Sapanisertib for Acute Lymphoblastic Leukemia

No longer recruiting at 15 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Proton pump inhibitors

Disqualifiers: Active cancers, Uncontrolled illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks per course

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called sapanisertib for individuals with acute lymphoblastic leukemia (ALL) that has either returned after remission or did not respond to previous treatments. Sapanisertib blocks certain enzymes that cancer cells need to grow. The trial suits those with ALL who have tried other therapies without success or are newly diagnosed but cannot undergo intensive chemotherapy. Participants should have a specific percentage of cancer cells in their bone marrow and be at least four weeks past any other cancer treatments. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before starting. You must stop taking glucocorticoids, hydroxyurea, and tyrosine kinase inhibitors at least 24 hours before the trial begins. If you're on a proton pump inhibitor, you need to stop it 7 days before starting the study drugs.

Is there any evidence suggesting that sapanisertib is likely to be safe for humans?

Research shows that sapanisertib has been tested in patients with relapsed or hard-to-treat acute lymphoblastic leukemia (ALL). One study found that taking 3 mg of sapanisertib daily was safe for patients, but it wasn't very effective when used alone. Other studies have found that sapanisertib is generally safe for people with various types of cancer. While some side effects might occur, they are usually not serious. Overall, sapanisertib is well-tolerated, but monitoring for side effects remains important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for acute lymphoblastic leukemia?

Sapanisertib is unique because it targets a specific pathway involved in cell growth and survival, namely the mTOR pathway, which is often overactive in acute lymphoblastic leukemia (ALL) cells. While standard treatments for ALL typically include chemotherapy and targeted therapies like tyrosine kinase inhibitors, sapanisertib offers a novel approach by directly inhibiting this pathway, potentially leading to more effective control of the disease. Researchers are excited about sapanisertib because it may offer an innovative option for patients who don't respond well to existing treatments, providing a new avenue for managing this challenging condition.

What evidence suggests that sapanisertib might be an effective treatment for acute lymphoblastic leukemia?

Research has shown that sapanisertib, the investigational treatment in this trial, has limited success when used alone for relapsed or hard-to-treat acute lymphoblastic leukemia (ALL). Although safe for patients, it is not very effective at stopping cancer growth on its own. Lab studies have observed sapanisertib killing ALL cells, indicating some promise in early tests. However, clinical results suggest its impact as a single treatment is minimal. Therefore, while it shows potential, further research is needed to confirm its effectiveness in treating ALL. ^{1 2 3 6 7}

Who Is on the Research Team?

Aref Al-Kali

Principal Investigator

Mayo Clinic Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults with acute lymphoblastic leukemia that's come back or hasn't responded to treatment. They should have controlled blood sugar, no severe active infections, and a life expectancy over 2 months. Pregnant women can't join, and participants must use effective contraception.

Inclusion Criteria

Patients with bone marrow blasts of at least 10%

Patients with ability to understand and sign a written informed consent document

Patients with a life expectancy of > 2 months

Exclusion Criteria

I haven't had chemotherapy or radiotherapy in the last 4 weeks or still have side effects.

I am taking proton pump inhibitors during the study.

Patients with baseline prolongation of the rate-corrected QT interval (QTc) > 480 milliseconds or history of congenital long QT syndrome or Torsades de pointes

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive sapanisertib orally daily on days 1-21. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

4 weeks per course

Monthly visits for assessment

Extended Treatment

Non-responders and those in partial response at the end of course 4 may receive sapanisertib daily on days 1-28. Courses repeat every 28 days.

4 weeks per course

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Sapanisertib

Trial Overview The trial tests Sapanisertib's effectiveness on relapsed/refractory acute lymphoblastic leukemia by blocking enzymes needed for cancer cell growth. It includes lab biomarker analysis and pharmacological studies to understand how the drug works.

How Is the Trial Designed?

Group I: Treatment (sapanisertib) Experimental Treatment 3 Interventions

Patients 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.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37960985/

A phase 2 and pharmacological study of sapanisertib in ... Conclusion: In summary, single-agent sapanisertib had a good safety profile but limited target inhibition or efficacy in ALL as a single agent.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.e18506

A phase II study (NCI9775) of sapanisertib (MLN0128/TAK- ... SAP induces apoptosis of malignant lymphoid cells in vitro and in xenografts, with greatest effects in ALL cell lines. We aim to assess ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02484430?term=Sapanisertib&rank=17

Sapanisertib in Treating Patients With Relapsed and/or ... This phase II trial studies how well sapanisertib works in treating patients with acute lymphoblastic leukemia that has returned after a period of ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/abs/10.1002/cam4.6701

A phase 2 and pharmacological study of sapanisertib in ... Sapanisertib 3 mg daily was safe for patients with relapsed/refractory acute lymphoblastic leukemia. Its efficacy as single agent is ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10726920/

A phase 2 and pharmacological study of sapanisertib in ... Sapanisertib 3 mg daily was safe for patients with relapsed/refractory acute lymphoblastic leukemia. Its efficacy as single agent is limited.

6. invivochem.com invivochem.com/ink-128-mln0128.html

Sapanisertib (INK 128; MLN 0128) | mTOR1/2 inhibitor INK 128 exhibits tumor growth inhibition efficacy at a dose of 0.3 mg/kg/day in a ZR-75-1 breast cancer xenograft model. In multiplexenograft models, daily oral ...

7. nature.com nature.com/articles/s41416-020-01041-x

Phase 1 study of mTORC1/2 inhibitor sapanisertib (TAK- ... Conclusions. Sapanisertib demonstrated a manageable safety profile, with preliminary antitumour activity observed in RCC and endometrial cancer.