disorders / Infections	13.3% 4/30 • 12 Weeks of Therapy
Musculoskeletal and connective tissue disorders Abdominal Pain	20.0% 6/30 • 12 Weeks of Therapy
Cardiac disorders Cardiac Arrhythmia	26.7% 8/30 • 12 Weeks of Therapy
Infections and infestations Pneumonia	26.7% 8/30 • 12 Weeks of Therapy
Nervous system disorders Headache	36.7% 11/30 • 12 Weeks of Therapy
Cardiac disorders QT / QTc Interval Prolongation	13.3% 4/30 • 12 Weeks of Therapy
Immune system disorders Chills / Rigors	53.3% 16/30 • 12 Weeks of Therapy
Nervous system disorders Dizziness / Vertigo	20.0% 6/30 • 12 Weeks of Therapy
Blood and lymphatic system disorders Ecchymosis / Petechiae	16.7% 5/30 • 12 Weeks of Therapy
Nervous system disorders Neuropathy	6.7% 2/30 • 12 Weeks of Therapy

Additional Information

Mikkael Sekeres, MD, MS

The Cleveland Clinic

Phone: 216-445-9353

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place