Cladribine Plus Low Dose Cytarabine (LDAC) Alternating With Decitabine in Patients With Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndrome (MDS)

January 16, 2024 updated by: M.D. Anderson Cancer Center

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)

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 disease in patients with AML or MDS. The safety of this drug combination will also be studied.

Cladribine is designed to interfere with the cell's ability to process DNA (the genetic material of cells). It can also insert itself into the DNA of cancer cells to stop them from growing and repairing themselves.

Cytarabine is designed to insert itself into DNA of cancer cells to stop them from growing and repairing themselves.

Decitabine is designed to damage the DNA of cells, which may cause cancer cells to die.

This is an investigational study. Cladribine is FDA approved and commercially available for use in patients with hairy cell leukemia. Its use in patients with AML is investigational.

Cytarabine is FDA approved and commercially available for use in patients with AML.

Decitabine is FDA approved and commercially available for use in patients with MDS. Its use for patients with AML is investigational.

Up to 160 patients will take part in this study. All will be enrolled at MD Anderson.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Study Drug Administration:

If you are eligible to take part in this study, you will receive 1 or 2 cycles of induction therapy followed by up to 17 cycles of consolidation therapy. Each study cycle is 4 weeks.

Induction Cycles:

On Days 1-5, you will receive cladribine by vein over 1-2 hours.

On Days 1-10, you will give yourself the cytarabine by injection twice a day about 12 hours apart. You will receive instructions on how give yourself the injections.

You may receive up to 2 cycles at this dose and schedule.

Consolidation Cycles:

Consolidation cycles will begin on Cycle 2 regardless of how many cycles you received of induction therapy.

During Cycles 2, 5, 6, 9, 10, 13, 14, 17, and 18:

  • On Days 1-3, you will receive cladribine by vein over 1-2 hours.
  • On Days 1-10, you will give yourself cytarabine by injection twice daily starting 3 to 6 hours after the start of the cladribine infusion.

Cycles 3, 4, 7, 8, 11, 12, 15, and 16:

°On Days 1-5, you will receive decitabine by vein over 1-2 hours each day.

Length of Treatment:

You may continue taking the study drugs for up to 18 cycles. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Your participation on the study will be over when you have completed follow-up.

Study Visits:

On Day 1 of every cycle:

  • You will have a physical exam, including measurement of your weight and vital signs.
  • Your performance status will be recorded.

On Day 21 (+/- 7days) of the induction cycle, you may have a bone marrow aspirate to check the status of the disease. After that, you will have a bone marrow aspirate every 2 weeks (or more often if your doctor feels it is necessary). If your routine blood tests show that there is still leukemia, you may not need to have the bone marrow samples collected.

Blood (about 1-2 teaspoons) will be drawn for routine tests at least 1 time weekly until remission, then every 2-4 weeks during treatment, the every 4-8 weeks while you are on the study.

Follow-Up Visits:

When you are off treatment, every 6 -12 months you will be contacted by a member of the study staff. You will be asked about any side effects you may be having. The phone calls will take about 5-10 minutes. You will continue to be called for as long as possible.

Study Type

Interventional

Enrollment (Estimated)

160

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • University of Texas MD Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cladribine + Cytarabine Alt. with Decitabine

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.
Drug: Cladribine

Induction cycle: 5 mg/m2 by vein on days 1 - 5 for up to 2, 28 day cycles.

Consolidation cycle: 5 mg/m2 by vein on days 1 - 3 of cycles 2, 5, 6, 9, 10, 13, 14, 17, and 18.

Other Names:
  • 2-CdA
  • Leustatin
Drug: Cytarabine

Induction cycle: 20 mg subcutaneously twice daily on days 1-10 for up to 2, 28 day cycles.

Consolidation cycle: 20 mg subcutaneously twice daily on days 1 - 10 of cycles 2, 5, 6, 9, 10, 13, 14, 17, and 18.

Other Names:
  • Ara-C
  • Cytosine Arabinosine Hydrochloride
  • Cytosar DepoCyt
Drug: Decitabine
Consolidation cycle: 20 mg/m2 by vein over 1 to 2 hours on days 1-5 of cycles 3, 4, 7, 8, 11, 12, 15, and 16.
Other Names:
  • Dacogen

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Disease-Free Survival (DFS)
Time Frame: Day 21
Disease-free survival (DFS) defined as the time interval from treatment start until clinically significant disease progression or death, whichever occurred first. Participants followed for survival every 6 to 12 months after completion of active treatment. Study continuously monitored for primary endpoint, DFS using the method of Thall, Wooten, and Tannir.
Day 21

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Investigators

  • Principal Investigator: Tapan Kadia, MD, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 7, 2012

Primary Completion (Estimated)

February 1, 2026

Study Completion (Estimated)

February 1, 2026

Study Registration Dates

First Submitted

January 13, 2012

First Submitted That Met QC Criteria

January 18, 2012

First Posted (Estimated)

January 24, 2012

Study Record Updates

Last Update Posted (Estimated)

January 17, 2024

Last Update Submitted That Met QC Criteria

January 16, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2011-0987
  • NCI-2012-00145 (Registry Identifier: NCI CTRP)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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