Clinical trial NCT00274781: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: 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
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
Collaborators: name: University of Michigan
name: National Cancer Institute (NCI)
First posted: 2006-01-11
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Complete and Partial Remission Per the International Working Group (IWG) Criteria for Myelodysplastic Syndromes (MDS) or Acute Myeloid Leukemia (AML)
timeFrame: at 12 weeks post treatment
Secondary outcomes:
measure: Overall Survival
timeFrame: From date of enrollment to a minimum of three years for survival
measure: Tolerability
timeFrame: 12 Weeks
Other outcomes:
Locations:
city: Cleveland
country: United States
facility: Cleveland Clinic Taussig Cancer Center
state: Ohio
Study officials:
affiliation: The Cleveland Clinic
name: Mikkael A. Sekeres, MD, MS
role: STUDY_CHAIR
References: