Ruxolitinib Phosphate or Dasatinib With Chemotherapy in Treating Patients With Relapsed or Refractory Philadelphia Chromosome-Like Acute Lymphoblastic Leukemia
Condition: Recurrent B Acute Lymphoblastic Leukemia; Recurrent Ph-Like Acute Lymphoblastic Leukemia; Refractory B Acute Lymphoblastic Leukemia; Refractory Ph-Like Acute Lymphoblastic Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Recurrence; Philadelphia Chromosome
Intervention: Cyclophosphamide; Cytarabine; Dasatinib; Dexamethasone; Doxorubicin; Laboratory Biomarker Analysis; Leucovorin; Mercaptopurine; Methotrexate; Prednisone; Rituximab; Ruxolitinib Phosphate; Vincristine
Intervention description: Given IV; Given IV; Given PO; Given PO or IV; Given IV; Correlative studies; Given IV or PO; Given PO; Given IV and PO; Given PO; Given IV; Given PO; Given IV
Intervention MeSH terms: Leucovorin; Cytarabine; Dexamethasone; Dexamethasone acetate; Prednisone; Cortisone; Cyclophosphamide; Rituximab; Doxorubicin; Liposomal doxorubicin; Methotrexate; Vincristine; Daunorubicin; Dasatinib; Mercaptopurine; Antineoplastic Agents, Immunological; Antibodies; Immunoglobulins; Antibodies, Monoclonal; BB 1101
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 10 Years
Healthy volunteers: No

Summary:

      This phase II trial studies the side effects and best dose of ruxolitinib phosphate and how
      well it works compared to dasatinib when given with chemotherapy in treating patients with
      Philadelphia chromosome-like acute lymphoblastic leukemia that has come back (relapsed) or
      has not responded to treatment (refractory). Ruxolitinib phosphate and dasatinib may stop the
      growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in
      chemotherapy work in different ways to stop the growth of cancer cells, either by killing the
      cells, by stopping them from dividing, or by stopping them from spreading. It is not yet
      known whether giving ruxolitinib phosphate or dasatinib with chemotherapy works better in
      treating patients with previously treated acute lymphoblastic leukemia.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with previously treated B-cell ALL (relapsed and/or refractory after prior
             therapy)

          -  Bone marrow involvement with >= 5% lymphoblasts

          -  Documented genetic lesion(s) known to confer susceptibility to inhibition by either
             ruxolitinib or dasatinib or cytokine receptor-like factor 2 (CRLF2) positivity by flow
             cytometry (for the ruxolitinib cohort)

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  Total bilirubin < 2.0 mg/dL

          -  Serum glutamate pyruvate transaminase (SGPT) or serum glutamic oxaloacetic
             transaminase (SGOT) < 3 x upper limit of normal (ULN)

          -  Creatinine < 2 mg/dL

          -  Females of childbearing potential must have a negative serum or urine beta human
             chorionic gonadotropin (beta-hCG) pregnancy test result within 14 days prior to the
             first dose of study drugs and must agree to use an effective contraception method
             during the study and for 30 days following the last dose of study drug; females of
             non-childbearing potential are those who are postmenopausal greater than 1 year or who
             have had a bilateral tubal ligation or hysterectomy; appropriate methods of birth
             control include the following: any 2 of the following methods used together: birth
             control implants, injections, or pills (except for progesterone only pills),
             intrauterine device (IUD), vasectomy, tubal ligation, barrier method (female or male
             condom with spermicide, cervical cap with spermicide, diaphragm with spermicide); male
             condom with spermicide and diaphragm; male condom with spermicide and cervical cap;
             unacceptable methods of birth control include using no birth control, withdrawal,
             rhythm method, vaginal sponge, any barrier method that does not use spermicide,
             progesterone only pills, and using male and female condoms at the same time

          -  Males who have partners of childbearing potential must agree to use an effective
             contraceptive method during the study and for 30 days following the last dose of study
             drug

          -  Patients or their legally authorized representative must provide written informed
             consent

        Exclusion Criteria:

          -  Burkitt's leukemia or lymphoma, T-cell ALL or lymphoblastic lymphoma

          -  Patients having undergone prior allogeneic stem cell transplant within 3 months or
             having active graft versus host disease

          -  Patient is pregnant or breastfeeding

          -  Patients with uncontrolled active infections (fever >= 38 degrees Celsius [C], septic
             shock)

          -  Isolated extramedullary relapse (i.e. testicular, central nervous system)

          -  Current or chronic hepatitis B or C infection, or known seropositivity for human
             immunodeficiency virus (HIV)

          -  Concurrent chemotherapy (except intrathecal chemotherapy)

          -  Major surgery within 4 weeks prior to first study dose

          -  Systemic chemotherapy/radiotherapy/investigational therapy within 14 days (with the
             exception of hydroxyurea and steroids) prior to starting therapy; for patients
             receiving ALL maintenance with 6-mercaptopurine, methotrexate, vincristine, and
             steroids - these agents should be discontinued at least 48 hours prior to start of
             study drugs; for patients on oral targeted therapies (such as imatinib, dasatinib,
             ponatinib), - these agents should be discontinued at least 48 hours prior to start of
             study drugs

          -  Patients must have recovered from acute non hematologic toxicity (to =< grade 1) of
             all previous therapy prior to enrollment

          -  Known active central nervous system (CNS) leukemia, as defined by unequivocal
             morphologic evidence of lymphoblasts in the cerebrospinal fluid (CSF), use of
             CNS-directed local treatment for active disease within the prior 28 days, symptomatic
             CNS leukemia (i.e., cranial nerve palsies or other significant neurologic dysfunction)
             within 28 days; patients may have history of CNS leukemic involvement if definitively
             treated with prior therapy and no evidence of active disease (defined as >= 2
             consecutive spinal fluid assessments with no evidence of disease) at the time of
             registration; prophylactic intrathecal chemotherapy is not a criterion for exclusion

          -  Patients with active heart disease (New York Heart Association [NYHA] class 3-4 as
             assessed by history and physical examination, unstable angina/stroke/myocardial
             infarction within the last 6 months)

          -  Patients with a cardiac ejection fraction (as measured by either multi-gated
             acquisition [MUGA] scan or echocardiogram) < 40%; (Note: patients who have had prior
             anthracycline exposure of > 250 mg/m^2 may be eligible after discussion with the
             principal investigator [PI])

          -  Second malignancy other than basal cell or squamous cell carcinoma of the skin or in
             situ carcinoma of the cervix or the breast, unless they are successfully treated with
             curative intent for more than 2 years before entering the study

          -  Malabsorption syndrome or other conditions that preclude enteral route of
             administration

          -  Patients requiring strong cytochrome P450, family 3, subfamily A, polypeptide 4
             (CYP3A4) inhibitors

          -  Other severe acute or chronic medical or psychiatric condition or laboratory
             abnormality that in the opinion of the investigator may increase the risk associated
             with study participation or investigational product administration or may interfere
             with the interpretation of study results and/or would make the patient inappropriate
             for enrollment into this study