Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

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

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
The Cleveland Clinic
ClinicalTrials.gov Identifier:
NCT00274781
First received: January 10, 2006
Last updated: May 24, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention Phase
Leukemia
Myelodysplastic Syndromes
Drug: arsenic trioxide
Drug: gemtuzumab ozogamicin
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by The Cleveland Clinic:

Primary Outcome Measures:
  • Complete and partial remission [ Time Frame: at 12 weeks post treatment ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: June 2004
Study Completion Date: December 2010
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: 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).
    Other Name: Trisenox
    Drug: 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 aresenic trioxide infustion
    Other Name: Mylotarg
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 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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of one of the following hematologic malignancies:

    • Myelodysplastic syndromes (MDS) of one of the following 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)
    • 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:

  • ECOG performance status of 0, 1, or 2
  • Life expectancy of at least 4 months
  • Serum potassium ≥ 4.0 mEq/dL and serum magnesium ≥ 1.8 mg/dL (supplemental electrolytes allowed)
  • Absolute 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, IUD, or oral contraceptives)
  • Negative pregnancy test
  • Creatinine > 2.5 mg/dL
  • SGOT or 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00274781

Locations
United States, Ohio
Cleveland Clinic Taussig Cancer Center
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
The Cleveland Clinic
Investigators
Study Chair: Mikkael A. Sekeres, MD, MS The Cleveland Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT00274781     History of Changes
Other Study ID Numbers: CCF6818, P30CA043703, CCF-6818
Study First Received: January 10, 2006
Last Updated: May 24, 2012
Health Authority: United States: Federal Government

Keywords provided by The Cleveland Clinic:
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

Additional relevant MeSH terms:
Leukemia
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Arsenic trioxide
Gemtuzumab
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014