Low-dose Oral Clofarabine for the Treatment of IPSS INT-1, INT-2 or HIGH Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia

This is an interventional treatment trial for Cancer focused on measuring hypomethylating therapy, CML, myelodysplastic syndromes Read More

Inclusion Criteria:

A bone marrow biopsy confirmed diagnosis of MDS or CMML (dysplastic subtype) according to WHO criteria within 2 weeks of registration.

1. Patients must have an International Prognostic Scoring System (IPSS), see Appendix D, score of INT-1 or higher at study entry.35 Patients with an IPSS score of INT-1 with the 5q- deletion should have failed Lenalidomide therapy and should have more than 5% blasts in the bone marrow or a platelet count < 50,000/mm3 or an absolute neutrophil count < 500/mm3 or be requiring therapy (e.g. being transfusion dependent). Patients with CMML must have a WBC < 12,000/mm3 documented within 4 weeks prior to study entry (two sets of counts that are 2 weeks apart will be taken).
2. Patients with MDS should have failed or relapsed after treatment with one regimen of hypomethylating agents (5-Azacytidine or Decitabine) but no more than 2 prior therapies including only 1 hypomethylating agent... Patients with CMML (dysplastic subtype) may be enrolled even if they have not received any prior therapy.
3. Untreated patients who are ineligible for or unwilling to undergo hypomethylating agent therapy can be enrolled
4. Age ≥ 18 years.
5. Patients must have and ECOG performance status of 0 - 2.
6. Provide signed written informed consent.

7. Have adequate renal and hepatic functions as indicated by the following laboratory values:

   • Serum creatinine 1.0 mg/dL; if serum creatinine 1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be 30 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation where Predicted GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine)-1.154 x (age in years)-0.023 x (0.742 if patient is female) x (1.212 if patient is black)
   • Serum bilirubin ≤1.5 mg/dL × upper limit of normal (ULN)
   • Aspartate transaminase (AST)/alanine transaminase (ALT) 2.5 × ULN
   • Alkaline phosphatase 2.5 × ULN
8. Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent.
9. Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment.
10. Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment

Exclusion Criteria:

1. Current concomitant chemotherapy, radiation therapy, or immunotherapy other than as specified in the protocol.
2. Pre-treatment with more than 2 previous regimens.
3. Use of investigational agents within 30 days or any anticancer therapy within 30 days before study entry with the exception of hydroxyurea. The patient must have recovered from all acute toxicities from any previous therapy.
4. Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo treatment.
5. Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
6. Pregnant or lactating patients.
7. Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.