Cladribine + LDAC + Decitabine for Acute Myeloid Leukemia and Myelodysplastic Syndrome

Overseen By Tapan Kadia, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Disqualifiers: Pregnancy, Uncontrolled illness, Hypersensitivity, 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

160 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a combination of three drugs—cladribine (Leustatin), low-dose cytarabine, and decitabine—can help manage acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The study will also assess the safety of these drugs when used together. Individuals with untreated AML or MDS, those who have had certain past treatments, or those whose condition has returned after treatment, may be suitable for this trial. Participants will receive the drug combination at MD Anderson. As a Phase 2 trial, the 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 information does not specify whether you need to stop taking your current medications. However, prior therapy with certain drugs like hydroxyurea and decitabine is allowed, so 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?

Research shows that combining cladribine, low-dose cytarabine, and decitabine is generally safe. Studies have found that patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) tolerate this treatment well.

Cladribine has FDA approval for treating hairy cell leukemia, indicating a reliable safety record. Cytarabine is also FDA-approved for AML patients. Decitabine is approved for MDS and remains under investigation for AML use.

Clinical trials have demonstrated that this combination can effectively control the disease and remains manageable for patients. While side effects can occur with most treatments, this combination is considered a safe option, especially for those unresponsive to other therapies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Cladribine, Cytarabine, and Decitabine for treating Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome because it offers a unique approach compared to standard treatments like chemotherapy with Cytarabine and anthracyclines. Unlike traditional chemotherapy, this treatment alternates between using Cladribine with Cytarabine and Decitabine, potentially enhancing effectiveness and reducing resistance. This regimen also leverages Decitabine's ability to modify gene expression, which might improve patient outcomes by targeting cancer cells in a novel way. By combining these agents, the treatment aims to attack leukemia cells more comprehensively and may offer hope for patients who have limited options with existing therapies.

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

This trial will evaluate a combination of three drugs—cladribine, low-dose cytarabine, and decitabine—as a potential treatment for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). Research has shown that this combination could be promising, with studies indicating it is safe and effective in controlling these diseases. Participants in this trial will receive cladribine and cytarabine, which enter the DNA of cancer cells to stop their growth, alternating with decitabine, which damages the DNA and can lead to cancer cell death. Previous studies have demonstrated strong results in managing these conditions with this combination. While cladribine is already approved for treating another type of leukemia, its use in AML remains under study. ^{1 2 3 4 6}

Who Is on the Research Team?

Tapan Kadia, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults aged 18 or older with untreated AML or high-risk MDS, who are not suitable for standard therapy. Participants must understand the study and consent to it, have adequate organ function, and agree to use contraception. Pregnant women, those with uncontrolled illnesses or hypersensitivity to the drugs used in this trial cannot participate.

Inclusion Criteria

I have AML or high-risk MDS without prior treatment.

I have previously been treated with specific medications like hydroxyurea or azacytidine.

I have AML that evolved from MDS and haven't had AML treatment before.

Exclusion Criteria

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

Patient with documented hypersensitivity to any of the components of the chemotherapy program.

Pregnant women are excluded from this study because the agents used in this study have the potential for teratogenic or abortifacient effects. Breastfeeding should also be avoided.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive cladribine by vein and cytarabine by injection for up to 2 cycles

4-8 weeks

Daily visits for drug administration

Consolidation

Participants receive alternating cycles of cladribine with cytarabine and decitabine

Up to 68 weeks

Regular visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 6-12 months

Phone calls for follow-up

What Are the Treatments Tested in This Trial?

Interventions

• Cladribine
• Cytarabine
• Decitabine

Trial Overview The study tests a combination of Cladribine, Cytarabine (LDAC), and Decitabine on patients with AML or MDS. It aims to see if these drugs can control the disease by interfering with cancer cells' DNA processing and repair mechanisms. Up to 160 participants will be enrolled at MD Anderson.

How Is the Trial Designed?

Group I: Cladribine + Cytarabine Alt. with Decitabine Experimental Treatment 3 Interventions

Induction cycle: Cladribine intravenous (IV) over approximately 1 to 2 hours, daily on days 1-5 combined with Cytarabine subcutaneous (SQ) twice daily on days 1-10. Cytarabine should be administered approximately 3-6 hours following the start of the cladribine infusion. Consolidation cycle: Cladribine IV over 1 to 2 hours, daily on days 1-3 combined with Cytarabine SQ twice daily on days 1-10. Cytarabine should be administered 3-6 hours following the start of the cladribine infusion. Alternating with: Decitabine IV over 1 to 2 hours, daily on days 1-5.

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

The combination of decitabine and idarubicin showed a synergistic effect in inducing cell death in various myeloid leukemia cell lines and primary AML cells, suggesting a more effective treatment strategy than decitabine alone.

This combination therapy not only inhibited tumor growth more effectively in mouse models but also triggered apoptosis and downregulated the Wnt/β-catenin pathway, which is linked to leukemia progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sequential combination of decitabine and idarubicin synergistically enhances anti-leukemia effect followed by demethylating Wnt pathway inhibitor promoters and downregulating Wnt pathway nuclear target. Li, K., Hu, C., Mei, C., et al.[2021]

A novel low-intensity treatment regimen of low-dose cytarabine and cladribine (LD-AC+cladribine) showed a 54% response rate in elderly patients (≥60 years) with acute myeloid leukemia (AML) who were not eligible for intensive chemotherapy, indicating its efficacy as a first-line treatment.

The median overall survival was 21 months for patients achieving complete remission and 8.8 months for those with partial remission, suggesting that while the treatment is beneficial, factors like advanced age and adverse cytogenetics negatively impact survival outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cladribine Combined with Low-Dose Cytarabine as Frontline Treatment for Unfit Elderly Acute Myeloid Leukemia Patients: Results from a Prospective Multicenter Study of Polish Adult Leukemia Group (PALG). Budziszewska, BK., Salomon-Perzyński, A., Pruszczyk, K., et al.[2021]

The modified low-dose cytarabine (mLDAC) regimen showed a significantly higher complete response rate (46.8%) in elderly acute myeloid leukemia (eAML) patients compared to decitabine (DAC) (19.0%), indicating improved efficacy in this population.

While mLDAC was associated with more frequent side effects like mucositis and neutropenic fever, the overall survival rates were similar between mLDAC and DAC groups (8.7 vs. 8.3 months), suggesting that mLDAC can be a viable alternative to DAC with comparable outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the modified low-dose cytarabine and etoposide with decitabine therapy for elderly acute myeloid leukemia patients unfit for intensive chemotherapy. Shin, SH., Cho, BS., Park, SS., et al.[2019]

In a long-term study of 68 adult patients with mastocytosis treated with cladribine (2-CdA), the overall response rate was 72%, with particularly high efficacy in indolent mastocytosis (92% response rate).

While 2-CdA showed significant clinical improvement in symptoms and reduced serum tryptase levels, it also had notable toxicities, including high rates of lymphopenia (82%) and neutropenia (47%).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term efficacy and safety of cladribine (2-CdA) in adult patients with mastocytosis. Barete, S., Lortholary, O., Damaj, G., et al.[2021]

The DAC-7 regimen, which includes cladribine, resulted in a significantly higher complete response (CR) rate of 64% after one induction cycle compared to 47% for the DA-7 regimen, indicating enhanced efficacy in treating acute myeloid leukemia.

Patients receiving DAC-7 experienced a median hospitalization time that was 7 days shorter than those on DA-7 (33 vs 40 days), and while the overall 3-year leukemia-free survival rates were similar, there was a trend suggesting improved survival for patients over 40 years old on the DAC-7 regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia. Multicenter, phase III study. Holowiecki, J., Grosicki, S., Robak, T., et al.[2013]

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]

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]

The CLAG regimen, which includes cladribine, cytarabine, and G-CSF, demonstrated significant anti-leukemic activity in refractory acute myeloid leukemia (AML), achieving a complete remission (CR) rate of 50% in a study of 58 patients.

Hematologic toxicity was the most common side effect observed, but the regimen was considered to have an acceptable safety profile, with a 1-year overall survival rate of 42% for all patients and 65% for those who achieved CR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multicenter, open, non-comparative, phase II study of the combination of cladribine (2-chlorodeoxyadenosine), cytarabine, and G-CSF as induction therapy in refractory acute myeloid leukemia - a report of the Polish Adult Leukemia Group (PALG). Wrzesień-Kuś, A., Robak, T., Lech-Marańda, E., et al.[2019]

In a study of 406 older patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS), clofarabine significantly increased complete remission rates compared to low-dose Ara-C (22% vs 12%), indicating its potential efficacy in this population.

Despite the higher remission rates with clofarabine, there was no overall survival benefit, highlighting the need for better treatment options for older patients with AML who are not fit for intensive chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clofarabine doubles the response rate in older patients with acute myeloid leukemia but does not improve survival. Burnett, AK., Russell, NH., Hunter, AE., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT01515527

NCT01515527 | Cladribine Plus Low Dose Cytarabine ... The goal of this clinical research study is to learn if cladribine given in combination with low-dose cytarabine (LDAC) and decitabine can help control the ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30115541/

Cladribine and low-dose cytarabine alternating with ... - PubMed The combination of cladribine and low-dose cytarabine alternating with decitabine appears to be a safe and highly effective regimen for the treatment of ...

3. ashpublications.org ashpublications.org/blood/article/134/Supplement_1/1360/427382/High-Activity-of-Cladribine-2-CdA-Combined-with

High Activity of Cladribine (2-CdA) Combined with Low-Dose ... Interestingly, recent studies have demonstrated clinical efficacy of cladribine combined with cytarabine in newly diagnosed AML patients. In ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2352302618301327

Cladribine and low-dose cytarabine alternating with ... The combination of cladribine and low-dose cytarabine alternating with decitabine appears to be a safe and highly effective regimen for the treatment of ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01515527?term=AREA%5BConditionSearch%5D(Congenital%20dyserythropoietic%20anemia%20OR%20%22anemia,%20congenital%20dyserythropoietic%22%20OR%20%22%20CDA%22%20OR%20%22%20congenital%20dyshaematopoietic%20anaemia%22%20OR%20%22%20congenital%20dyshaematopoietic%20anemia%22)%20AND%20AREA%5BOverallStatus%5D(NOT_YET_RECRUITING%20OR%20RECRUITING)&rank=3

Cladribine Plus Low Dose Cytarabine (LDAC) Alternating With ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

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

Efficacy and safety of cladribine, low-dose cytarabine and ... The 3-year overall survival for patients with primary refractory or relapsed acute myeloid leukemia (R/R AML) is only approximately 10% [1].