Combining cladribine, low-dose cytarabine, and decitabine for treating acute myeloid leukemia and high-risk myelodysplastic syndrome

Phase II Study of Cladribine Plus Low Dose Cytarabine (LDAC) Induction Followed By Consolidation With Cladribine Plus LDAC Alternating With Decitabine in Patients With Untreated Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS)

This study is testing a new combination of three drugs to see if it can help people with acute myeloid leukemia or high-risk myelodysplastic syndrome feel better and manage their disease.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 160 (estimated)
• Ages: 60 Years and up
• Sex: All
• Sponsor: M.D. Anderson Cancer Center (Academic / other)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Houston, Texas)
• Trial ID: NCT01515527 on ClinicalTrials.gov

What this trial studies

This clinical research focuses on evaluating the effectiveness of a combination therapy involving cladribine, low-dose cytarabine (LDAC), and decitabine in patients diagnosed with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). Participants will undergo a treatment regimen consisting of induction and consolidation cycles, where cladribine and cytarabine are administered intravenously and via self-injection, respectively, followed by decitabine in alternating cycles. The study aims to assess both the safety and efficacy of this investigational drug combination in controlling the disease.

Who should consider this trial

Good fit: Ideal candidates for this study are patients aged 60 years and older with previously untreated AML or high-risk MDS.

Not a fit: Patients with low-risk MDS or those who have received prior extensive treatment for AML may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new effective option for patients with AML or high-risk MDS, potentially improving their disease control and outcomes.

How similar studies have performed: While the combination of these drugs is investigational for AML, similar approaches have shown promise in other studies, indicating potential for success.

Eligibility criteria

Cohort 1

Inclusion Criteria:

1. Patients with previously untreated AML or high risk MDS (\>/= 10 % blasts or IPSS \>/= intermediate-2). Prior therapy with hydroxyurea, hematopoietic growth factors, azacytidine, ATRA, or total dose of cytarabine up to 2g is allowed. Patients with history of MDS transformed to AML are eligible regardless of their prior therapy for MDS provided this will be their first induction therapy for AML.
2. Age \>/= 60 years. Patients aged \< 60 years who are unsuitable for standard induction therapy may be eligible after discussion with PI
3. Adequate organ function as defined below:

   * liver function (bilirubin \< 2mg/dL, AST and/or ALT \<3 x ULN)
   * kidney function (creatinine \< 1.5 x ULN ).
4. ECOG performance status of ≤ 2.
5. A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
6. Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient is required prior to their enrollment on the protocol.
7. Prior therapy with decitabine will be allowed unless the patient experienced progression to AML while being treated with decitabine.

Exclusion Criteria:

1. Pregnant women are excluded from this study because the agents used in this study have the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding should also be avoided.
2. Uncontrolled intercurrent illness including, but not limited to ongoing or active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
3. Patient with documented hypersensitivity to any of the components of the chemotherapy program.
4. Men and women of childbearing potential who do not practice contraception. Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation.

Cohort 2

Inclusion Criteria:

8\. Patients with previously untreated AML who are not currently eligible for other frontline clinical trials of AML therapy. Prior therapy with hydroxyurea, hematopoietic growth factors, azacytidine, ATRA, or total dose of cytarabine up to 2g is allowed. Patients with history of MDS transformed to AML are eligible regardless of their prior therapy for MDS provided this will be their first induction therapy for AML.

9\. Age \>/= 18 years who are unsuitable for standard induction therapy are eligible after discussion with PI 10. Patients must have one of the following:

* Creatinine \>/= 2 mg/dL
* Total bilirubin \>/= 2 mg/dL
* ECOG Performance Status equal to 3 or 4
* Is ineligible for participation in a protocol of higher priority 11. A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.

  12\. Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient is required prior to their enrollment on the protocol.

  13\. Prior therapy with decitabine will be allowed unless the patient experienced progression to AML while being treated with decitabine.

Exclusion Criteria:

5\. Pregnant women are excluded from this study because the agents used in this study have the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding should also be avoided.

6\. Uncontrolled intercurrent illness including, but not limited to ongoing or active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements, unless these illnesses are judged to be related to the underlying leukemia.

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

8\. Men and women of childbearing potential who do not practice contraception. Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation.

Cohort 3

Inclusion Criteria:

1. Patients with relapsed and or refractory AML who have received at least one prior therapy for their AML.
2. Age \>/= 18 years.
3. Adequate organ function as defined below:

   * liver function (bilirubin \< 2mg/dL, AST and/or ALT \<3 x ULN)
   * kidney function (creatinine \< 1.5 x ULN ).
4. ECOG performance status of ≤ 2.
5. A negative urine pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial.
6. Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient is required prior to their enrollment on the protocol.
7. Prior therapy with venetoclax will be allowed.

   Exclusion Criteria
8. Pregnant women are excluded from this study because the agents used in this study have the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding should also be avoided.
9. Uncontrolled intercurrent illness including, but not limited to ongoing or active uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
10. Patient with documented hypersensitivity to any of the components of the chemotherapy program.

Men and women of childbearing potential who do not practice contraception. Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation

Where this trial is running

Houston, Texas

• University of Texas MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Principal investigator: Tapan Kadia, MD — M.D. Anderson Cancer Center
• Study coordinator: Tapan Kadia, MD

Conditions Leukemia; Acute myeloid leukemia; AML; myelodysplastic syndrome; MDS; Cytarabine; Ara-C; Cytosar