Sapanisertib in Treating Patients With Relapsed and/or Refractory Acute Lymphoblastic Leukemia

• Status: Active, not recruiting
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)

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