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

Primary Purpose

Leukemia, Myelodysplastic Syndromes

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
arsenic trioxide
gemtuzumab ozogamicin
Sponsored by
The Cleveland Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring refractory anemia with excess blasts in transformation, refractory anemia with excess blasts, chronic myelomonocytic leukemia, secondary acute myeloid leukemia, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, de novo myelodysplastic syndromes

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

DISEASE CHARACTERISTICS: Diagnosis of one of the following hematologic malignancies: Myelodysplastic syndromes (MDS) of one of the following French-American-British (FAB) classifications: Refractory anemia with excess blasts (RAEB) (WHO RAEB-1) RAEB in transformation (RAEB-t) (RAEB-2) Chronic myelomonocytic leukemia (CMML) with > 5% myeloblasts (WHO CMML-2) International Prognostic Scoring System (IPSS) score of intermediate-2 or higher in the setting of > 5% myeloblasts Acute myeloid leukemia that has evolved from MDS Must not be a candidate for bone marrow transplantation as first-line therapy or must have declined bone marrow transplantation PATIENT CHARACTERISTICS: Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Life expectancy of at least 4 months Serum potassium ≥ 4.0 milliequivalent (mEq/dL) and serum magnesium ≥ 1.8 mg/dL (supplemental electrolytes allowed) Absolute corrected QT interval (QTc) interval < 460 msec No serious medical condition, laboratory abnormality, or psychiatric illness that, in the view of the treating physician, would place the patient at an unacceptable risk if he or she were to participate in the study or would prevent that person from giving informed consent Not pregnant or nursing Fertile patients must be willing to use adequate contraception (barrier method with spermicidal jelly, intrauterine device (IUD), or oral contraceptives) Negative pregnancy test Creatinine > 2.5 mg/dL serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) > 1.5 times upper limit of normal Bilirubin > 2.0 mg/dL No history of malignancy within the past 3 years other than MDS except basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast Arsenic trioxide is contraindicated in patients who are hypersensitive to arsenic PRIOR CONCURRENT THERAPY: No prior bone marrow transplantation Must not receive another investigational or approved therapy for MDS within 4 weeks of study enrollment, including growth factors (within 1 week of study enrollment) No prior arsenic trioxide or gemtuzumab ozogamicin No other concurrent cytotoxic drugs or investigational agents

Sites / Locations

  • Cleveland Clinic Taussig Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ATO + GO

Arm Description

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

Outcomes

Primary Outcome Measures

Complete and Partial Remission Per the International Working Group (IWG) Criteria for Myelodysplastic Syndromes (MDS) or Acute Myeloid Leukemia (AML)
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.

Secondary Outcome Measures

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

Full Information

First Posted
January 10, 2006
Last Updated
July 6, 2015
Sponsor
The Cleveland Clinic
Collaborators
University of Michigan, National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00274781
Brief Title
Arsenic Trioxide and Gemtuzumab Ozogamicin in Treating Patients With Advanced Myelodysplastic Syndromes
Official Title
A Phase II Trial of Combination Therapy With Arsenic Trioxide (Trisenox) and Gemtuzumab Ozogamicin (Mylotarg) for the Treatment of Adult Patients With Advanced Myelodysplastic Syndrome
Study Type
Interventional

2. Study Status

Record Verification Date
July 2015
Overall Recruitment Status
Completed
Study Start Date
February 2004 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
November 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
The Cleveland Clinic
Collaborators
University of Michigan, National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide and gemtuzumab ozogamicin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving arsenic trioxide together with gemtuzumab ozogamicin works in treating patients with advanced myelodysplastic syndromes.
Detailed Description
OBJECTIVES: Primary Determine the efficacy of arsenic trioxide and gemtuzumab ozogamicin to achieve complete and partial remissions in patients with advanced myelodysplastic syndromes. Secondary Determine the efficacy of this regimen, in terms of 50% decrease in Red Blood Cell (RBC) transfusion requirements and change in hemoglobin concentration from baseline in patients treated with this regimen. Determine the platelet, neutrophil, bone marrow, and cytogenic response in patients treated with this regimen. Determine the response duration in patients treated with this regimen. Determine the quality of life of patients treated with this regimen. Determine the safety and toxicity of this regimen in these patients. OUTLINE: This is a multicenter, open-label study. Patients receive arsenic trioxide IV over 1 hour once daily on days 1-5 in week 1 and then twice weekly in weeks 2-12. They also receive gemtuzumab ozogamicin IV over 2 hours on day 8. Treatment repeats every 12 weeks for up to 2 courses in the absence of disease progression or unacceptable toxicity. Quality of life is assessed at baseline, every 12 weeks during study treatment, and then 4 weeks after the completion of study treatment. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myelodysplastic Syndromes
Keywords
refractory anemia with excess blasts in transformation, refractory anemia with excess blasts, chronic myelomonocytic leukemia, secondary acute myeloid leukemia, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, de novo myelodysplastic syndromes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ATO + GO
Arm Type
Experimental
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
arsenic trioxide
Other Intervention Name(s)
Trisenox
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
gemtuzumab ozogamicin
Other Intervention Name(s)
Mylotarg
Intervention Description
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
Primary Outcome Measure Information:
Title
Complete and Partial Remission Per the International Working Group (IWG) Criteria for Myelodysplastic Syndromes (MDS) or Acute Myeloid Leukemia (AML)
Description
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.
Time Frame
at 12 weeks post treatment
Secondary Outcome Measure Information:
Title
Overall Survival
Description
Patient's Overall Survival from date of enrollment to a minimum of three years for survival.
Time Frame
From date of enrollment to a minimum of three years for survival
Title
Tolerability
Description
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.
Time Frame
12 Weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
DISEASE CHARACTERISTICS: Diagnosis of one of the following hematologic malignancies: Myelodysplastic syndromes (MDS) of one of the following French-American-British (FAB) classifications: Refractory anemia with excess blasts (RAEB) (WHO RAEB-1) RAEB in transformation (RAEB-t) (RAEB-2) Chronic myelomonocytic leukemia (CMML) with > 5% myeloblasts (WHO CMML-2) International Prognostic Scoring System (IPSS) score of intermediate-2 or higher in the setting of > 5% myeloblasts Acute myeloid leukemia that has evolved from MDS Must not be a candidate for bone marrow transplantation as first-line therapy or must have declined bone marrow transplantation PATIENT CHARACTERISTICS: Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Life expectancy of at least 4 months Serum potassium ≥ 4.0 milliequivalent (mEq/dL) and serum magnesium ≥ 1.8 mg/dL (supplemental electrolytes allowed) Absolute corrected QT interval (QTc) interval < 460 msec No serious medical condition, laboratory abnormality, or psychiatric illness that, in the view of the treating physician, would place the patient at an unacceptable risk if he or she were to participate in the study or would prevent that person from giving informed consent Not pregnant or nursing Fertile patients must be willing to use adequate contraception (barrier method with spermicidal jelly, intrauterine device (IUD), or oral contraceptives) Negative pregnancy test Creatinine > 2.5 mg/dL serum glutamate oxaloacetate transaminase (SGOT) or serum glutamate pyruvate transaminase (SGPT) > 1.5 times upper limit of normal Bilirubin > 2.0 mg/dL No history of malignancy within the past 3 years other than MDS except basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast Arsenic trioxide is contraindicated in patients who are hypersensitive to arsenic PRIOR CONCURRENT THERAPY: No prior bone marrow transplantation Must not receive another investigational or approved therapy for MDS within 4 weeks of study enrollment, including growth factors (within 1 week of study enrollment) No prior arsenic trioxide or gemtuzumab ozogamicin No other concurrent cytotoxic drugs or investigational agents
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mikkael A. Sekeres, MD, MS
Organizational Affiliation
The Cleveland Clinic
Official's Role
Study Chair
Facility Information:
Facility Name
Cleveland Clinic Taussig Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States

12. IPD Sharing Statement

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

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