Clinical Trials /

Adding Ruxolitinib to a Combination of Dasatinib Plus Dexamethasone in Remission Induction Therapy in Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Patients Aged 40 Years or Older

NCT02494882

Description:

The purpose of this study is to test the safety of a new combination of three oral drugs in Ph+ ALL. These drugs are dexamethasone, dasatinib, and ruxolitinib. All three drugs have been studied before in humans. This is a phase I study in which ruxolitinib dose will start low for the first patient together with dexamethasone plus dasatinib. If this dose does not cause a bad side effect, the ruxolitinib dose will slowly be made higher as new patients take part in the study. This will help the investigators find the right dose of ruxolitinib to give together with dexamethasone and dasatinib that will be used in future studies

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Chronic Myeloid Leukemia
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Adding Ruxolitinib to a Combination of Dasatinib Plus Dexamethasone in Remission Induction Therapy in Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Patients Aged 40 Years or Older
  • Official Title: Phase I Trial Adding Ruxolitinib to a Combination of Dasatinib Plus Dexamethasone in Remission Induction Therapy in Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Patients Aged 40 Years or Older.

Clinical Trial IDs

  • ORG STUDY ID: 14-272
  • NCT ID: NCT02494882

Conditions

  • Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
RuxolitinibAdding Ruxolitinib to Combination of Dasatinib + Dexamethasone
DasatinibAdding Ruxolitinib to Combination of Dasatinib + Dexamethasone
DexamethasoneAdding Ruxolitinib to Combination of Dasatinib + Dexamethasone

Purpose

The purpose of this study is to test the safety of a new combination of three oral drugs in Ph+ ALL. These drugs are dexamethasone, dasatinib, and ruxolitinib. All three drugs have been studied before in humans.

This is a phase I study in which ruxolitinib dose will start low for the first patient together with dexamethasone plus dasatinib. If this dose does not cause a bad side effect, the ruxolitinib dose will slowly be made higher as new patients take part in the study. This will help the investigators find the right dose of ruxolitinib to give together with dexamethasone and dasatinib that will be used in future studies

Detailed Description

Trial Arms

NameTypeDescriptionInterventions
Adding Ruxolitinib to Combination of Dasatinib + DexamethasoneExperimentalSteroid Pre-Phase (Days -6 to 0) Prednisone 10 mg/m2/day uptitrated to 60/mg/m2/day oral over seven days (capped at 120 mg/day). Remission Induction (Days 1 to 84) Dasatinib 140 mg oral once daily. Days 1-84. Dexamethasone 10 mg/m2/day oral (capped at 20 mg/day). Days 1-24. Dexamethasone oral taper 10 mg/m2/day (capped at 20 mg/day) to off. Taper days 25-32. Off day 33. Ruxolitinib phase I cohort dose oral. Days 1-84. Delivered BID. Delivered per the phase I dose cohort. Methotrexate (MTX) 12 mg Intrathecal (IT) for 4 doses on days 22, 43, 64, 85; +/- 3 days. Post-Remission Induction Therapy (Starting Day 85) Allogeneic HSCT, at the discretion of the treating physician, at any point post-remission induction. Or, post-remission induction (consolidation) therapy to be determined per the treating physician
  • Ruxolitinib
  • Dasatinib
  • Dexamethasone

Eligibility Criteria

Inclusion Criteria:

- Patient able to give informed consent.

- Precursor B-cell acute lymphoblastic leukemia Philadelphia chromosome-positive (Ph+) patients.

- Precursor B-cell lineage determined by standard flow cytometry.

- Ph+ by cytogenetics (karyotype/FISH) and/or molecular (BCR-ABL1 transcripts)

- Determined in CLIA-certified laboratory

- Previously untreated, except for below allowances in a recent diagnosis:

- Previously received HyperCVAD cycle 1A +/- cycle 1B.

- Previously received Induction Phase I +/- Induction Phase II of BFM-modeled (Pediatric or Pediatric-Inspired) ALL regimen

- Previously received other representative (modified from HyperCVAD, BFM, or AML- like) ALL induction course

- Including bcr-abl TKI plus corticosteroid

- Patients with relapsed Ph+ ALL, including both molecular and morphologic relapse.

- Patients aged > 18 with Ph-like ALL, either newly diagnosed, minimally treated, or relapsed. Ph-like ALL with mutations or rearrangements known to respond to either dasatinib or ruxolitinib will be eligible, and include fusions involving ABL1, ABL2, CSF1R and PDGFRB (for dasatinib) and EPOR, JAK2 and CRLF2 (for ruxolitinib).

- Patients with CML in lymphoid blast crisis, either untreated or relapsed.

- Acceptable end-organ function, except for documented exclusions for organ function compromise due to ALL itself

- Aged 40 years and older. Patients with newly diagnosed or minimally treated ALL younger than 40 are allowed if they are unfit to receive conventional chemotherapy.

- ECOG performance status ≤ 2

- Men and women of childbearing potential must be willing to practice an effective method of birth control during treatment and for at least 4 months following treatment on study

Exclusion Criteria:

- Ph-negative ALL

- Relapsed Ph+ ALL or patients with dominant leukemic clone bearing documented bcr-abl mutations enabling bcr-abl TKI resistance at diagnosis

- Lymphoid blast crisis of chronic myelogenous leukemia (CML)

- Mature B-cell (Burkitt's) ALL

- Clinical signs of CNS disease

- Active ALL in CNS or testes

- Serum creatinine > 1.5x ULN and calculated creatinine clearance, based on a 24-hour urine collection, < 30 mL/min--unless related to ALL/tumor lysis syndrome and able to be corrected

- Direct Bilirubin > 2x ULN; AST/ALT > 10x ULN, unless related to ALL liver infiltration.

- Pregnant women or women who are breast-feeding

- Patients with HIV, Hepatitis B, or Hepatitis C

- Pre-treatment QTcF > 480 msecs

- Active malignancy requiring treatment other than ALL within two years prior to start of treatment, with the exception of basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or DCIS or LCIS of the breast

- Active, uncontrolled infection, any other concurrent disease, or medical condition that is deemed to interfere with the conduct of the study as judged by the investigator

- Unable to tolerate anti-viral and anti- Pneumocystis jirovecii prophylaxis while on pre-phase and remission induction therapy

- Unable to tolerate gastrointestinal prophylaxis therapy with sucralfate while on pre-phase and remission induction therapy. Or severe pre-existing GI disorder that requires PPI or H2 receptor antagonist therapy be uninterrupted

Maximum Eligible Age:N/A
Minimum Eligible Age:40 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Clinical response
Time Frame:2 years
Safety Issue:
Description:is to be evaluated by using a combination of criteria. Molecular remissions will be defined by standard criteria for BCR-ABL1 and IGH qRT-PCR. Flow cytometric assessment of MRD will be defined by standard flow cytometry criteria

Secondary Outcome Measures

Measure:Complete Molecular Remission (CMR) rate
Time Frame:2 years
Safety Issue:
Description:Molecular remission status will be defined by undetectable BCR-ABL1 transcripts and/or IGH clonal gene rearrangement in bone marrow aspirate (BMA) examination as determined by qRT-PCR in CLIA laboratory.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Memorial Sloan Kettering Cancer Center

Trial Keywords

  • Ruxolitinib
  • Dasatinib
  • Dexamethasone
  • 14-272

Last Updated

February 6, 2017