Clinical Trial 19080

Cancer Type:
Interventions:MLN0128; TAK-228 (MLN0128)

Study Type: Treatment
Phase of Study: Phase II

  • Bijal Shah


Study Title

A Phase II Study of MLN0128 (TAK-228) in Relapsed and/or Refractory Acute Lymphoblastic Leukemia (ALL)


This phase II trial studies how well mTOR complex 1 and 2 (TORC1/2) Inhibitor INK128 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). TORC1/2 Inhibitor INK128 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.


Primary Objective: To determine the CR/CRi rate when MLN0128 (TAK-228) is administered to adult patients with relapsed/refractory ALL

Inclusion Criteria

  • World Health Organization (WHO)-defined acute lymphoblastic leukemia and either: A.) Relapsed after achieving remission (Patients age 59 and younger may have had up to two prior induction regimens (where the cyclophosphamide/vincristine/daunorubicin/dexamethasone and high-dose methotrexate/cytarabine cycles of hyper-cyclophosphamide/dexamethasone/doxorubicin/vincristine [CVAD] are counted as one regimen) or Patients age 60 and older may have had up to one prior induction regimen. B.) Refractory to front line therapy. C.) 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
  • 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 prior to initiation of therapy
  • Bone marrow blasts of at least 10%
  • Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2
  • Life expectancy of less than 2 months
  • Total bilirubin less than or equal to 1.5 × institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) less than or equal to 2.5 × institutional upper limit of normal
  • Creatinine less than or eqal to 1.5 × institutional upper limit of normal
  • Relapse after stem cell transplantation (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; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while she is participating in this study, she should inform her treating physician immediately; men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of MLN0128 administration
  • Ability to understand and the willingness to sign a written informed consent document
  • Prior therapy with mTOR inhibitors except for rapalog treatment as part of graft-versus-host (GVH) prophylaxis or treatment

  • Exclusion Criteria

  • Patients who have had chemotherapy or radiotherapy less than or equal to 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
  • Are receiving any other investigational agents
  • 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
  • Because of the low potential for interaction with agents that induce or inhibit cytochrome P450 enzymes, 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, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Human Immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy