Protocol Summary

Protocol No.: OCR15238

Sponsor Protocol No.: 18424-269; AALL1521

Study Title
A Phase 2 Study of the JAK1/JAK2 Inhibitor Ruxolitinib With Chemotherapy in Children With De Novo High-Risk CRLF2-Rearranged and/or JAK Pathway-Mutant Acute Lymphoblastic Leukemia

Principal Investigator(s)
Slayton, William

This is a nonrandomized study of ruxolitinib in combination with a standard multi-agent chemotherapy regimen for the treatment of B-cell acute lymphoblastic leukemia. Part 1 of the study will optimize the dose of study drug (ruxolitinib) in combination with the chemotherapy regimen. Part 2 will evaluate the efficacy of combination chemotherapy and ruxolitinib at the recommended dose determined in Part 1.

Phase: Phase II

Age Group: Both

Scope: National

In Part 1, ruxolitinib will be administered at a protocol-defined starting dose in combination with chemotherapy, with dose escalation and de-escalation following the rolling 6 study design. The established recommended starting dose will be taken forward into Part 2.

Detailed Eligibility
1. Ages 1 to 21 years of age
2. De novo high-risk (HR) Ph-like B-ALL for which any of following criteria are present at diagnosis:
- Age >= 10 years
- White blood cell (WBC) >= 50 × 10^3/μL
- CNS3 leukemia
3. One of the following Ph-like ALL genetic lesions must be present in the diagnostic bone marrow or peripheral blood sample:
- CRLF2 rearrangement with JAK1 or JAK2 mutation (JAK+)
- CRLF2 rearrangement without JAK mutation
- Other JAK pathway alterations (eg, JAK2 fusions, erythropoietin receptor (EPO-R) fusions, SH2B3 deletions, interleukin-7 receptor-alpha (IL7RA) mutations) with or without CRLF2 rearrangement
4. Completed a 4-drug Induction therapy regimen (modified aBFM regimen or equivalent) in Study AALL1131 or as the institutional standard of care for HR B-ALL and have had end-Induction minimal residual disease (MRD) assessed
5. Male and female subjects of reproductive non childbearing potential or willing to take appropriate precautions to avoid pregnancy or fathering a child for the duration of study participation

1. Receipt of any other cytotoxic chemotherapy before Induction therapy, with exception of hydroxyurea or steroid pretreatment
2. Trisomy 21 (Down syndrome)
3. BCR-ABL1-rearranged (Ph+) ALL
4. Calculated creatinine clearance or radioisotope glomerular filtration rate 5. Alanine aminotransferase ≥ 3 × upper limit of normal (ULN) for age
6. Direct bilirubin ≥ 1.5 × ULN (may be assumed if total bilirubin is below ULN)
7. History or evidence of cirrhosis
8. Platelet count 9. Absolute neutrophil count (ANC) 10. Positive screen for hepatitis B or C
11. Known human immunodeficiency virus infection

Applicable Disease Sites
Pediatric (Childhood) Cancer

Participating Institutions
UF Gainesville : Heather Rogers

Heather Rogers, RN
Phone: +1 352-294-8743


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