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Ruxolitinib and Chemotherapy in Adolescents and Young Adults With Ph-like Acute Lymphoblastic Leukemia

ConditionsAcute Lymphoblastic LeukemiaALL, ChildhoodALL
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-39
SponsorUniversity of Chicago

About this trial

This study will test if adding ruxolitinib to standard multi-drug chemotherapy regimen will be safe and tolerated in adolescents and young adults with newly diagnosed Ph-like acute lymphoblastic leukemia (ALL).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Newly diagnosed de novo B-precursor acute lymphoblastic leukemia (ALL) as determined by World Health Organization (WHO) criteria. Patients must have unequivocal diagnosis of precursor B ALL. This includes an institutional immunophenotyping report that is to assign B-lineage or T-lineage.

"Ph-like" signature, as determined by low density micro-array (LDA) card

Cytokine receptor-like factor 2 (CRLF2) rearranged (JAK2 mutant or wild-type)

JAK2 or erythropoietin receptor (EPOR) fusions.

Disqualifiers

Patients who are receiving any other investigational agent.

Patients with a "currently active" second malignancy other than non-melanoma skin cancers. Patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for ≥ 3 years.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib or other agents used in study.

Use of any potent cytochrome P450 (CYP) 3A4 inhibitor or inducer within 5 half-lives before the first dose of the study drug. Potent inhibitors of CYP3A4 include systemic ketoconazole, posaconazole, voriconazole, clarithromycin, itraconazole, nefazodone, and telithromycin. At the fluconazole dose of 200mg daily used this regimen, there is minimal inhibition of CYP3A4 [36] and therefore fluconazole is not prohibited on this trial and no dose modifications should be made in the presence of fluconazole.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Ruxolitinib

    Drug

    Participants will receive one of 3 doses \[taken by mouth\] (30 mg, 40 mg, or 50 mg) depending on when they are enrolled to the study. Remission consolidation regimen: * Days 1-14 and 29-43 Interim maintenance regimen: * Days 1-14 and 29-43 Delayed Intensification regimen: * Days 1-14 and 29-43

  • Cyclophosphamide

    Drug

    Remission consolidation regimen: * 1000 mg/m2 by intravenous infusion (IV) on Day 1 and Day 29 Delayed Intensification regimen: * 1000 mg/m2 IV on Day 29

  • Cytarabine

    Drug

    Remission consolidation regimen: * 75 mg/m2/day IV or subcutaneously (SC) on Days 1-4 (i.e., 4 doses), 8-11, 29-32, and 36-39 Delayed Intensification regimen: * 75 mg/m2/day IV or SC on Days 29-32 and 36-39

  • Mercaptopurine

    Drug

    Taken by mouth. Remission consolidation regimen: * 60 mg/m2 on Days 1-14 and 29-42 Maintenance Therapy: * 75 mg/m2 on Days 1-84

  • Vincristine

    Drug

    Remission consolidation regimen: * 1.5 mg/m2 (maximum 2 mg) IV once per week on Days 15, 22, 43, and 50 Interim maintenance regimen: * 1.5 mg/m2 (maximum 2 mg) IV on Days 1, 11, 21, 31, and 41 Delayed Intensification regimen: * 1.5 mg/m2 (maximum 2 mg) IV on Days 1, 8, 15, 43, and 50 Maintenance Therapy: * 1.5 mg/m2 (maximum 2 mg) IV on Days 1, 29, and 57

  • Pegaspargase

    Drug

    Remission consolidation regimen: * 2500 IU/m2 given by intramuscular (IM) injection or IV on Days 15 and 43 Interim maintenance regimen: * 2500 IU/m2 IM or IV on Days 2 and 22 Delayed Intensification regimen: * 2500 IU/m2 IM or IV on Day 4 (OR Day 5 OR Day 6) AND Day 43.

  • Rituximab

    Drug

    For patients that have cluster of differentiation antigen 20 positive (CD20+) disease only. Remission consolidation regimen: * 375 mg/m2 IV on Days 1, 8, 29 and 36 Interim maintenance regimen: * 375 mg/m2 IV on Days 1 and 11 Delayed Intensification regimen: * 375 mg/m2 IV on Days 1 and 8

  • Methotrexate (Intrathecal Administration)

    Drug

    Drug is given through a needle which is inserted in one of the spaces between the bones in the lower back (intrathecal \[IT\] administration). Remission consolidation regimen: * 15 mg on Days 1, 8, 15, and 22 Interim maintenance regimen: * 15 mg on Days 1 and 31 Delayed Intensification regimen: * 15 mg on Days 1, 29, and 36 Maintenance Therapy: * 15 mg on Day 1 * 15 mg on Day 29 (First 4 courses only)

  • Methotrexate (Intravenous Administration)

    Drug

    Interim maintenance regimen: * 100 mg/m2 IV on Days 1, 11, 21, 31, and 41

  • Dexamethasone

    Drug

    Taken by mouth or given by IV infusion. Delayed Intensification regimen: * 10 mg/m2 per day (divided into 2 doses) on Days 1-7 and 15-21 Maintenance Therapy: * 6 mg/m2 per day (divided into 2 doses) on Days 1-5, 29-33, and 57-61

  • Doxorubicin

    Drug

    Delayed Intensification regimen: * 25 mg/m2 IV on Days 1, 8, 15

  • Thioguanine

    Drug

    Taken by mouth at least 1 hour after evening meal. Delayed Intensification regimen: * 60 mg/m2 on Days 29-42

  • Methotrexate Oral Product

    Drug

    Taken by mouth. Maintenance Therapy: * 20 mg/m2 weekly (on Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78) * Not given on Day 29 of first 4 courses (on days when IT Methotrexate is given\]

Treatment groups

15 Participants
are divided into 1 treatment group
Group A: RuxolitinibExperimental treatment 13 interventions

Trial outcomes

Primary outcomes

1

Feasibility of adding ruxolitinib to a standard-of-care pediatric-based chemotherapy regimen in adolescents and young adult patients as determined by rate of side effects seen when combination is given

Determined by rate of side effects seen when combination is given

Time frame
24 weeks

Secondary outcomes

1

Rate of participants that are minimal residual disease (MRD) negative at end of induction therapy

Time frame
4 weeks
2

Overall survival rate

Time frame
2 years
3

Event-free survival rate

Time frame
2 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

University of Chicago

Lead sponsor

Incyte Corporation

Collaborator

Source ClinicalTrials.gov
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