Arsenic Trioxide and Etanercept in Treating Patients With Myelodysplastic Syndromes

Leukemia Clinical Trial

Official title:

Therapy of Advanced Stage Myelodysplastic Syndrome (MDS) With Arsenic Trioxide Given in Combination With Etanercept: A Phase I/II Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00093366
• Other study ID #: 1888.00
• Secondary ID: FHCRC-1888.00CDR
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 6, 2004
• Last updated: November 28, 2011
• Start date: June 2004
• Est. completion date: July 2006

Study information

• Verified date: November 2011
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

RATIONALE: Drugs used in chemotherapy, such as arsenic trioxide, work in different ways to stop cancer cells from dividing so they stop growing or die. Biological therapies such as etanercept may interfere with the growth of the cancer cells. Combining chemotherapy with biological therapy may kill more cancer cells.

PURPOSE: This phase I/II trial is studying the side effects of giving arsenic trioxide together with etanercept and to see how well it works in treating patients with myelodysplastic syndromes.

Description:

OBJECTIVES:

• Determine the frequency of hematologic response in patients with intermediate-2 or high-risk myelodysplastic syndromes (MDS) treated with arsenic trioxide and etanercept.

• Determine the efficacy of this regimen in patients with intermediate-1 or low-risk MDS that was refractory to anti-thymocyte globulin and etanercept on protocol FHCRC-1872.

• Correlate results of ex vivo and in vitro studies of phenotypic, cytogenetic, and functional disease characteristics with in vivo treatment response in patients treated with this regimen.

• Determine parameters that are associated with a high probability of disease response in patients treated with this regimen.

OUTLINE: This is a pilot study.

Patients receive arsenic trioxide IV over 1-4 hours on days 1-5 of week 1 and then twice weekly on weeks 2-12 during course 1 (twice weekly on weeks 1-12 during course 2). Patients also receive etanercept subcutaneously twice weekly during weeks 1, 2, 5, 6, 9, and 10. Treatment repeats every 12 weeks for 2 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed for 3 months.

PROJECTED ACCRUAL: A total of 15-32 patients will be accrued for this study within 8-18 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: July 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

DISEASE CHARACTERISTICS:

• Diagnosis of myelodysplastic syndromes (MDS) meeting 1 of the following criteria:

• Intermediate-2 or high-risk disease

• Intermediate-1 or low-risk disease that was refractory to anti-thymocyte globulin and etanercept on protocol FHCRC-1872

• Not eligible for stem cell transplantation for any of the following reasons:

• Suitable bone marrow donor is not available

• Ineligible for a transplantation protocol

• Not willing to undergo transplantation

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count > 500/mm^3

Hepatic

• Not specified

Renal

• Not specified

Cardiovascular

• No evidence of cardiac arrhythmia

• No evidence of congestive heart failure

• QTc interval = 460 msec

Pulmonary

• No pneumonia

Other

• Potassium > 4.0 mEq/L (supplemental electrolytes allowed)

• Magnesium > 1.8 mg/dL (supplemental electrolytes allowed)

• No history of anaphylactic reaction to arsenic trioxide

• No active severe infection (e.g., septicemia) within the past 2 weeks

• No other severe disease that would preclude study compliance

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• See Disease Characteristics

• No prior hematopoietic stem cell transplantation

• More than 4 weeks since prior hematopoietic growth factors for MDS

• More than 4 weeks since prior immunomodulatory therapy for MDS

• No concurrent hematopoietic growth factors for MDS

• No other concurrent immunomodulatory therapy for MDS

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• More than 4 weeks since prior cytotoxic therapy for MDS

• More than 4 weeks since prior experimental therapy for MDS

• No other concurrent cytotoxic therapy for MDS

• No other concurrent experimental therapy for MDS

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Myelodysplastic Syndromes
• Myelodysplastic-Myeloproliferative Diseases
• Myelodysplastic/Myeloproliferative Diseases
• Myeloproliferative Disorders
• Preleukemia
• Syndrome

Intervention

Biological:
• etanercept

Drug:
• arsenic trioxide

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hematologic response in patients with intermediate-2 or high-risk myelodysplastic syndromes			No
Primary	Efficacy of this regimen in patients with intermediate-1 or low-risk MDS that was refractory to anti-thymocyte globulin and etanercept on protocol FHCRC-1872			No
Primary	Correlate results of ex vivo and in vitro studies on phenotypic, cytogenetic, and functional disease characteristics with in vivo treatment responses			No
Primary	Parameters that are associated with a high probability of response			No