Sapanisertib in Treating Patients With Relapsed and/or Refractory Acute Lymphoblastic Leukemia
Condition: B Acute Lymphoblastic Leukemia; B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; B Acute Lymphoblastic Leukemia, Philadelphia Chromosome Negative; Recurrent Adult Acute Lymphoblastic Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; T Acute Lymphoblastic Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Philadelphia Chromosome
Intervention: Laboratory Biomarker Analysis; Pharmacological Study; Sapanisertib
Intervention description: Correlative studies; Correlative studies; Given PO
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 16.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well sapanisertib works in treating patients with acute
      lymphoblastic leukemia that has returned after a period of improvement (relapsed) or has not
      responded to previous treatment (refractory). Sapanisertib may stop the growth of cancer
      cells by blocking some of the enzymes needed for cell growth.
    

Eligibility criteria:

        Inclusion Criteria:

          -  World Health Organization (WHO)-defined acute lymphoblastic leukemia and either:

               -  Relapsed after achieving remission

               -  Refractory to therapy

               -  Newly diagnosed and ineligible for intensive chemotherapy induction Note:
                  patients with T lineage and B lineage ALL are eligible for this trial; likewise,
                  patients with Philadelphia chromosome positive (Ph+) (as long as they are not
                  candidate for other therapies for Ph+) and Ph- ALL are eligible

          -  Bone marrow blasts of at least 10%

          -  At least 4 weeks away from any previous antineoplastic or investigational agent;
             patients may receive hydroxyurea or glucocorticoids for suppression of leukocytosis,
             but these must be stopped at least 24 hours (h) prior to initiation of therapy

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  Life expectancy of > 2 months

          -  Total bilirubin =< 1.5 x institutional upper limit of normal

          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 x institutional upper limit of normal

          -  Creatinine =< 1.5 x institutional upper limit of normal

          -  Fasting blood glucose (FBG) < 130 mg/dL

          -  Hemoglobin A1C (HbA1C) < 7.0%

          -  Relapse after SCT is allowed but no active graft-versus-host disease (GVHD) as per
             treating physician; also must not exceed the number of prior induction regimens listed
             above; SCT does not count as line of therapy

          -  Negative serum pregnancy test result; Note: women of child-bearing potential and men
             must agree to use 1 highly effective method of contraception and 1 additional
             effective (barrier) method, at the same time, from the time of signing the informed
             consent through 90 days (or longer, as mandated by local labeling [e.g. United States
             product insert (USPI), Summary of Product Characteristics (SmPC), etc]) after the last
             does of study drug; should a woman become pregnant or suspect she is pregnant while
             she or her partner is participating in this study, she should inform her treating
             physician immediately; men treated or enrolled on this protocol must also agree to use
             highly effective barrier contraception prior to the study, for the duration of study
             participation, and 4 months after completion of MLN0128 (TAK-228) administration

          -  Ability to understand and the willingness to sign a written informed consent document

          -  No prior therapy with mTOR inhibitors except for rapalog treatment as part of
             graft-versus-host (GVH) prophylaxis or treatment

          -  Human immunodeficiency virus (HIV) infected patients (if HIV positive)

               -  HIV infected individuals are eligible provided they meet all the protocol
                  eligibility criteria in addition to the following:

                    -  No history of acquired immune deficiency syndrome (AIDS) defining illness
                       other than a historic CD4+ T-cell nadir < 200/mm^3

                    -  Prior to leukemia diagnosis, the HIV disease was uncomplicated as evidenced
                       by:

                         -  The CD4+ T-cell counts were generally in excess of 300/mm^3

                         -  The HIV viral loads were less than 200 copies/ml if on anti-HIV therapy

                         -  If the HIV is newly diagnosed or there is no history of using anti-HIV
                            therapy, there are no AIDS defining conditions or other HIV-related
                            symptoms

                         -  Zidovudine is not allowed as part of the anti-HIV therapy

          -  Patients with diabetes controlled by diet or medication are allowed on trial;
             controlled diabetes is defined as FBG < 130 mg/kL in the context of this study

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy =< 4 weeks prior to entering the
             study or those who have not recovered from adverse events due to agents administered
             more than 4 weeks earlier; treatment with glucocorticoids, hydroxyurea, and tyrosine
             kinase inhibitors is allowed up to 24 hour prior to initiation of therapy

          -  Patients with white blood cell (WBC) > 30,000 are not eligible to start therapy;
             however, it is permissible to use glucocorticoids and/or hydroxyurea to diminish
             peripheral WBC to less than 30,000 provided these agents are stopped at least 24 hours
             prior to the first dose of MLN0128 (TAK-228)

          -  Patients who are receiving any other investigational agents

          -  Patients with known other active cancers; skin cancers (basal or squamous) are
             exempted

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to MLN0128 (TAK-228)

          -  There are no prohibitions of specific medications on the basis of anticipated
             drug-drug interactions

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, hypertension, unstable angina
             pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would
             limit compliance with study requirements; no ischemic myocardial or cerebrovascular
             event, placement of pacemaker, or pulmonary embolism within six months of receiving
             first dose of MLN0128 (TAK-228)

          -  Any patient receiving chronic corticosteroid administration prior to study enrollment
             is ineligible

          -  Baseline prolongation of the rate-corrected QT interval (QTc) > 480 milliseconds or
             history of congenital long QT syndrome or Torsades de pointes

          -  Concomitant administration of any proton pump inhibitor (PPI) is not permitted during
             the study; patients receiving PPI therapy before enrollment must stop using the PPI
             for 7 days before their first dose of study drugs