Oral vs IV Cladribine for Acute Myeloid Leukemia

Recruiting in Houston (>99 mi)

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

40 Participants Needed

Trial Summary

What is the purpose of this trial?

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).

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.

What data supports the effectiveness of the drug cladribine for treating acute myeloid leukemia?

Cladribine has shown promising results in treating acute myeloid leukemia (AML), with studies reporting complete response rates of about 50% in relapsed/refractory adults and 70% in newly diagnosed adults. Additionally, cladribine-containing regimens have improved complete remission rates compared to traditional treatments for newly diagnosed AML patients. ^{1 2 3 4 5}

What data supports the effectiveness of the drug cladribine for treating acute myeloid leukemia?

Research shows that cladribine, when added to standard chemotherapy, improves the complete remission rates in patients with acute myeloid leukemia. In studies, combination regimens with cladribine have shown response rates of about 50% in relapsed/refractory adults and 70% in newly diagnosed adults, indicating its potential effectiveness. ^{1 2 3 4 5}

Is cladribine safe for use in humans?

Cladribine has been studied for various conditions, including acute myeloid leukemia and hairy cell leukemia. It is generally considered safe, but like many cancer treatments, it can have side effects such as infections and fever. The studies show that while it can be effective, patients may need supportive care, such as antibiotics and blood transfusions, during treatment. ^{1 5 6 7 8}

Is cladribine safe for humans?

Cladribine has been studied for safety in various conditions, including acute myeloid leukemia and hairy cell leukemia. It has similar safety profiles to other treatments used for these conditions, but it may increase the risk of infections when added to standard treatment regimens. ^{1 5 6 7 9}

What makes the drug cladribine unique for treating acute myeloid leukemia?

Cladribine is unique because it can be administered both orally and intravenously, offering flexibility in treatment. It is an adenosine deaminase resistant analog that enhances the uptake of cytarabine, a standard chemotherapy drug, potentially improving treatment outcomes for acute myeloid leukemia. ^{1 3 5 7 10}

What makes the drug cladribine unique for treating acute myeloid leukemia?

Cladribine is unique because it can be administered both orally and intravenously, offering flexibility in treatment. It is an adenosine deaminase resistant analog that enhances the uptake of cytarabine, a standard chemotherapy drug, potentially improving treatment outcomes for acute myeloid leukemia. ^{1 3 5 7 10}

Research Team

Farhad Ravandi-Kashani

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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 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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetic study of oral and bolus intravenous 2-chlorodeoxyadenosine in patients with malignancy. [2017]

2. England 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. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

The role of cladribine in acute myeloid leukemia: an old drug up to new tricks. [2021]

4. England 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. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Revisiting the role of cladribine in acute myeloid leukemia: an improvement on past accomplishments or more old news? [2014]

6. Canada 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). [2013]

7. England pubmed.ncbi.nlm.nih.gov

Treatment of hairy cell leukemia with cladribine (2-chlorodeoxyadenosine) by subcutaneous bolus injection: a phase II study. [2020]

8. England 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. [2019]

9. China 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]. [2022]

10. Germany pubmed.ncbi.nlm.nih.gov

Clinical and toxicological aspects of the antineoplastic drug cladribine: a review. [2019]