Azacitidine and Etanercept in Treating Patients With Myelodysplastic Syndromes

Condition(s) targeted: Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases

Intervention: azacitidine (Drug); etanercept (Drug)

Phase: Phase 1/Phase 2

Status: Active, not recruiting

Sponsored by: Fred Hutchinson Cancer Research Center

Official(s) and/or principal investigator(s):
Bart L. Scott, MD, Principal Investigator, Affiliation: Fred Hutchinson Cancer Research Center

RATIONALE: Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Biological therapies, such as etanercept, may interfere with the growth of cancer cells. Giving azacitidine together with etanercept may kill more cancer cells.

PURPOSE: This phase I/II trial is studying how well giving azacitidine together with etanercept works in treating patients with myelodysplastic syndromes.

Official title: Therapy of Myelodysplastic Syndrome (MDS) With Azacitidine Given in Combination With Etanercept: A Phase I/II Study

Study design: Treatment, Open Label

Primary outcome:

Hematologic response in patients with intermediate-2- or high-risk myelodysplastic syndromes (MDS) treated with azacitidine and etanercept

Efficacy of this regimen in patients with intermediate-1- or low-risk MDS that failed prior anti-thymocyte globulin and etanercept on protocol FHCRC-1872.00

Correlate results of ex vivo and in vitro studies on phenotypic, cytogenetic, and functional disease characteristics with in vivo treatment responses

Parameters that are associated with a high probability of response

Detailed description: OBJECTIVES:

- Determine the frequency of hematologic response in patients with intermediate-2- or

high-risk myelodysplastic syndromes (MDS) treated with azacitidine and etanercept.

- Determine the efficacy of this regimen in patients with intermediate-1- or low-risk MDS

that failed prior anti-thymocyte globulin and etanercept on protocol FHCRC-1872. 00.

- Correlate ex vivo and in vitro phenotypic, cytogenetic, and functional disease

characteristics with in vivo response in patients treated with this regimen.

- Determine parameters associated with a high probability of response in patients treated

with this regimen.

OUTLINE: This is a multicenter study.

Patients receive azacitidine subcutaneously (SC) on days 1-7. Patients also receive etanercept SC on days 8, 11, 15, and 18. Treatment repeats every 28 days for at least 3 courses. Patients with a complete or partial response, evidence of hematologic improvement, or stable disease after 3 courses continue to receive study therapy in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 32 patients will be accrued for this study.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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 AND failed* prior therapy with anti-thymocyte

globulin and etanercept on protocol FHCRC-1872. 00 NOTE: *Failure is defined as progression or "more advanced" disease

- Not a candidate for stem cell transplantation due to any of the following reasons:

- No suitable bone marrow donor available

- Not eligible for a transplantation protocol

- Not willing to undergo transplantation

- Not eligible for enrollment on protocol FHCRC-1888. 00

- No acute myeloid leukemia (i. e., ≥ 20% blasts)

PATIENT CHARACTERISTICS:

Age

- 18 and over

Performance status

- ECOG 0-2

Life expectancy

- Not specified

Hematopoietic

- Absolute neutrophil count > 250/mm^3

- Platelet count > 100,000/mm^3

Hepatic

- AST and ALT ≤ 2 times upper limit of normal (ULN)

Renal

- Creatinine ≤ 1. 5 times ULN

Cardiovascular

- No history of or current evidence of cardiac arrhythmia

- No history of or current evidence of congestive heart failure

Pulmonary

- No pneumonia within the past 2 weeks

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No other active severe infection (e. g., septicemia or pneumonia) within the past 2

weeks

- No other severe disease that would preclude study compliance

- No known or suspected hypersensitivity to azacitidine or mannitol

PRIOR CONCURRENT THERAPY:

Biologic therapy

- See Disease Characteristics

- No prior hematopoietic stem cell transplantation

- More than 4 weeks since prior and no concurrent hematopoietic growth factors for MDS

- More than 4 weeks since prior immunomodulatory therapy for MDS

- No other concurrent immunomodulatory therapy for MDS

Chemotherapy

- No prior azacitidine

Endocrine therapy

- Not specified

Radiotherapy

- Not specified

Surgery

- Not specified

Other

- More than 2 weeks since prior cytotoxic therapy for MDS

- More than 2 weeks since prior experimental therapy for MDS

- No other concurrent cytotoxic therapy for MDS

- No other concurrent experimental therapy for MDS

Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, United States

Seattle Cancer Care Alliance, Seattle, Washington 98109-1023, United States

Clinical trial summary from the National Cancer Institute's PDQ® database

Starting date: April 2005
Last updated: May 29, 2008