Low Dose Decitabine, Low Dose Azacitidine, or Standard Dose Azacitidine in Treating Patients with Transfusion-Dependent Myelodysplastic Syndrome or Best Supportive Care in Patients with Transfusion-Independent Myelodysplastic Syndrome

This randomized phase II trial studies how well low dose decitabine, low dose azacitidine, or standard dose azacitidine works in treating patients with myelodysplastic syndrome (MDS) who need blood transfusion (transfusion-dependent) compared to best supportive care in patients with MDS who do not need blood transfusion (transfusion-independent). Drugs used in chemotherapy, such as decitabine and azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether low dose decitabine, low dose azacitidine, or standard dose azacitidine is most effective in treating or offering best supportive care for patients with myelodysplastic syndrome.

Inclusion Criteria

• Sign an Institutional Review Board (IRB)-approved informed consent document
• International Prognostic Scoring System (IPSS) low- or intermediate-1-risk MDS, including chronic myelomonocytic leukemia (CMML)-1
• Eastern Cooperative Oncology Group (ECOG) performance status of =< 3 at study entry
• Serum creatinine =< 2 mg/dL
• Total bilirubin =< 2 x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2 x ULN; aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2 x ULN
• Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days and will also need to use contraceptives; men must agree not to father a child and agree to use a condom if his partner is of child bearing potential

Exclusion Criteria

• Breast feeding females
• Prior therapy with decitabine or azacitidine

PRIMARY OBJECTIVES:

I. Compare the event-free survival rates of two different drugs: decitabine (DAC) versus azacitidine (AZA) on an abbreviated schedule to a standard arm of AZA given over 5 days in patients with low-risk MDS transfusion-dependent and to best supportive care (BSC) in patients with low-risk MDS transfusion-independent.

SECONDARY OBJECTIVES:

I. Compare the response rates for the transfusion independent and the transfusion dependent patients. For example the response rate of two different drugs DAC versus AZA on abbreviated schedule to a standard arm of AZA given over 5 days.

II. Evaluate the durability of response, the overall and transformation-free survival rates, and the safety profile of 2 different drugs.

III. The quality of life protocol (2014-0636) titled “Interventional Validation of an MDS-Specific Measure of Quality of Life: Assessing the Responsiveness of the QUALMS-1 to Different Hypomethylating Agent Regimens for Low and Intermediate Risk Disease” was written specifically as a companion study to protocol 2014-0112 and may be offered as an optional assessment to patients enrolled onto this protocol.

OUTLINE: Transfusion-dependent patients are randomized to 1 of 3 treatment arms (Arm I, Arm II, or Arm III). Transfusion-independent patients are assigned to Arm IV.

ARM I (LOW DOSE DECITABINE): Patients receive decitabine intravenously (IV) over 1 hour on days 1-3. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II (LOW DOSE AZACITIDINE): Patients receive azacitidine IV or subcutaneously (SC) on days 1-3. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM III (STANDARD DOSE AZACITIDINE): Patients receive azacitidine IV or SC on days 1-5. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM IV (SUPPORTIVE CARE): Patients receive best supportive care.

After completion of study treatment, patients are followed up every 6-12 months for up to 5 years.

Lead Organization
M D Anderson Cancer Center

Principal Investigator
Guillermo Garcia-Manero

Primary ID 2014-0112
Secondary IDs NCI-2014-02339
Clinicaltrials.gov ID NCT02269280