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

NCT00274781 | Completed Phase 2 Results

• 3 other identifiers: CCF6818P30CA043703CCF-6818
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• 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.

  at 12 weeks post treatment

Secondary Outcomes (2)

• Overall Survival

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

• Tolerability

  12 Weeks

Study Arms (1)

ATO + GO

EXPERIMENTAL

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

Drug: arsenic trioxide; Drug: gemtuzumab ozogamicin

Interventions

arsenic trioxide DRUG

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).

Also known as: Trisenox

ATO + GO

gemtuzumab ozogamicin DRUG

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

Also known as: Mylotarg

ATO + GO

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• The Cleveland Clinic: lead
• University of Michigan: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Cleveland Clinic Taussig Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Anemia, Refractory, with Excess of Blasts; Leukemia, Myelomonocytic, Chronic

Interventions

Arsenic Trioxide; Gemtuzumab

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Anemia, Refractory; Anemia; Leukemia, Myeloid; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Arsenicals; Inorganic Chemicals; Oxides; Oxygen Compounds; Calicheamicins; Aminoglycosides; Glycosides; Carbohydrates; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Mikkael Sekeres, MD, MS
• Organization: The Cleveland Clinic

sekerem@ccf.org

216-445-9353

Study Officials

• Mikkael A. Sekeres, MD, MS

  The Cleveland Clinic

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2006
• First Posted: January 11, 2006
• Study Start: February 1, 2004
• Primary Completion: December 1, 2008
• Study Completion: November 1, 2010
• Last Updated: July 10, 2015
• Results First Posted: July 10, 2015

Record last verified: 2015-07

Locations

US (1)