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

Objective
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

Treatment
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
INCLUSION CRITERIA:
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

EXCLUSION CRITERIA:
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
Leukemia
Pediatric (Childhood) Cancer

Participating Institutions
UF Gainesville : Heather Rogers

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

Email: heatherrogers@ufl.edu

More Information:
View study listing on ClinicialTrials.gov
http://www.clinicaltrials.gov/ct2/show/
NCT02723994