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 | Active Not Recruiting Phase 1

• 1 other identifier: 14-272
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Acute Lymphoblastic Leukemia

Keywords

Ruxolitinib; Dasatinib; Dexamethasone; 14-272

Outcome Measures

Primary Outcomes (1)

• Clinical response

  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

  2 years

Secondary Outcomes (1)

• Complete Molecular Remission (CMR) rate

  2 years

Study Arms (1)

Adding Ruxolitinib to Combination of Dasatinib + Dexamethasone

EXPERIMENTAL

Steroid 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

Drug: Ruxolitinib; Drug: Dasatinib; Drug: Dexamethasone

Interventions

Ruxolitinib DRUG

Adding Ruxolitinib to Combination of Dasatinib + Dexamethasone

Dasatinib DRUG

Adding Ruxolitinib to Combination of Dasatinib + Dexamethasone

Dexamethasone DRUG

Adding Ruxolitinib to Combination of Dasatinib + Dexamethasone

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient able to give informed consent.
• Patients \>/= 18 years with the following disease will be eligible
• Newly diagnosed Ph+ ALL, previously untreated, except for the below allowances
• Previously received HpyerCVAD cycle 1A+/- cycle 1B
• Previously received Induction Phase 1 +/- Induction Phase II of BFM-modeled (Pediatric of Pediatric-Inspired) ALL regimen
• Previously received other representative (modified from HyperCVAD, BFM, or AML-like) ALL induction course, including ABL TKI plus corticosteroid.
• If the patient has received any of the above prior therapy, they may be enrolled, regardless of remission status.
• Relapsed PH+ ALL, with no prior exposure to dasatinib and without known ABL kinase mutations predited to be resistant to dasatibin (e.g. L248R, L248V, Q252H, E255K, V299L, T315A, T315I, F317C, F317L, F317S, F317V)
• Relapsed or refractory Ph-like ALL without prior exposure to dasatibin and with mutations or rearrangements of genes conferring sensitivity to dasatibin (ABL, CSF1R, PDGFRB) or ruxolitinib (CRLF2, JAK3, EPOR, TSLP)
• Newly diagnosed or relapsed CML in lymphoid blast crisis
• Confirmation of Philadelphia chromosome positivity by cytogenetics (karyotype/FISH) and/or molecular tests (BCR-ABL1 transcripts)
• 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

You may not qualify if:

• Ph-negative ALL
• Patients with dominant leukemic clone bearing documented bcr-abl mutations enabling bcr-abl TKI resistance at diagnosis
• Mature B-cell (Burkitt's) ALL
• 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
• A "washout" period of at least 14 days from last previous cytotoxic chemotherapy will be required prior to starting treatment on this protocol. No "washout" period will be required for previous bcr-abl TKI therapy given with the aforementioned previous chemotherapy cycles. Hydroxyurea and corticosteroids may be given as bridge therapy up until 24 hours prior to initiating protocol treatment.
• 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, localized prostate cancer, 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

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Incyte Corporation: collaborator
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

ruxolitinib; Dasatinib; Dexamethasone

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Jae Park, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 8, 2015
• First Posted: July 10, 2015
• Study Start: June 29, 2015
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: July 2, 2025

Record last verified: 2025-07

Locations

US (1)