Phase I/II Study of Nilotinib/Ruxolitinb Therapy for TKI Resistant Ph-Leukemia

Sponsor
University Health Network, Toronto
Study ID
NCT01914484
Phase
PHASE1/PHASE2
Status
Completed

Conditions

  • Accelerated Phase Chronic Myeloid Leukemia
  • Blastic Phase Chronic Myeloid Leukemia
  • Chronic Phase Chronic Myeloid Leukemia
  • Philadelphia Positive Acute Lymphoblastic Leukemia
  • Resistant to Tyrosine Kinase Inhibitor Therapy

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Nilotinib — DRUG
    Nilotinib dose will remain fixed at 400mg bid throughout the cycles. BCR-ABL kinase inhibitor
  • Ruxolitinib — DRUG
    In the phase I part of the study, dose escalation will follow a 3+3 study design at either of 3 fixed dose levels (10 mg bid, 15 mg bid or 20 mg bid). No intra-patient dose-escalation will occur. JAK inhibitor

Study Details

This is the study to test combination regimen of Nilotinib and Ruxolitinib therapy for the treatment of patients with Philadelphia positive chronic myeloid leukemia (CML) or acute lymphoblastic leukemia (ALL) who is resistant to multiple tyrosine kinase inhibitor therapies with BCR-ABL kinase inhibition activity. Ruxolitinib is a tyrosine kinase inhibitor blocking alternative pathway independent of BCR-ABL mediated pathway, thus having a potential to overcome tyrosine kinase inhibitor resistance in Philadelphia positive CML or ALL patients. Phase I study will be conducted to define a recommended phase II dose (RPTD) and phase II study will examine the hypothesis that combinational approach will increase response rate of resistant CML/ALL patients, thus evaluating efficacy of the combination regimen.

Key Dates

Start date
Aug 1, 2013
Status verified
Oct 2020
Primary completion
Dec 31, 2018
Completion
Dec 31, 2018

Study Design

Enrollment
4 participants (actual)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Nilotinib with Ruxolitinib
    Nilotinib: Given that recommended dose of Nilotinib for imatinib failed CML patients is 400mg twice daily, Nilotinib dose will remain fixed at 400mg bid throughout the cycles. Ruxolitinib: In the phase I part of the study, dose escalation will follow a 3+3 study design. Dose modifications will not occur, as the purpose of this study is to determine the maximum tolerated dose. Ruxolitinib will be given at one of 3 fixed dose levels for the duration of their treatment, either 10mg twice daily, 15mg twice daily or 20mg twice daily.

Primary Outcome Measure

Phase I: Maximum Tolerated Dose (MTD) [ Time Frame: Average of 6 months ]

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