Azacitidine and Arsenic Trioxide in Treating Patients With Myelodysplastic Syndromes

NCT00234000 | Terminated Phase 1 DMC

• 2 other identifiers: CDR0000442931UCLA-0408087
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as azacitidine and arsenic trioxide, 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 I/II trial is studying the side effects and best dose of azacitidine when given together with arsenic trioxide and to see how well they work in treating patients with myelodysplastic syndromes.

Conditions

Leukemia; Myelodysplastic Syndromes

Keywords

refractory anemia with excess blasts in transformation; refractory anemia with excess blasts; refractory anemia with ringed sideroblasts; refractory anemia; chronic myelomonocytic leukemia; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability as assessed by NCI CTCAE v3.0 (Phase I)

  Every 28 days upto 8 months

Secondary Outcomes (2)

• Time to disease progression

  Participants are folowed for an average of 1 year after completion of study treatment

• Overall survival

  Participants are followed every 3-12 months for survival

Study Arms (1)

Arm 1

EXPERIMENTAL

see description in intervention

Drug: arsenic trioxide; Drug: azacitidine

Interventions

arsenic trioxide DRUG

Each 28-day treatment cycle will include dosing for 2 days per week of ATO. Subjects will recieve 1 mg/mL each dosing day.

Also known as: ATO

Arm 1

azacitidine DRUG

Each 28-day treatment cycle will include dosing the first five days of cycle with Azacitidine. Cohorts of three to six patients will each receive 25, 50, and 75 mg/m2/d injected subcutaneously.

Arm 1

Eligibility Criteria

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

You may qualify if:

• Confirmed diagnosis of MDS by standard criteria. Patients within each of the FAB diagnostic groups of RA, RARS, RAEB, RAEBt, and CMML are eligible. For patients with lower-risk MDS only: documented red blood cell dependence, defined as the inability to maintain a hematocrit of \> 25% without transfusion support.
• Adequate marrow iron stores
• In patients with serum erythropoietin less than 200 IU/mL at screening, failure to have responded to a 2 to 3 month trial of recombinant erythropoietin
• Serum creatinine or serum bilirubin \< 1.5 times the upper limit of normal; higher levels are acceptable if ALT levels \< 2 x upper limits of normal
• Women of childbearing potential must have a negative serum pregnancy test prior to azacitidine/treatment.
• Women of childbearing potential should be advised to avoid becoming pregnant and should be advised to not father a child while receiving treatment with azacitidine
• Age \> 18 years

You may not qualify if:

• Treatment with growth factors within the 30 days before first treatment with ATO/Azacitidine, except that patients with serum erythropoietin \< 200 IU/mL who failed to respond to a trial with EPO are not excluded regardless of the time since last EPO
• Treatment with cytotoxic or experimental agents within 30 days before first treatment with ATO/Azacitidine
• Absolute QT interval \> 460 msec in the presence of adequate serum potassium and magnesium values
• Active serious infections that are not controlled by antibiotics
• Pregnant or lactating women
• Inability or unwillingness to comply with the treatment protocol, follow-up, or research tests
• NYHA Class III or IV heart failure
• Poorly controlled hypertension, diabetes mellitus, or other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol

Sponsors & Collaborators

• Jonsson Comprehensive Cancer Center: lead
• CTI BioPharma: collaborator
• Celgene Corporation: collaborator

Study Sites (1)

Jonsson Comprehensive Cancer Center at UCLA

Los Angeles, California, 90095-1781, United States

Location

MeSH Terms

Conditions

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

Interventions

Arsenic Trioxide; Azacitidine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; 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; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Gary J. Schiller, MD

  Jonsson Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 5, 2005
• First Posted: October 6, 2005
• Study Start: February 1, 2007
• Primary Completion: February 1, 2009
• Last Updated: July 31, 2020

Record last verified: 2012-08

Locations

US (1)