Sapanisertib in Treating Patients With Relapsed and/or Refractory Acute Lymphoblastic Leukemia
A Phase 2 Study of MLN0128 (TAK-228) in Relapsed and/or Refractory Acute Lymphoblastic Leukemia (ALL)
5 other identifiers
interventional
16
1 country
14
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_2
Started Apr 2017
Longer than P75 for phase_2
14 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 26, 2015
CompletedFirst Posted
Study publicly available on registry
June 29, 2015
CompletedStudy Start
First participant enrolled
April 6, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 28, 2018
CompletedResults Posted
Study results publicly available
May 24, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
March 5, 2024
CompletedMarch 3, 2025
February 1, 2025
1.7 years
June 26, 2015
August 11, 2021
February 11, 2025
Conditions
Outcome Measures
Primary Outcomes (1)
Complete Response (CR or CRi)
Complete response rate, defined to be a complete hematologic response (CR) or complete response incomplete (CRi) noted as the objective status at any time during treatment. A CR is defined as having less than 5% blasts in a non-hypocellular marrow with a granulocyte count of 1 x109/L (or above), and a platelet count of 100 x109/L (or higher) and absence of peripheral blood blasts with complete resolution of any extra medullary disease. A patient is defined as having a CRi if they meet all CR criteria except for residual neutropenia (ANC\<1 x109/L) or thrombocytopenia (platelets\<100 x109/L). A CR or CRi will be considered synonymous with "success". The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Ninety-five percent exact binomial confidence intervals for the true success proportion will be calculated.
61 days
Secondary Outcomes (5)
Overall Response
61 days
Duration of Complete Response
0 days
Frequency of Proceeding to Allogeneic Stem Cell Transplantation (SCT) After Achieving Response (Complete Hematologic Response [CR]/Complete Response Incomplete [CRi] Partial Response [PR], or Morphologic Leukemia Free State [MLFS]) to Sapanisertib
0 days
Overall Survival
23 months
Incidence of Adverse Events, Measured Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4
91 days
Study Arms (1)
Treatment (sapanisertib)
EXPERIMENTALPatients receive sapanisertib PO daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients who are non-responders and in PR at the end of course 4 may receive sapanisertib PO daily on days 1-28. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions
Given PO
Eligibility Criteria
You may qualify if:
- 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
- +11 more criteria
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (14)
Mayo Clinic Hospital in Arizona
Phoenix, Arizona, 85054, United States
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259, United States
City of Hope Comprehensive Cancer Center
Duarte, California, 91010, United States
Los Angeles General Medical Center
Los Angeles, California, 90033, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, 90033, United States
MedStar Georgetown University Hospital
Washington D.C., District of Columbia, 20007, United States
Mayo Clinic in Florida
Jacksonville, Florida, 32224-9980, United States
Moffitt Cancer Center
Tampa, Florida, 33612, United States
University of Kansas Clinical Research Center
Fairway, Kansas, 66205, United States
University of Kansas Cancer Center
Kansas City, Kansas, 66160, United States
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
Mayo Clinic in Rochester
Rochester, Minnesota, 55905, United States
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210, United States
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112, United States
Related Publications (1)
Al-Kali A, Aldoss I, Atherton PJ, Strand CA, Shah B, Webster J, Bhatnagar B, Flatten KS, Peterson KL, Schneider PA, Buhrow SA, Kong J, Reid JM, Adjei AA, Kaufmann SH. A phase 2 and pharmacological study of sapanisertib in patients with relapsed and/or refractory acute lymphoblastic leukemia. Cancer Med. 2023 Dec;12(23):21229-21239. doi: 10.1002/cam4.6701. Epub 2023 Nov 13.
PMID: 37960985DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Aref Al-Kali, M.D.
- Organization
- Mayo Clinic
Study Officials
- PRINCIPAL INVESTIGATOR
Aref Al-Kali
Mayo Clinic Cancer Center LAO
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 26, 2015
First Posted
June 29, 2015
Study Start
April 6, 2017
Primary Completion
December 28, 2018
Study Completion
March 5, 2024
Last Updated
March 3, 2025
Results First Posted
May 24, 2022
Record last verified: 2025-02