Refractory Acute LeukemiaPhase 1NCT06474663
A Phase I Study Investigating the Combination of Cladribine, Low Dose Cytarabine and Sorafenib Alternating With Decitabine in Pediatric Relapsed and Refractory Acute Leukemias
A Phase 1 study testing Cladribine, Cytarabine and Sorafenib in people with Refractory Acute Leukemia and Relapsed Acute Leukemia, run by M.D. Anderson Cancer Center.
Trial summary
To find the recommended dose of the drug combination cladribine, cytarabine, decitabine, and sorafenib in participants with relapsed/refractory AML, MPAL, and ALAL. Read more about this study
- Who is it for?
- Ages 1 year to 21 years
- Conditions the study is for
- Refractory Acute Leukemia, Relapsed Acute Leukemia
- What is being tested?
- Cladribine, Cytarabine and Sorafenib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 31 Jul 2025to 31 Jul 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Age ≥ 1 year to 21 years
- ECOG performance status of ≥ 2.
- Relapsed21/refractory: AML22 or Mixed phenotype acute leukemia (MPAL) patients /Acute leukemia of ambiguous lineage (ALAL) with.
- ≥1% leukemic blasts in the bone marrow:
- As detected by MRD testing ≥ 25% or MRD is ≥ 5% with 1 additional sensitive diagnostic test demonstrating .1% blasts (NGS-MRD (clonoSeq23) or FISH or cytogenetics or RT-PCR of leukemic specific marker or M2/M3 morphology); or MRD is ≥ 1% with 2 additional sensitive diagnostic tests demonstrating ≥1% blasts.
- If the MRD is ≥ 1% but without the required confirmatory tests, then a relapse can still be defined if a consecutive marrow evaluation separated by ≥1 week demonstrates. ≥ 1% using 2 sensitive diagnostic tests.
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- If MRD testing is unavailable, then a single marrow is sufficient to define relapse if M3 morphology or M2 morphology with 1 additional sensitive diagnostic test demonstrating ≥1% blasts (FISH or cytogenetics or RT-PCR of leukemic specific marker) or M1 morphology with 2 additional sensitive diagnostic tests demonstrating. ≥1% blasts is present.
- If the morphology is M2 with no confirmatory tests, then a relapse can still be defined if a consecutive marrow evaluation separated by ≥ 1 week demonstrates M2 morphology.
- Marrow definitions: M2 marrow ≥ 5 to <25% blasts; M3 marrow ≥ 25% blasts
- WBC must be below 25,000/ ƒÊL at time of enrollment. Patients may receive cytoreduction prior to enrollment.
- Baseline ejection fraction must be > 40%.
- Adequate hepatic function (direct bilirubin < 1.5x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement, and AST and/or ALT < 5x ULN unless considered due to leukemic involvement, in which case direct bilirubin or AST and/or ALT < 5x ULN will be considered eligible).
- Adequate renal function (creatinine clearance ≥ 30 mL/min) unless related to disease. (Justification on page 7-8)
- In the absence of rapidly proliferative disease, the interval from prior treatment to time of initiation will be at least 14 days for cytotoxic or non-cytotoxic (immunotherapy agent(s), or an interval of 5 half-lives of the prior therapy. Oral hydroxyurea and/or cytarabine (up to 2 g/m2) for patients with rapidly proliferative disease is allowed before the start of study therapy, as needed, for clinical benefit and after discussion with the PI. Concurrent therapy for central nervous system (CNS) prophylaxis or continuation of therapy for controlled CNS disease is permitted.
- Unless surgically or biologically sterile: Women of childbearing potential must agree to adequate methods of contraception during the study and at least 3 months for males, and 6 months for females, after the last treatment.
Who cannot join
- Participants who weigh less than 10kg.
- Participants with any concurrent uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place the participant at unacceptable risk of study treatment.
- The use of other chemotherapeutic agents or anti-leukemic agents is not permitted during study with the following exceptions (1) intrathecal chemotherapy for prophylactic use or for controlled CNS leukemia. (2) use of hydroxyurea for patients with rapidly proliferative disease or for control of counts during differentiation syndrome. (3) use of steroids for treatment of differentiation syndrome.
- Participants with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications.
- Participants with a concurrent active malignancy under treatment.
- Known active hepatitis B (HBV) or Hepatitis C (HCV) infection or known HIV infection.
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- Female participants who are pregnant or breast-feeding.
- Participants has an active uncontrolled infection.
- History of or any concurrent condition, therapy, or laboratory abnormality that in the Investigator's opinion might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the participants.
About this study
To find the recommended dose of the drug combination cladribine, cytarabine, decitabine, and sorafenib in participants with relapsed/refractory AML, MPAL, and ALAL.
Read the detailed description
Primary Objectives - To determine the safety, tolerability, and recommended phase II dose (RP2D) of the combination of cladribine, low-dose cytarabine, sorafeneib alternating with decitabine for pediatric participants with acute leukemias.
Secondary Objectives
- To determine the preliminary assessment of efficacy by overall response (OR), including complete remission (CR), CR with partial hematological recovery (CRh), CR with incomplete blood count recovery (CRi), Morphologic leukemia free state (MLFS) and partial remission (PR), overall survival (OS), event-free survival (EFS) and duration of response (DOR) of pediatric participants treated with this combination.
- Conditions
- Refractory Acute Leukemia, Relapsed Acute Leukemia
- Being tested
- Cladribine, Cytarabine, Sorafenib, Decitabine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CladribineDrug
Also called Leustatin®, 2-CdA
Given by IV
CytarabineDrug
Also called Ara-C, Cytosar®, DepoCyt™, Cytosine arabinosine hydrochloride
Given by SC
SorafenibDrug
Also called Nexavar®, BAY 43-9006
Given by PO
DecitabineDrug
Given by IV
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 | Experimental | Participants enrolled in Phase 1, the dose level of cladribine, cytarabine, decitabine, and sorafenib will depend on when you join this study. Up to 2 dose levels of this drug combination may be tested. Between 3-6 participants will be enrolled in each dose level. The first group of participants will receive the starting dose level of this drug combination. If no intolerable side effects are seen, the next group of participants will receive the higher dose level of this drug combination. Receives: Drug: Cladribine; Drug: Cytarabine; Drug: Sorafenib; Drug: Decitabine |
| Dose Expansion | Experimental | Participants enrolled in Dose Expansion, you will receive cladribine, cytarabine, decitabine, and sorafenib at the recommended dose level found in Phase 1. Receives: Drug: Cladribine; Drug: Cytarabine; Drug: Sorafenib; Drug: Decitabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and adverse events (AEs)
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Measured: Through study completion; an average of 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2024
- Study start31 Jul 2025
- Primary completion31 Jul 2025
- Study completion31 Jul 2025
Why it stopped: 0 participants
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory Acute LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Branko Cuglievan, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06474663
- Sponsor's protocol ID
- 2024-0302
- Other IDs
- NCI-2024-05386
- Status last verified
- Jul 2025
- First submitted
- 20 Jun 2024
- Last updated
- 6 Aug 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study Investigating the Combination of Cladribine, Low Dose Cytarabine and Sorafenib Alternating With Decitabine in Pediatric Relapsed and Refractory Acute Leukemias
- ClinicalTrials.gov ID
- NCT06474663
- Acronym / sponsor ID
- 2024-0302
- Conditions
- Refractory Acute Leukemia, Relapsed Acute Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: 0 participants
- Enrolment
- 0 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Study start
- 31 Jul 2025 (actual)
- Primary completion
- 31 Jul 2025 (actual)
- Study completion
- 31 Jul 2025 (actual)
- First posted
- 26 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To find the recommended dose of the drug combination cladribine, cytarabine, decitabine, and sorafenib in participants with relapsed/refractory AML, MPAL, and ALAL.
Detailed description
Primary Objectives - To determine the safety, tolerability, and recommended phase II dose (RP2D) of the combination of cladribine, low-dose cytarabine, sorafeneib alternating with decitabine for pediatric participants with acute leukemias.
Secondary Objectives
- To determine the preliminary assessment of efficacy by overall response (OR), including complete remission (CR), CR with partial hematological recovery (CRh), CR with incomplete blood count recovery (CRi), Morphologic leukemia free state (MLFS) and partial remission (PR), overall survival (OS), event-free survival (EFS) and duration of response (DOR) of pediatric participants treated with this combination.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase 1 | Experimental | Drug: Cladribine, Drug: Cytarabine, Drug: Sorafenib, Drug: DecitabineParticipants enrolled in Phase 1, the dose level of cladribine, cytarabine, decitabine, and sorafenib will depend on when you join this study. Up to 2 dose levels of this drug combination may be tested. Between 3-6 participants will be enrolled in each dose level. The first group of participants will receive the starting dose level of this drug combination. If no intolerable side effects are seen, the next group of participants will receive the higher dose level of this drug combination. |
| Dose Expansion | Experimental | Drug: Cladribine, Drug: Cytarabine, Drug: Sorafenib, Drug: DecitabineParticipants enrolled in Dose Expansion, you will receive cladribine, cytarabine, decitabine, and sorafenib at the recommended dose level found in Phase 1. |
Who may qualify
- Ages
- 1 year to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (15 listed)
- Age ≥ 1 year to 21 years
- ECOG performance status of ≥ 2.
- Relapsed21/refractory: AML22 or Mixed phenotype acute leukemia (MPAL) patients /Acute leukemia of ambiguous lineage (ALAL) with.
- WBC must be below 25,000/ ƒÊL at time of enrollment. Patients may receive cytoreduction prior to enrollment.
- Baseline ejection fraction must be > 40%.
Key exclusion criteria (9 listed)
- Participants who weigh less than 10kg.
- Participants with any concurrent uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place the participant at unacceptable risk of study treatment.
- The use of other chemotherapeutic agents or anti-leukemic agents is not permitted during study with the following exceptions (1) intrathecal chemotherapy for prophylactic use or for controlled CNS leukemia. (2) use of hydroxyurea for patients with rapidly proliferative disease or for control of counts during differentiation syndrome. (3) use of steroids for treatment of differentiation syndrome.
- Participants with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications.
- Participants with a concurrent active malignancy under treatment.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CladribineAlso: Leustatin®, 2-CdAGiven by IV | Drug | Dose Expansion, Phase 1 |
| CytarabineAlso: Ara-C, Cytosar®, DepoCyt™, Cytosine arabinosine hydrochlorideGiven by SC | Drug | Dose Expansion, Phase 1 |
| SorafenibAlso: Nexavar®, BAY 43-9006Given by PO | Drug | Dose Expansion, Phase 1 |
| DecitabineGiven by IV | Drug | Dose Expansion, Phase 1 |
Primary outcome
Safety and adverse events (AEs)
Time frame: Through study completion; an average of 1 year
Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2025.
- MD Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Branko Cuglievan, MD principal investigator
M.D. Anderson Cancer Center
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cladribine, Cytarabine and Sorafenib in people with Refractory Acute Leukemia and Relapsed Acute Leukemia, run by M.D. Anderson Cancer Center.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 6 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and adverse events (AEs) (time frame: Through study completion; an average of 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Aug 2025.