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B Acute Lymphoblastic LeukemiaPhase 2NCT02484430

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

A Phase 2 study testing Laboratory Biomarker Analysis, Pharmacological Study and Sapanisertib in people with B Acute Lymphoblastic Leukemia and B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1, run by National Cancer Institute (NCI) at 14 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Laboratory Biomarker Analysis, Pharmacological Study and Sapanisertib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
16 participants
Where
14 sitesUnited States
Study dates
6 Apr 2017to 5 Mar 2024
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
Show all 10Show fewer
  • 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

Trial locations and contacts

14 sites in 1 country.

14 sites in 1 country

United States14 sites

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • University of Kansas Clinical Research Center

    Fairway, Kansas, 66205

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Mayo Clinic Hospital in Arizona

    Phoenix, Arizona, 85054

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • MedStar Georgetown University Hospital

    Washington D.C., District of Columbia, 20007

Other trials in United States

About this study

Official title: A Phase 2 Study of MLN0128 (TAK-228) in Relapsed and/or Refractory Acute Lymphoblastic Leukemia (ALL)

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the complete hematologic response (CR)/complete response incomplete (CRi) rate when sapanisertib (MLN0128 [TAK-228]) is administered to adult patients with relapsed/refractory acute lymphoblastic leukemia (ALL).

SECONDARY OBJECTIVES:

  1. To determine the overall response rate (CR, CRi/partial response (PR)/morphologic leukemia free state [MLFS]).

II. To determine the CR/CRi duration when MLN0128 (TAK-228) is administered to adult patients with relapsed/refractory ALL.

III. To determine the frequency of proceeding to allogeneic stem cell transplantation (SCT) for patients with relapsed/refractory ALL who achieve a response on MLN0128 (TAK-228).

IV. To determine the overall survival for relapsed/refractory ALL patients on MLN0128 (TAK-228).

TERTIARY OBJECTIVES:

  1. To examine the pharmacokinetics of MLN0128 (TAK-228) in ALL patients. II. To assess whether phosphorylation of the mTOR substrate 4EBP1 decreases in leukemic blasts harvested from the bone marrow on day 8 compared to baseline.

III. To assess in an exploratory fashion whether MLN0128 (TAK-228) enhances expression of the pro-apoptotic proteins Bim and Puma in marrow ALL cells.

IV. To assess in an exploratory fashion whether Mcl-1 levels decrease in blast cells during MLN0128 (TAK-228) treatment.

  1. To assess in an exploratory fashion whether a) the phospho-protein pattern at baseline or b) MLN0128 (TAK-228)-associated changes in the phospho-protein pattern differs between ALL samples that respond to therapy and those that do not.

OUTLINE:

Patients receive sapanisertib orally (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.

After completion of study treatment, patients are followed up every 3 months.

Being tested
Laboratory Biomarker Analysis, Pharmacological Study, Sapanisertib
Medical subject headings
Burkitt Lymphoma, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Pharmacological StudyOther

    Correlative studies

  • SapanisertibDrug

    Also called INK-128, INK128, MLN-0128, MLN0128

    Given PO

Study groups in NCT02484430
Study groupRoleWhat they receive
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.
Receives: Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Sapanisertib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 61 days

Secondary outcomes (5)

  1. Overall Response

    ORR will be estimated by the total number of complete or partial responses (CR, CRi or PR), or morphologic leukemia free state [MLFS]) divided by the total number of evaluable patients. Exact binomial 95% confidence intervals for the true overall response rate will be calculated.

    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 Partial Response (PR) is defined as the presence of trilineage hematopoiesis in the bone marrow with recovery of ANC and platelet count to above levels, but with 5-25% bone marrow blasts and ≥50% decrease in bone marrow blast percentage from baseline.

    Measured: 61 days

  2. Duration of Complete Response

    The distribution of duration of complete response will be estimated using the method of Kaplan-Meier.

    Measured: 0 days

  3. 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

    The frequency is estimated by the number of patients who proceed to allogeneic SCT after achieving response divided by the total number of evaluable patients who achieved a response. All evaluable patients who achieved a response will be used for this analysis. Exact binomial 95% confidence intervals for the true overall response rate will be calculated.

    Measured: 0 days

  4. Overall Survival

    The distribution of survival time will be estimated using the method of Kaplan-Meier.

    Measured: 23 months

  5. Incidence of Adverse Events, Measured Per National Cancer Institute Common Terminology Criteria for Adverse Events Version 4

    The maximum grade for each type of adverse event will be recorded for each patient, and frequency tables will be reviewed to determine patterns. For this endpoint, we are reporting the maximum grade adverse event per patient.

    Measured: 91 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Jun 2015 (estimated)
  2. Study start6 Apr 2017
  3. Primary completion28 Dec 2018
  4. Study completion5 Mar 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
16 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02484430
Sponsor's protocol ID
NCI-2015-01000
Other IDs
NCI-2015-01000, MC1482, 9775, 9775, N01CM00099, UM1CA186686
Status last verified
Feb 2025
First submitted
26 Jun 2015
Last updated
3 Mar 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • 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.

    PubMed 37960985

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Laboratory Biomarker Analysis, Pharmacological Study and Sapanisertib in people with B Acute Lymphoblastic Leukemia and B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1, run by National Cancer Institute (NCI) at 14 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 26 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 May 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Complete Response (CR or CRi) (time frame: 61 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02484430, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Mar 2025.

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