Expired Study
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New York, New York 10065


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


Criteria:

Inclusion Criteria: - 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) - Acceptable end-organ function, except for documented exclusions for organ function compromise due to ALL itself - 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 - 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


Study is Available At:


Original ID:

14-272


NCT ID:

NCT02494882


Secondary ID:


Study Acronym:


Brief Title:

Adding Ruxolitinib to a Combination of Dasatinib Plus Dexamethasone in Remission Induction Therapy in Newly Diagnosed Philadelphia Chromosome-Positive


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.


Overall Status:

Active, not recruiting


Study Phase:

Phase 1


Genders:

N/A


Minimum Age:

40 Years


Maximum Age:

N/A


Quick Facts

Healthy Volunteers
Oversight Has DMC
Study Is FDA Regulated
Study Is Section 801
Has Expanded Access

Study Source:

Memorial Sloan Kettering Cancer Center


Oversight Authority:

United States: Food and Drug Administration


Reasons Why Stopped:


Study Type:

Interventional


Study Design:


Number of Arms:

1


Number of Groups:

0


Total Enrollment:

12


Enrollment Type:

Actual


Overall Contact Information

Official Name:Jae Park, MD
Principal Investigator
Memorial Sloan Kettering Cancer Center

Study Dates

Start Date:June 29, 2015
Completion Date:June 2020
Completion Type:Anticipated
Primary Completion Date:June 2020
Primary Completion Type:Anticipated
Verification Date:February 2019
Last Changed Date:February 8, 2019
First Received Date:July 8, 2015

Study Outcomes

Outcome Type:Primary Outcome
Measure:Clinical response
Time Frame:2 years
Safety Issues:False
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
Outcome Type:Secondary Outcome
Measure:Complete Molecular Remission (CMR) rate
Time Frame:2 years
Safety Issues:False
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.

Study Interventions

Intervention Type:Drug
Name:Ruxolitinib
Arm Name:Adding Ruxolitinib to Combination of Dasatinib + D
Intervention Type:Drug
Name:Dasatinib
Arm Name:Adding Ruxolitinib to Combination of Dasatinib + D
Intervention Type:Drug
Name:Dexamethasone
Arm Name:Adding Ruxolitinib to Combination of Dasatinib + D

Study Arms

Study Arm Type:Experimental
Arm Name:Adding Ruxolitinib to Combination of Dasatinib + Dexamethasone
Description: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

Study Agencies

Agency Class:Other
Agency Type:Lead Sponsor
Agency Name:Memorial Sloan Kettering Cancer Center
Agency Class:Industry
Agency Type:Collaborator
Agency Name:Incyte Corporation

Sample and Retention Information

There are no available Sample and Retention Information

Study References

There are no available Study References

Data Source: ClinicalTrials.gov

Date Processed: January 21, 2020

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