Oral vs IV Cladribine for Acute Myeloid Leukemia

Overseen By Farhad Ravandi-Kashani, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Live vaccines

Disqualifiers: Uncontrolled illness, Hepatitis, HIV, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 5 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a potential new treatment for acute myeloid leukemia (AML) using an oral form of the drug cladribine, compared to the traditional intravenous (IV) method. The goal is to determine if the oral administration is as safe and effective as the IV method. Participants will receive either a combination of oral and IV doses or only the oral form, depending on their assigned group. This trial may suit individuals diagnosed with hairy cell leukemia (HCL) or those previously treated for T-cell prolymphocytic leukemia who are candidates for cladribine therapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new form of therapy.

Do I need to stop my current medications to join the 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.

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

The trial information does not specify if 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 has shown that cladribine, whether taken as a pill or through an IV, has been studied for its safety in people with acute myeloid leukemia (AML). Studies of cladribine administered by IV found it was generally well-tolerated. In a study with children, no new safety issues emerged, although four cases of the disease worsening led to deaths within 30 days.

For cladribine taken as a pill, research is ongoing to confirm its safety. Current studies aim to find the right dose that balances safety and effectiveness. Oral cladribine remains in the early stages of testing, so researchers are closely monitoring it for any side effects.

Both forms of cladribine are under careful study, and potential participants should know that ensuring the treatment's safety is a top priority in these trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for acute myeloid leukemia that often involve intravenous chemotherapy, cladribine offers a potentially more convenient oral dosing option. Researchers are excited about cladribine because it could simplify treatment regimens by allowing patients to take the medication orally, which is less invasive and could improve adherence to therapy. This trial is exploring both a combination of oral and IV cladribine and an all-oral regimen, which could be groundbreaking for patient comfort and accessibility.

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

Research has shown that cladribine may help treat acute myeloid leukemia (AML). In past studies, patients who took cladribine with other medications often went into remission, meaning their cancer symptoms disappeared. For example, one study found that 85% of patients who took cladribine with low-dose cytarabine went into complete remission. Another study showed a 42.2% remission rate in patients whose AML was hard to treat. While these studies mainly examined the drug given through an IV, this trial will test both oral and IV forms of cladribine to determine if the pill form works as well. Overall, cladribine has shown promise in helping patients with AML achieve remission. ^{1 2 3 4 6}

Who Is on the Research Team?

Farhad Ravandi-Kashani

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults aged ≥18 with Acute Myeloid Leukemia, Myelodysplastic Syndrome, or certain types of leukemia. Must have good kidney and liver function, not be HIV positive or have uncontrolled illnesses. Women must use birth control if of childbearing potential; men must also agree to contraception.

Inclusion Criteria

My kidney and liver tests are within normal ranges.

I am not pregnant, not breastfeeding, and agree to use 2 forms of birth control if of childbearing age.

I am a male willing to use contraception during and for 3 months after the study.

Exclusion Criteria

You have had allergic reactions to similar medicines or substances that are similar to the ones being used in the study.

I do not have an active hepatitis infection or positive test results for hepatitis B or C.

My heart's electrical cycle is within a normal range.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral cladribine followed by intravenous cladribine for pharmacokinetic comparison

5 days

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Cladribine

Trial Overview The study is testing an oral form of the drug Cladribine against the standard IV form for effectiveness in treating specific blood cancers. Participants will receive both forms at different times to compare how their bodies absorb them.

How Is the Trial Designed?

Group I: Cohort 3 (All-Oral HCL) Experimental Treatment 1 Intervention

Participants will all receive the same dose of oral cladribine over the course of 5 days.

Group II: Cohort 2 (PK) Experimental Treatment 1 Intervention

Participants will only receive 1 dose of oral cladribine, followed by 4 daily doses of cladribine by vein

Group III: Cohort 1 (Pilot) Experimental Treatment 1 Intervention

Participants will only receive 1 dose of oral cladribine, followed by 4 daily doses of cladribine by vein

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 study found that the absolute bioavailability of oral 2-chlorodeoxyadenosine (cladribine) is approximately 37%, indicating that a significant portion of the drug is absorbed when taken orally by patients with advanced malignancies.

Both oral and intravenous administrations of 2-CdA showed similar pharmacokinetic profiles with no significant accumulation of the drug, and the main side effect observed was neutropenia, highlighting the drug's predictable absorption and safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic study of oral and bolus intravenous 2-chlorodeoxyadenosine in patients with malignancy. Saven, A., Cheung, WK., Smith, I., 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]

The addition of cladribine (CdA) to standard chemotherapy regimens for acute myeloid leukemia (AML) has shown promising response rates, with about 50% in relapsed/refractory cases and around 70% in newly diagnosed AML patients.

Recent studies indicate that a low-intensity combination of CdA and cytarabine (ARA-C), alternating with decitabine, may be particularly effective for older patients with AML, suggesting a potential new treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of cladribine in acute myeloid leukemia: an old drug up to new tricks. Molica, M., Breccia, M., Capria, S., et al.[2021]

In a study of 62 patients with hairy cell leukemia, a single course of 2-chlorodeoxyadenosine (CDA) administered via subcutaneous injections resulted in a high overall response rate of 97%, with 76% achieving complete remission and 21% partial remission.

The subcutaneous method of administration is not only more convenient for patients but also has a similar safety profile to intravenous infusion, with leukopenia being the main side effect, though no significant opportunistic infections were reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of hairy cell leukemia with cladribine (2-chlorodeoxyadenosine) by subcutaneous bolus injection: a phase II study. von Rohr, A., Schmitz, SF., Tichelli, A., et al.[2020]

Cladribine is a well-tolerated antineoplastic drug that shows significant efficacy in treating hairy cell leukemia and chronic lymphocytic leukemia, with response rates ranging from 37% to 100% in various studies involving different types of blood cancers.

The drug primarily causes myelosuppression as a dose-limiting toxicity, while non-hematological side effects are generally mild or absent, suggesting a favorable safety profile for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and toxicological aspects of the antineoplastic drug cladribine: a review. Guchelaar, HJ., Richel, DJ., Schaafsma, MR.[2019]

In a study of 309 newly diagnosed acute myeloid leukemia (AML) patients, adding cladribine to the standard treatment of daunorubicin and cytarabine did not significantly change the overall incidence of infectious complications during induction therapy.

While there was a trend towards fewer bacteremias in the cladribine group, the difference was not statistically significant, and both treatment groups had similar recovery rates from infections, indicating that cladribine does not increase infection risk in AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infectious complications in patients with acute myeloid leukemia treated according to the protocol with daunorubicin and cytarabine with or without addition of cladribine. A multicenter study by the Polish Adult Leukemia Group (PALG). Lech-Maranda, E., Seweryn, M., Giebel, S., et al.[2013]

In a phase II trial involving 63 patients aged over 60 with acute myeloid leukaemia (AML), the addition of intermittent cladribine to intermediate-dose cytosine arabinoside and idarubicin resulted in a higher complete remission rate of 62%, compared to 35% for the two-drug therapy alone.

The treatment was well-tolerated with limited toxicity, and the median survival was 14 months, indicating that this combination therapy could be a promising option for older AML patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased remissions from one course for intermediate-dose cytosine arabinoside and idarubicin in elderly acute myeloid leukaemia when combined with cladribine. A randomized population-based phase II study. Juliusson, G., Höglund, M., Karlsson, K., et al.[2019]

In a Phase 2 clinical trial involving 109 pediatric patients with acute myeloid leukemia (AML) at first relapse, the combination of 2-chlorodeoxyadenosine (2-CDA) and idarubicin showed a 51% overall response rate, with a 46% complete response rate, indicating its potential effectiveness in treating this population.

The treatment had an acceptable safety profile, with significant toxicities including neutropenia (59%) and thrombocytopenia (68%), but no serious cardiac events, suggesting it could be a viable option for frontline therapy in children with AML.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of 2-chlorodeoxyadenosine plus idarubicin for children with acute myeloid leukaemia in first relapse: a paediatric oncology group study. Chaleff, S., Hurwitz, CA., Chang, M., et al.[2021]

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]

The cladribine-based intensified conditioning regimen combined with busulfan and cyclophosphamide showed promising efficacy in high-risk acute myeloid leukemia (AML) patients, achieving a 1-year overall survival rate of 78.8% and a progression-free survival rate of 79.8%.

The regimen demonstrated good safety, with only 39.3% of patients experiencing mild regimen-related toxicity and no severe toxicities (grade III/IV), making it a viable option for non-relapsed high-risk AML patients, although those with pre-transplant relapse had poorer outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy and Safety of Cladribine-based Intensified Conditioning Regimen in Hematopoietic Stem Cell Transplantation in Patients with High-Risk Acute Myeloid Leukemia]. Pan, WY., Li, KX., Wu, HY., et al.[2022]

Citations

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

Efficacy and safety of cladribine, low-dose cytarabine and ... The efficacy of the venetoclax-based regimen in R/R AML was not satisfactory, with a remission rate of 21% and a median survival of 3.0 months ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06021600

Study Details | NCT06021600 | A Phase 1, Open-Label, ... Study Overview. To compare an investigational oral form of the drug cladribine to the FDA approved form of the drug when it is given by vein (IV).

3. cancertherapyadvisor.com cancertherapyadvisor.com/news/cladribine-induction-aml/

Cladribine Improves Upon 7+3 Induction in AML The researchers found that cladribine improved the complete response (CR) rate but did not improve measurable residual disease (MRD) negativity.

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

Cladribine-Based Therapy for Acute Myeloid Leukemia in ... The 5-year event-free survival rates for childhood acute myeloid leukemia (AML) range between 49% and 64% [1,2], with relapse occurring in up to ...

5. 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.

6. 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. Patients with adverse risk or those between 45 and 60 years of age might benefit ...