Cladribine + Cytarabine for AML

Overseen By Gautam Borthakur, MBBS

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Uncontrolled illness, Allergic reactions, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Part 1: Dose-ranging phase, Part 2: Efficacy phase

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for patients with acute myeloid leukemia (AML), a type of blood cancer. The first part of the study seeks to determine the safest dose of cladribine (a chemotherapy drug) that can be combined with low-dose cytarabine (another chemotherapy drug) and venetoclax. The second part evaluates whether this dose can effectively manage AML. It seeks participants with AML that has not improved with other treatments or those with a specific type of newly diagnosed AML that affects daily life. As a Phase 1/Phase 2 trial, it focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking research.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, it does allow prior therapy with certain medications like hydroxyurea and cytarabine for emergency use. It's best to discuss your specific medications with the trial team.

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

Research has shown that cladribine is generally safe for treating acute myeloid leukemia (AML). One study found that adding cladribine to another treatment led to positive outcomes, with many patients experiencing remission, a period without symptoms. This suggests it can be effective and well-tolerated.

For cytarabine, studies indicate it is safe and practical, especially for older AML patients. Side effects are manageable, and severe reactions are rare, particularly at lower doses.

Both treatments have been used before, providing some confidence in their safety. However, since this trial is in its early stages, it aims to find the safest dose combination. Safety remains a priority, and participants will be closely monitored for any issues during the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard care for acute myeloid leukemia (AML), which typically includes intensive chemotherapy regimens, the combination of Cladribine and Cytarabine offers a fresh approach. Researchers are excited about Cladribine because it is administered orally, potentially making treatment more convenient and less invasive than traditional intravenous options. Furthermore, Cladribine works by selectively targeting and depleting certain immune cells, which could enhance its effectiveness against AML. The combination with Cytarabine, a well-established chemotherapy drug, might improve outcomes by leveraging both drugs' mechanisms to tackle the cancer more effectively.

What evidence suggests that this trial's treatments could be effective for AML?

Research has shown that combining the drugs cladribine, low-dose cytarabine (LDAC), and venetoclax may effectively treat acute myeloid leukemia (AML). One study reported that 93% of patients newly diagnosed with AML experienced complete remission, meaning their symptoms disappeared. Another study found an 85% remission rate using cladribine with LDAC. These results suggest that this drug combination could help manage the disease in many patients. However, in this trial, participants will specifically receive treatment with oral cladribine. More research is needed to confirm these findings and determine the best dosage. ^{2 6 7 8 9}

Who Is on the Research Team?

Gautam Borthakur, MBBS

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with relapsed/refractory AML or newly diagnosed ts-AML after MDS treatment, AML-M5, or RAS mutations. Participants must have proper kidney, liver, and heart function and agree to use effective birth control. Excluded are those with allergies to similar drugs, uncontrolled illnesses, psychiatric conditions affecting compliance, inability to swallow pills without modification, pregnant/breastfeeding women.

Inclusion Criteria

Provision of written informed consent prior to any study related procedures

My AML cancer has returned or is not responding to treatment.

I am 18 or older with AML that developed from treated MDS.

Exclusion Criteria

History of allergic reactions attributed to compounds of similar chemical or biologic composition to any of the compounds in the study

Patients with psychiatric illness/social situations that would limit compliance with study requirements

I do not have any uncontrolled illnesses that could affect my participation.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral cladribine in combination with low dose cytarabine (LDAC) and venetoclax. Participants may be in the hospital up to the first 5 days for monitoring.

Part 1: Dose-ranging phase, Part 2: Efficacy phase

Follow-up

Participants are monitored for safety and effectiveness after treatment, including monitoring for adverse events.

Through study completion; an average of 1 year

What Are the Treatments Tested in This Trial?

Interventions

• Cladribine
• Cytarabine

Trial Overview The study aims to determine the safest high dose of oral Cladribine combined with low-dose Cytarabine and Venetoclax in two parts: first finding the highest tolerable dose (Part 1) and then assessing its effectiveness in controlling AML (Part 2).

How Is the Trial Designed?

Group I: Part 1/2 Treatment with Oral Cladribine in Patients with Acute Myeloid Leukemia Experimental Treatment 2 Interventions

Participants may be in the hospital up to the first 5 days on study to all monitoring for tumor lysis syndrome (TLS) and toxicities.

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6549775/

Efficacy and toxicity of cladribine for the treatment ... Results: A total of 10 clinical trials including 422 refractory AML patients were analyzed. The overall CR rate was 42.2% (95% CI: 31.0–54.3%).

2. nature.com nature.com/articles/s41408-024-00982-3

Efficacy and safety of cladribine, low-dose cytarabine and ... A phase II study demonstrated a composite complete remission (CRc) rate of 93% with CLAD, LDAC and venetoclax in ND AML.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07053020

A Phase 1b/2 Open-label, Dose-ranging Safety and ... The primary objective of Phase 1 is to determine safety and tolerability of oral cladribine in patients with AML and to identify a RP2D.

4. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper202620.html

56 Phase II Study of Cladribine with Low Dose Cytarabine ... The composite complete remission (CR) rate was 85% (120/141 pts), with 73% achieving CR and 12% achieving CR with incomplete blood count ...

5. link.springer.com link.springer.com/article/10.1007/s00277-025-06389-9

Efficacy and safety of cladribine, low-dose cytarabine and ... Despite recent advances, the 5-year overall survival (OS) rate for AML remains largely unsatisfactory, at approximately 30%, with survival in ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12141118/

Efficacy and safety of cladribine, low-dose cytarabine and ... Despite recent advances, the 5-year overall survival (OS) rate for AML remains largely unsatisfactory, at approximately 30%, with survival in ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0145212618300651

Acute myeloid leukemia induction with cladribine Complete remission (CR) occurred in 71%, with overall response of 79%. One-year survival overall was 59%, with 47% (27/57) among patients ≥60 years old ...

8. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/5935/501114/Outcomes-in-Patients-with-Acute-Myeloid-Leukemia

Outcomes in Patients with Acute Myeloid Leukemia Treated ... Among those with evaluable response (n=10), ORR was 50%. Two CR/CRi pts achieved undetectable MRD by flow cytometry. MRD was not tested in the ...

9. aacrjournals.org aacrjournals.org/clincancerres/article/31/8/1407/754524/Cladribine-Added-to-Idarubicin-and-Cytarabine-as

Cladribine Added to Idarubicin and Cytarabine as an ... Cladribine added to the IA regimen was safe and effective in de novo AML. ... , et al. Acute myeloid leukemia induction with cladribine: outcomes by age and ...