Imetelstat + Chemotherapy for Acute Myeloid Leukemia

Recruiting at 18 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Children's Oncology Group

Must not be taking: Corticosteroids, Investigational drugs

Disqualifiers: Pregnancy, Uncontrolled infection, Seizure disorder, others

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

Compensation: Varies

Number of Visits: 1

Duration: 8 weeks

36 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments for certain blood cancers, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), that have not responded to previous treatments or have recurred. It combines imetelstat, an experimental drug that may inhibit cancer cell growth, with two chemotherapy drugs, fludarabine and cytarabine, to determine if this combination is more effective than current options. The goal is to identify the safest and most effective dose of imetelstat when used with these chemotherapy drugs. This trial may suit patients aged 1 to 18 who have experienced a return or persistence of these diseases despite treatment. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering patients the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it does mention that patients currently receiving other anti-cancer agents are not eligible, except for those on hydroxyurea, which must be stopped 24 hours before starting the trial. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that imetelstat was generally well-tolerated by patients with myelodysplastic syndrome. Some patients experienced low blood counts, fatigue, and nausea, but these effects were manageable. Research on fludarabine, a drug often used to treat leukemia, has shown it can cause low blood counts and infections, which are common and expected side effects of chemotherapy. Cytarabine, another drug for leukemia, has similar side effects, such as low blood counts and nausea.

This trial tests a combination of these drugs. The study is in its early phase, so researchers are closely monitoring the treatment's safety. Early-phase trials primarily focus on ensuring treatments are safe for people. While some information is known about each drug, the combination is still under careful study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatment involving Imetelstat for Acute Myeloid Leukemia (AML) because it targets a unique mechanism — the inhibition of telomerase. Most standard treatments for AML, like chemotherapy with cytarabine and fludarabine, focus on killing rapidly dividing cells, but Imetelstat specifically disrupts the enzyme telomerase, which is crucial for cancer cell immortality. By blocking telomerase, Imetelstat potentially limits the cancer cells' ability to multiply indefinitely, offering a novel approach that complements existing therapies. This targeted action could lead to improved outcomes for patients and represents a promising advancement in AML treatment strategies.

What evidence suggests that this trial's treatments could be effective for acute myeloid leukemia?

Research shows that imetelstat, one of the treatments in this trial, has achieved early success in treating more severe cases of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). It has also reduced the need for red blood cell transfusions in some patients. Fludarabine, another treatment option in this trial, led to complete remission in about 51% of patients with recurring or hard-to-treat acute leukemias when used in various treatment plans. Cytarabine, also part of this trial, is a key chemotherapy drug that has achieved remission in 60% to 80% of AML patients, although these remissions often do not last long. In this trial, these treatments are combined to attack cancer cells in different ways, potentially providing a stronger effect for patients with difficult-to-treat or recurring AML, MDS, and JMML. ^{1 5 6 7 8}

Who Is on the Research Team?

Alexandra M Stevens

Principal Investigator

Pediatric Early Phase Clinical Trial Network

Are You a Good Fit for This Trial?

This trial is for children and teenagers (1-18 years old) with certain types of leukemia or myelodysplastic syndrome that haven't improved after treatment or have returned. Participants must have specific levels of cancer cells in their bone marrow, confirmed by lab tests.

Inclusion Criteria

I have fully recovered from my previous cancer treatments.

I meet the specific requirements for my treatment plan.

I have a specific type of leukemia or myelodysplastic syndrome that has relapsed.

Exclusion Criteria

I am taking medication to prevent graft-versus-host disease after a transplant.

My corticosteroid dose is changing.

I am not currently taking any experimental drugs or cancer treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive imetelstat IV on days 1 and 8, fludarabine IV on days 2-6, and cytarabine IV on days 2-6 of each cycle. Treatment repeats every 28 days for up to 2 cycles.

8 weeks

Multiple visits for IV administration

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

5 years

Periodic visits for monitoring

What Are the Treatments Tested in This Trial?

Interventions

• Cytarabine
• Fludarabine
• Imetelstat

Trial Overview The trial is testing the highest safe dose of Imetelstat combined with Fludarabine and Cytarabine in young patients. It aims to find out if this combination can better treat refractory or recurrent acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and juvenile myelomonocytic leukemia (JMML).

How Is the Trial Designed?

Group I: Treatment (Imetelstat, fludarabine, cytarabine) Experimental Treatment 11 Interventions

Patients receive imetelstat IV over 2 hours on days 1 and 8, fludarabine IV over 1 hour on days 2-6, and cytarabine IV over 1-3 hours on days 2-6 of each cycle. Patients also receive cytarabine IT alone or with methotrexate IT, and hydrocortisone IT at the provider's discretion. Patients may also receive leucovorin calcium IV or PO 24 and 30 hours after each IT triples dose. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO, bone marrow biopsy and/or aspiration, blood sample collection, and lumbar puncture for CSF sample collection during screening and on the trial.

Cytarabine is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Cytosar-U for:

• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Chronic myeloid leukemia
• Meningeal leukemia

Approved in European Union as Depocyt for:

• Lymphomatous meningitis

Approved in Canada as Cytosar-U for:

• Acute myeloid leukemia
• Acute lymphocytic leukemia
• Chronic myeloid leukemia

Who Is Running the Clinical Trial?

Children's Oncology Group

Lead Sponsor

Trials

467

Recruited

241,000+

Geron Corporation

Industry Sponsor

Trials

20

Recruited

1,500+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The Mito-FLAG treatment regimen for relapsed or refractory acute myeloid leukemia (r/r AML) demonstrated a high overall response rate of 75.8%, with 56.1% of patients achieving complete remission after treatment.

Patients who successfully transitioned to allogeneic hematopoietic stem cell transplantation (alloHSCT) experienced significantly improved median overall survival of 17 months compared to just 3 months for those who did not undergo the transplant, highlighting the importance of this treatment pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome of patients with relapsed or refractory acute myeloid leukemia treated with Mito-FLAG salvage chemotherapy. Mühleck, R., Scholl, S., Hilgendorf, I., et al.[2022]

In a pilot study involving 17 patients with acute myeloid leukemia (AML), the combination of fludarabine, topotecan, and cytarabine (FTA) resulted in a 35% complete remission rate, indicating its potential efficacy in treating this condition.

However, the treatment was associated with significant side effects, as 41% of patients experienced severe diarrhea, highlighting the need for careful monitoring and further investigation of FTA's safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A fludarabine, topotecan, and cytarabine regimen is active in patients with refractory acute myelogenous leukemia. Giles, FJ., Cortes, JE., Kantarjian, HM., et al.[2013]

The combination of CLAG (cladribine, cytarabine, granulocyte colony-stimulating factor) and imatinib mesylate (IM) showed a 37% overall response rate in a phase II study involving 38 patients with relapsed or refractory acute myeloid leukemia (AML), indicating potential efficacy in this challenging patient population.

The treatment was well tolerated, with a median overall survival of 11.1 months and a median progression-free survival of 4.9 months, suggesting that this regimen could be a viable option for patients with poor-risk AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase II Study of CLAG Regimen Combined With Imatinib Mesylate for Relapsed or Refractory Acute Myeloid Leukemia. Mirza, AS., Lancet, JE., Sweet, K., et al.[2018]

In a phase III trial involving 112 newly diagnosed AML patients under 60 years, the FLAI regimen (fludarabine, cytarabine, and idarubicin) resulted in a significantly higher complete remission (CR) rate of 74% compared to 51% for the ICE regimen (idarubicin, Ara-C, and etoposide).

FLAI was associated with lower rates of both hematological and non-hematological toxicities, particularly gastrointestinal issues, making it a safer option for induction treatment in AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicentre phase III trial on fludarabine, cytarabine (Ara-C), and idarubicin versus idarubicin, Ara-C and etoposide for induction treatment of younger, newly diagnosed acute myeloid leukaemia patients. Russo, D., Malagola, M., de Vivo, A., et al.[2013]

Clofarabine combined with cytarabine (Ara-C) showed a 53% overall response rate in 30 adult patients with relapsed or refractory acute myeloid leukemia (AML), including a 47% complete remission rate, demonstrating its efficacy in both untreated and previously treated patients.

The treatment was particularly beneficial for older patients with a history of cardiovascular disease, providing a viable option for remission induction that could lead to curative hematopoietic stem cell transplantation, despite a 30-day mortality rate of 20%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Report of a phase II study of clofarabine and cytarabine in de novo and relapsed and refractory AML patients and in selected elderly patients at high risk for anthracycline toxicity. Agura, E., Cooper, B., Holmes, H., et al.[2021]

Current frontline treatments for acute myeloid leukemia (AML) using ara-C and topoisomerase II agents achieve complete response rates of 70%, but long-term survival remains low at 25%.

Newer agents like nucleoside analogs and hypomethylating agents show promise, with combination therapies yielding higher complete response rates, particularly when used alongside traditional treatments like ara-C.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New chemotherapeutic agents in acute myeloid leukemia. Kantarjian, HM., Estey, EH., Keating, MA.[2013]

In a study of 15 patients with refractory or relapsed acute myeloid leukemia (AML), high-dose cytarabine (ARA-36) achieved a complete remission rate of 60%, demonstrating significant efficacy as a salvage therapy.

Despite the promising remission rates, the one-year overall survival was only 54%, indicating that while ARA-36 is effective, the prognosis for these high-risk patients remains poor, with manageable but notable toxicities observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose cytarabine as salvage therapy for relapsed or refractory acute myeloid leukemia--is more better or more of the same? Wolach, O., Itchaki, G., Bar-Natan, M., et al.[2019]

Lenvatinib demonstrated a dose-dependent inhibition of acute myeloid leukemia (AML) cell growth in vitro, suggesting its potential as an effective treatment option.

In vivo studies showed that lenvatinib significantly restricted the growth of AML tumors in mice, indicating its efficacy in a living organism model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The multiple-kinase inhibitor lenvatinib inhibits the proliferation of acute myeloid leukemia cells. Feng, F., Li, X., Li, R., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40348597/

The Clinical Safety and Efficacy of Cytarabine ... For newly diagnosed individuals, CPX-351 led to complete remission rates of 41%-58%, surpassing the 14%-40% associated with standard chemotherapy. Additionally, ...

2. ashpublications.org ashpublications.org/ashclinicalnews/news/8741/Intermediate-Dose-of-Cytarabine-as-Effective-as

Intermediate Dose of Cytarabine as Effective as Higher Dose ... Cytarabine-based induction therapy of AML results in remission rates of 60% to 80%; however, the remissions are short-lived. Intensification ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12552264/

Clinical outcomes with high dose cytarabine and idarubicin ... High-dose cytarabine has been the frontline therapy for the consolidation treatment of acute myeloid leukemia for many years.

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e18535

Real-world outcomes of cytarabine consolidation in older ... Conclusions: Cytarabine consolidation in patients ≥60 years with AML is safe and feasible. Neurotoxicity was rare, especially at reduced dose.

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1010222

Cytarabine Dose for Acute Myeloid Leukemia More favorable results were apparent in the 88 patients with abnormalities of core-binding factor, with a complete remission rate of 91% and 5- ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12063066/

The Clinical Safety and Efficacy of Cytarabine ... This review presents strong evidence supporting CPX‐351 as a therapeutic alternative with superior efficacy and comparable safety to standard chemotherapy ...

7. go.drugbank.com go.drugbank.com/drugs/DB00987

Cytarabine: Uses, Interactions, Mechanism of Action Cytarabine is an antineoplastic anti-metabolite used in the treatment of several forms of leukemia including acute myelogenous leukemia and meningeal leukemia.

8. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT03850535

NCT03850535 | A Study Evaluating the Safety and Efficacy ... A Study Evaluating the Safety and Efficacy of Idasanutlin in Combination With Cytarabine and Daunorubicin in Patients Newly Diagnosed With Acute Myeloid ...