Cladribine Chemotherapy for Acute Myeloid Leukemia

Overseen By Medical College of Wisconsin Clinical Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Medical College of Wisconsin

Disqualifiers: Acute promyelocytic leukemia, active infection, pregnancy, 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: 4-10 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment plan using cladribine and mitoxantrone, both chemotherapy drugs, for individuals with acute myeloid leukemia (AML), a type of blood cancer. The trial aims to evaluate the effectiveness of these treatments for patients whose cancer has returned or is unresponsive to previous treatments. Participants may receive one of two different treatment cycles, each lasting 30 days, with a possible second cycle if needed. Eligible participants include those with AML, particularly if they have experienced a relapse or if their condition began as a related blood disorder and progressed to AML. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research shows that treatments containing cladribine are effective and safe for patients with acute myeloid leukemia (AML). Studies have shown promising results, with many patients responding well to the treatment. Cladribine's side effects are generally manageable with proper care.

Mitoxantrone, another drug in this trial, has also been studied for its safety and effectiveness in treating AML. Research indicates that treatments with mitoxantrone have manageable side effects, mostly related to blood cell counts, which doctors can monitor and treat.

Overall, both cladribine and mitoxantrone have been studied in people with similar conditions, and the safety data suggest they are generally well-tolerated. However, as with any treatment, individual experiences may vary, so discussing any concerns with a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments using cladribine and mitoxantrone for acute myeloid leukemia because they offer unique approaches compared to existing options. Unlike standard treatments that typically focus on chemotherapy drugs like cytarabine and anthracyclines, the CLLDAC and CLAG-M regimens incorporate cladribine, which can enhance the effectiveness of other chemotherapy agents by interfering with DNA synthesis and repair in cancer cells. Additionally, the option for outpatient treatment in the CLLDAC arm provides more flexibility and potentially less disruption to patients' lives. These features make these investigational regimens promising, as they might improve patient outcomes with potentially fewer side effects.

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

Research has shown that cladribine, which participants in this trial may receive as part of the CLLDAC regimen, may help treat acute myeloid leukemia (AML). In earlier studies, up to 71% of patients achieved complete remission, with no signs of the disease after treatment. Another study found a 42.2% remission rate in patients who did not respond to other treatments. Similarly, mitoxantrone, included in the CLAG-M regimen in this trial, has effectively treated AML and often outperforms some traditional drugs. These findings suggest that both cladribine and mitoxantrone could be effective options for treating AML. ^{1 2 3 6 7}

Who Is on the Research Team?

Ehab L. Atallah

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

Adults (18+) with high-risk Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML), including those who've failed hypomethylating agents, can join. They must have an ECOG score of 0-3 and meet specific health criteria like organ function tests. Pregnant women, breastfeeding mothers, and those with uncontrolled infections or Acute Promyelocytic Leukemia are excluded.

Inclusion Criteria

I can care for myself but may not be able to do heavy physical work.

I am using or willing to use effective birth control during the study.

Ability to understand a written informed consent document and the willingness to sign it

Exclusion Criteria

Pregnant or breast feeding women

I have an infection that isn't responding well to treatment.

I have been diagnosed with Acute Promyelocytic Leukemia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a cladribine-based salvage chemotherapy regimen, with each cycle lasting 30 days. A second cycle may be administered if necessary.

4-10 weeks

Outpatient visits as needed

Follow-up

Participants are monitored for safety, MRD negativity, and overall survival after treatment

4 years

What Are the Treatments Tested in This Trial?

Interventions

• Cladribine
• Mitoxantrone

Trial Overview The trial is testing two chemotherapy regimens for AML/MDS: CLAG-M (Cladribine, Cytarabine, Mitoxantrone, G-CSF) and CLLDAC (Cladribine and Cytarabine). It's a phase II study to see how well these treatments work and to understand the genetic factors that affect response to therapy.

How Is the Trial Designed?

Group I: CLLDAC regimen Experimental Treatment 1 Intervention

Subject's treatment cycle is 30 days. Subject may be treated on an outpatient basis (CLLDAC arm only). In addition, subjects who fail to achieve a CR/CRi after the first 30-day cycle may receive a second cycle of CLLDAC, per the discretion of the treating physician. Subjects who receive this second cycle should begin cycle 2 no later than 49 days after cycle 1.

Group II: CLAG-M regimen Experimental Treatment 1 Intervention

Subject's treatment cycle is 30 days.

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?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

The pilot study involving 16 patients with hematological malignancies demonstrated that a novel reduced-intensity stem cell transplantation (RIST) regimen using cladribine (2-CdA) was well tolerated, with only one patient experiencing severe regimen-related toxicities.

The RIST regimen achieved early complete donor chimerism in 14 patients and showed promising survival rates, with a 1-year overall survival rate of 69% and a disease-free survival rate of 50%, indicating potential efficacy in treating advanced leukemia and lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic potential of a reduced-intensity preparative regimen for allogeneic transplantation with cladribine, busulfan, and antithymocyte globulin against advanced/refractory acute leukemia/lymphoma. Saito, T., Kanda, Y., Kami, M., et al.[2013]

Mitoxantrone significantly improved the complete remission (CR) rate and disease-free survival (DFS) in patients with acute myeloid leukemia (AML) compared to daunorubicin, based on a review of 12 randomized controlled trials involving 4583 patients.

There was no significant difference in death during induction therapy or overall survival (OS) between mitoxantrone and daunorubicin, suggesting that while mitoxantrone may enhance remission rates, it does not increase the risk of mortality during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Dose Ratio on Mitoxantrone and Daunorubicin in Acute Myeloid Leukemia: A Systematic Review and Meta-analysis of Randomized Controlled Trials. Deng, L., Zhang, C., Ying, S., et al.[2021]

The VALOR study, involving 711 patients, showed that the combination of vosaroxin and cytarabine resulted in better complete remission rates and survival for older patients (≥60 years) with relapsed/refractory acute myeloid leukemia (AML) compared to placebo/cytarabine.

Vosaroxin demonstrated a safety profile similar to existing AML treatments, making it a promising option for older patients who often face poor outcomes due to comorbidities and unfavorable cytogenetics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vosaroxin in relapsed/refractory acute myeloid leukemia: efficacy and safety in the context of the current treatment landscape. Sedov, V., Stuart, RK.[2020]

In a phase II clinical study involving 12 adult patients with chronic myeloid leukemia in blastic phase, the combination of cladribine and mitoxantrone resulted in only 17% of patients achieving a partial response, indicating limited efficacy for this treatment regimen.

The treatment was associated with significant toxicity, including severe myelosuppression, with 33.3% of patients experiencing grade 3 or 4 neutropenia and thrombocytopenia, leading to infections and two deaths from sepsis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cladribine combined with mitoxantrone in the treatment of blastic phase of chronic myeloid leukemia. Robak, T., Góra-Tybor, J.[2013]

Cladribine (2-CdA) is an effective treatment for indolent lymphoid malignancies, such as hairy cell leukemia and indolent B-cell lymphoma, due to its ability to induce DNA strand breaks and cell death in lymphocytes, regardless of cell division.

The drug has been extensively studied and was approved by the FDA in 1993 and in Japan in 2002, demonstrating its established efficacy and clinical usefulness based on data from multiple clinical trials across the United States, Europe, and Japan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cladribine]. Ogura, M.[2013]

The combination of cladribine (2-CdA) and mitoxantrone was found to be safe and feasible for treating patients with alkylator-failed indolent lymphoma, with a maximum-tolerated dose established for further studies.

The treatment showed a high overall response rate of 70%, including 22% complete responses and 48% partial responses, indicating significant efficacy in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cladribine and mitoxantrone dose escalation in indolent non-Hodgkin's lymphoma. Saven, A., Lee, T., Kosty, M., et al.[2017]

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 of 24 patients with acute leukemia or blast crisis of chronic myelocytic leukemia, mitoxantrone treatment led to complete remission in 5 out of 20 evaluable patients, indicating its potential efficacy in this challenging patient population.

While mitoxantrone caused moderate to severe side effects like bone marrow suppression and mucositis, it did not result in cardiotoxicity, suggesting a relatively safe profile for further investigation in combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mitoxantrone in the treatment of relapsed and refractory acute leukemia. Meyer, P., Ho, AD., Ehninger, G., et al.[2019]

Cladribine-containing regimens significantly improve the complete remission rate in newly diagnosed acute myeloid leukemia (AML) patients, with a pooled complete remission rate of 64% based on 14 clinical trials involving 1058 patients.

The safety profile of cladribine is comparable to standard treatments, with no significant increase in early death rates, suggesting it is a safe option for induction treatment in AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of cladribine addition to induction treatment of newly diagnosed acute myeloid leukemia: a systematic review and meta-analysis. Pan, Q., Li, J.[2022]

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 phase II trial involving 20 patients with relapsed acute myeloid leukemia (AML), the combination of cladribine, cytarabine, and idarubicin achieved a complete remission rate of 60%, demonstrating its efficacy in this challenging condition.

The treatment was associated with significant toxicity, primarily infections, but when combined with allogeneic stem cell transplantation, it led to a 5-year survival rate of 55% among those who underwent the transplant, indicating potential for long-term survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term follow-up of Cladribine, high-dose Cytarabine, and Idarubicin as salvage treatment for relapsed acute myeloid leukemia and literature review. Mayer, K., Hahn-Ast, C., Schwab, K., et al.[2021]

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. 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 ...

3. tandfonline.com tandfonline.com/doi/full/10.1080/16078454.2021.1962047

Full article: Efficacy and safety of cladribine addition to ... The conclusion was that 58% of AML patients achieved CR after one course of treatment[Citation4]. Based on this, PALG published the results of a ...

4. 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.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/9486920/

2-Chlorodeoxyadenosine with or without daunorubicin in ... Antileukemic activity was observed in all the patients, but no single complete remission was achieved. One patient had a long-lasting partial response (response ...

6. ashpublications.org ashpublications.org/blood/article/126/8/1009/34736/Long-term-efficacy-and-safety-of-cladribine-2-CdA

Long-term efficacy and safety of cladribine (2-CdA) in adult ... The overall survival rate was 48.5% (95% CI, 30.2-77.9) at the end of follow-up because 21 patients died (31%). Median survival time was 8.2 years.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03181815

Cladribine in Combination With CAG in Patients ... The vast majority of patients with AML will die of the disease, and no standard chemotherapy regimen were defined for patients with relapsed/refractory AML.