A Phase I Study Investigating the Combination of Cladribine, Low Dose Cytarabine and Sorafenib Alternating With Decitabine in Pediatric Relapsed and Refractory Acute Leukemias

Inclusion Criteria

• •1. Age ≥ 1 year to 21 years
• •2. ECOG performance status of ≥ 2.
• •3. Relapsed21/refractory: AML22 or Mixed phenotype acute leukemia (MPAL) patients /Acute leukemia of ambiguous lineage (ALAL) with.
• •1. ≥1% leukemic blasts in the bone marrow:
• •2. As detected by MRD testing ≥ 25% or MRD is ≥ 5% with 1 additional sensitive diagnostic test demonstrating .1% blasts (NGS-MRD (clonoSeq23) or FISH or cytogenetics or RT-PCR of leukemic specific marker or M2/M3 morphology); or MRD is ≥ 1% with 2 additional sensitive diagnostic tests demonstrating ≥1% blasts.
• •i. If the MRD is ≥ 1% but without the required confirmatory tests, then a relapse can still be defined if a consecutive marrow evaluation separated by ≥1 week demonstrates. ≥ 1% using 2 sensitive diagnostic tests.
• •ii. If MRD testing is unavailable, then a single marrow is sufficient to define relapse if M3 morphology or M2 morphology with 1 additional sensitive diagnostic test demonstrating ≥1% blasts (FISH or cytogenetics or RT-PCR of leukemic specific marker) or M1 morphology with 2 additional sensitive diagnostic tests demonstrating. ≥1% blasts is present.
• •iii. If the morphology is M2 with no confirmatory tests, then a relapse can still be defined if a consecutive marrow evaluation separated by ≥ 1 week demonstrates M2 morphology.
• •c. Marrow definitions: M2 marrow ≥ 5 to \<25% blasts; M3 marrow ≥ 25% blasts
• •4. WBC must be below 25,000/ ƒÊL at time of enrollment. Patients may receive cytoreduction prior to enrollment.
• •5. Baseline ejection fraction must be \> 40%.
• •6. Adequate hepatic function (direct bilirubin \< 1.5x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement, and AST and/or ALT \< 5x ULN unless considered due to leukemic involvement, in which case direct bilirubin or AST and/or ALT \< 5x ULN will be considered eligible).
• •7. Adequate renal function (creatinine clearance ≥ 30 mL/min) unless related to disease. (Justification on page 7-8)
• •8. In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 14 days for cytotoxic or non-cytotoxic (immunotherapy agent(s), or an interval of 5 half-lives of the prior therapy. Oral hydroxyurea and/or cytarabine (up to 2 g/m2) for patients with rapidly proliferative disease is allowed before the start of study therapy, as needed, for clinical benefit and after discussion with the PI. Concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted.
• •9. Unless surgically or biologically sterile: Women of childbearing potential must agree to adequate methods of contraception during the study and at least 3 months for males, and 6 months for females, after the last treatment.