Azacitidine and Arsenic Trioxide in Treating Patients With Myelodysplastic Syndromes

This study has been terminated.
(The study was closed due to poor enrollment)
Sponsor:
Collaborators:
CTI BioPharma
Celgene Corporation
Information provided by (Responsible Party):
Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00234000
First received: October 5, 2005
Last updated: August 2, 2012
Last verified: August 2012
  Purpose

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.


Condition Intervention Phase
Leukemia
Myelodysplastic Syndromes
Drug: arsenic trioxide
Drug: azacitidine
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Multicenter Study of Arsenic Trioxide and Azacitidine in Patients With Myelodysplastic Syndromes

Resource links provided by NLM:


Further study details as provided by Jonsson Comprehensive Cancer Center:

Primary Outcome Measures:
  • Safety and tolerability as assessed by NCI CTCAE v3.0 (Phase I) [ Time Frame: Every 28 days upto 8 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Time to disease progression [ Time Frame: Participants are folowed for an average of 1 year after completion of study treatment ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Participants are followed every 3-12 months for survival ] [ Designated as safety issue: No ]

Enrollment: 1
Study Start Date: February 2007
Primary Completion Date: February 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1
see description in intervention
Drug: arsenic trioxide
Each 28-day treatment cycle will include dosing for 2 days per week of ATO. Subjects will recieve 1 mg/mL each dosing day.
Other Name: ATO
Drug: azacitidine
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.

Detailed Description:

OBJECTIVES:

Primary

  • Determine the maximum tolerated dose of azacitidine when given in combination with arsenic trioxide in patients with myelodysplastic syndromes (MDS). (Phase I)
  • Determine the safety and tolerability of this regimen in these patients. (Phase I)
  • Determine the major hematologic response (erythroid response) rate in patients with transfusion-dependent lower-risk MDS treated with this regimen. (Phase II)
  • Determine complete and partial remission rates in patients with higher-risk MDS treated with this regimen. (Phase II)
  • Determine the toxicity profile of this regimen in these patients. (Phase I)

Secondary

  • Determine time to disease progression in patients treated with this regimen. (Phase I and II)
  • Determine the overall and progression-free survival of patients treated with this regimen. (Phase I and II)

OUTLINE: This is an multicenter, open-label, phase I, dose escalation study of azacitidine followed by a phase II study. Patients enrolled in the phase II portion are stratified according to baseline International Scoring System score (lower-risk myelodysplastic syndromes [MDS] vs higher-risk MDS).

  • Phase I: Patients receive azacitidine subcutaneously once daily on days 1-5 and arsenic trioxide IV over 1-4 hours on days 1, 4, 8, 11, 15, 18, 22, and 25. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients with stable disease may receive up to 8 courses of therapy. Patients with responding disease may continue to receive study therapy until a major response or a complete remission is achieved.

Cohorts of 3-6 patients receive escalating doses of azacitidine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

  • Phase II: Patients receive arsenic trioxide as in phase I and azacitidine as in phase I at one dose level below the MTD determined in phase I.

After the completion of study treatment, patients are followed at 4 weeks and then every 3-12 months for survival.

PROJECTED ACCRUAL: Approximately 3-18 patients will be accrued for the phase I portion of this study. A total of 60 patients (30 per stratum) will be accrued for the phase II portion of this study.

  Eligibility

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

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  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: NCT00234000

Locations
United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
CTI BioPharma
Celgene Corporation
Investigators
Principal Investigator: Gary J. Schiller, MD Jonsson Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Jonsson Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00234000     History of Changes
Other Study ID Numbers: CDR0000442931, P30CA016042, UCLA-0408087
Study First Received: October 5, 2005
Last Updated: August 2, 2012
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Jonsson Comprehensive Cancer Center:
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

Additional relevant MeSH terms:
Leukemia
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Azacitidine
Arsenic trioxide
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 15, 2014