Drug Combination for Pediatric Acute Leukemia

Overseen By Branko Cuglievan, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Chemotherapy, Antileukemic agents

Disqualifiers: Uncontrolled conditions, Active infections, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs to determine the best dose for children and young adults with challenging types of leukemia that have not responded to previous treatments. The focus is on a mix of four drugs: cladribine, cytarabine, decitabine (all chemotherapy drugs), and sorafenib (a targeted therapy drug). Initially, the trial will test different doses to identify the safest and most effective amount, then administer that dose to more participants. It may suit those aged 1 to 21 with certain types of leukemia that have recurred or not improved with standard treatments. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

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

The trial protocol does not specify if you must stop all current medications, but you cannot use other chemotherapeutic or anti-leukemic agents during the study, except for certain cases like intrathecal chemotherapy for CNS leukemia or hydroxyurea for rapidly proliferative disease. 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 showed that the combination of cladribine, cytarabine, decitabine, and sorafenib holds promise for treating childhood leukemia. Research indicates that this combination can be safe and tolerable for patients. Another study found that varying doses of these drugs might be manageable, with side effects similar to other treatments for children with relapsed or hard-to-treat acute leukemia. Although this trial is in the early stages, it aims to determine the optimal dose that patients can tolerate well. Safety data from other research suggests these drugs have been used successfully with manageable side effects in similar situations. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for pediatric acute leukemia because it combines cladribine, cytarabine, decitabine, and sorafenib, offering a multi-faceted approach to tackling the disease. Unlike standard treatments that may rely on single agents like methotrexate or vincristine, this combination targets leukemia cells through multiple pathways, potentially improving effectiveness. Sorafenib, a novel addition, specifically inhibits certain proteins that help cancer cells grow, which is not typically addressed by other drugs. This innovative combination could enhance treatment outcomes and offer a new hope for young patients battling this challenging condition.

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

Research shows that a combination of the drugs cladribine, cytarabine, decitabine, and sorafenib may help treat acute leukemia in children. In this trial, participants in the Phase 1 arm will receive varying doses of this combination to determine the safest and most effective dose. Previous studies have found that cladribine and cytarabine work well together for treating childhood acute myeloid leukemia. Additionally, using cladribine, cytarabine, and sorafenib together has been safe and possibly effective for young patients. These drugs aim to stop leukemia cells from growing and spreading. While more research is needed, early results are promising for improving outcomes in children with leukemia that has returned or is difficult to treat. ^{1 2 3 6 7}

Who Is on the Research Team?

Branko Cuglievan

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for children with acute leukemias that have come back or didn't respond to previous treatments. The specific types of leukemia are AML, MPAL, and ALAL. Details on who can join are not provided here.

Inclusion Criteria

My liver is functioning well, according to recent tests.

It has been over 14 days since my last cancer treatment, or 5 half-lives of the treatment.

My kidneys work well enough (creatinine clearance ≥ 30 mL/min).

Exclusion Criteria

History of or any concurrent condition, therapy, or laboratory abnormality that in the Investigator's opinion might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the participants

I currently have an infection that isn't under control.

I am not using other cancer drugs during this study, except for allowed exceptions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Participants receive cladribine, cytarabine, decitabine, and sorafenib at varying dose levels to determine safety and tolerability

8 weeks

Weekly visits for dose adjustments and monitoring

Dose Expansion

Participants receive the recommended dose level of cladribine, cytarabine, decitabine, and sorafenib found in Phase 1

8 weeks

Bi-weekly visits for monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Monthly visits

What Are the Treatments Tested in This Trial?

Interventions

• Cladribine
• Cytarabine
• Decitabine
• Sorafenib

Trial Overview The study aims to find the right dose for a drug combo (cladribine, cytarabine, decitabine, sorafenib) in young patients with certain relapsed/refractory acute leukemias.

How Is the Trial Designed?

Group I: Phase 1 Experimental Treatment 4 Interventions

Participants enrolled in Phase 1, the dose level of cladribine, cytarabine, decitabine, and sorafenib will depend on when you join this study. Up to 2 dose levels of this drug combination may be tested. Between 3-6 participants will be enrolled in each dose level. The first group of participants will receive the starting dose level of this drug combination. If no intolerable side effects are seen, the next group of participants will receive the higher dose level of this drug combination.

Group II: Dose Expansion Experimental Treatment 4 Interventions

Participants enrolled in Dose Expansion, you will receive cladribine, cytarabine, decitabine, and sorafenib at the recommended dose level found in Phase 1.

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

Approved in United States as Leustatin for:

• Hairy cell leukemia
• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin's lymphoma
• Multiple sclerosis

Approved in European Union as Litak for:

• Hairy cell leukemia
• Chronic lymphocytic leukemia (CLL)
• Non-Hodgkin's lymphoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Published Research Related to This Trial

A new low-intensity treatment regimen combining cladribine and low-dose cytarabine alternating with decitabine showed promising results in elderly or unfit patients with acute myeloid leukaemia (AML), with a median disease-free survival of 10.8 months and a median overall survival of 13.8 months based on a study of 118 patients.

The regimen was well tolerated, with only 1% of patients experiencing early death within the first 4 weeks, indicating a favorable safety profile compared to traditional therapies, which often have higher toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cladribine and low-dose cytarabine alternating with decitabine as front-line therapy for elderly patients with acute myeloid leukaemia: a phase 2 single-arm trial. Kadia, TM., Cortes, J., Ravandi, F., et al.[2019]

Cladribine (CdA) has shown significant efficacy in treating acute myeloid leukemia (AML), with complete response rates of up to 70% in newly diagnosed adults and around 50% in relapsed/refractory cases, based on various studies.

Despite its effectiveness and similar toxicity profiles to existing treatments, many medical centers have not yet adopted CdA combination regimens for managing these challenging AML populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Revisiting the role of cladribine in acute myeloid leukemia: an improvement on past accomplishments or more old news? Freyer, CW., Gupta, N., Wetzler, M., et al.[2014]

In a study involving 96 children with acute myeloid leukemia (AML), the combination of cladribine and continuous-infusion cytarabine showed promising efficacy, with 5-year event-free survival and overall survival rates of 44.1% and 50.0%, respectively.

While both treatment arms (daily vs. continuous infusion) did not show significant differences in blast percentages or Ara-CTP levels, the continuous infusion (arm B) suggested trends toward better complete remission rates and overall survival, indicating it may be a more effective approach for therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination of cladribine and cytarabine is effective for childhood acute myeloid leukemia: results of the St Jude AML97 trial. Rubnitz, JE., Crews, KR., Pounds, S., et al.[2021]

In a study of 55 children with relapsed/refractory acute myeloid leukemia (R/R-AML), the CLAG-M treatment showed an overall response rate of 80%, significantly outperforming the MEC/IEC treatment, which had a response rate of 51%.

CLAG-M also resulted in better overall survival (66.8% vs. 40.4%) and progression-free survival (52.6% vs. 34.9%) at 3 years compared to MEC/IEC, particularly benefiting low-risk patients, while those with the FLT3-ITD mutation had poorer outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved outcome of children with relapsed/refractory acute myeloid leukemia by addition of cladribine to re-induction chemotherapy. Ruan, M., Liu, LP., Zhang, AL., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06474663

NCT06474663 | A Phase I Study Investigating the ... Participants enrolled in Dose Expansion, you will receive cladribine, cytarabine, decitabine, and sorafenib at the recommended dose level found in Phase 1.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7897947/

Improved outcome of children with relapsed/refractory ... The combination of cladribine/Ara‐C/granulocyte‐colony stimulating factor and mitoxantrone (CLAG‐M) shown promising results in adult R/R‐AML. We ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-05386

Cladribine, Cytarabine and Sorafenib Alternating with ... Giving cladribine, cytarabine and sorafenib alternating with decitabine and sorafenib may be safe, tolerable, and/or effective in treating pediatric patients ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11592422/

Cladribine-Based Therapy for Acute Myeloid Leukemia in ... Combination of cladribine and cytarabine is effective for childhood acute myeloid leukemia: Results of the St Jude AML97 trial. Leukemia.

5. researchgate.net researchgate.net/publication/327006037_Cladribine_and_low-dose_cytarabine_alternating_with_decitabine_as_front-line_therapy_for_elderly_patients_with_acute_myeloid_leukaemia_a_phase_2_single-arm_trial

Cladribine and low-dose cytarabine alternating with ... We studied a new low-intensity regimen of cladribine combined with low-dose cytarabine alternating with decitabine, aimed at improving outcomes in this ...

6. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/cam4.3681

Improved outcome of children with relapsed/refractory ... CLAG-M regimen is a more valid option with similar adverse events as a salvage treatment for R/R-AML in children when compared with ...

7. ashpublications.org ashpublications.org/blood/article/143/1/11/498663/How-I-treat-refractory-and-relapsed-acute-myeloid

How I treat refractory and relapsed acute myeloid leukemia Using a series of 3 illustrative cases, Thol and colleagues discuss their approach to relapsed/refractory acute myeloid leukemia.