A Phase I Study Investigating the Combination of Cladribine, Low Dose Cytarabine and Sorafenib Alternating With Decitabine in Pediatric Relapsed and Refractory Acute Leukemias

To find the recommended dose of the drug combination cladribine, cytarabine, decitabine, and sorafenib in participants with relapsed/refractory AML, MPAL, and ALAL.

Study Overview

• Status: Withdrawn
• Conditions: Refractory Acute Leukemia; Relapsed Acute Leukemia
• Intervention / Treatment: Drug: Decitabine; Drug: Cladribine; Drug: Cytarabine; Drug: Sorafenib

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 Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age ≥ 1 year to 21 years
2. ECOG performance status of ≥ 2.

3. Relapsed21/refractory: AML22 or Mixed phenotype acute leukemia (MPAL) patients /Acute leukemia of ambiguous lineage (ALAL) with.

   1. ≥1% leukemic blasts in the bone marrow:
   2. 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.

   i. 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.

   ii. 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.

   iii. 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.

   c. Marrow definitions: M2 marrow ≥ 5 to <25% blasts; M3 marrow ≥ 25% blasts

4. WBC must be below 25,000/ ƒÊL at time of enrollment. Patients may receive cytoreduction prior to enrollment.
5. Baseline ejection fraction must be > 40%.
6. 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).
7. Adequate renal function (creatinine clearance ≥ 30 mL/min) unless related to disease. (Justification on page 7-8)
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.
9. 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.

Exclusion Criteria:

1. Participants who weigh less than 10kg.
2. Participants with any concurrent uncontrolled medical condition, laboratory abnormality, or psychiatric illness which could place the participant at unacceptable risk of study treatment.
3. 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.
4. Participants with any severe gastrointestinal or metabolic condition which could interfere with the absorption of oral study medications.
5. Participants with a concurrent active malignancy under treatment.
6. Known active hepatitis B (HBV) or Hepatitis C (HCV) infection or known HIV infection.
7. Female participants who are pregnant or breast-feeding.
8. Participants has an active uncontrolled infection.
9. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1; 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.	Drug: Decitabine; Given by IV; Drug: Cladribine; Given by IV; Other Names: Leustatin®; 2-CdA; Drug: Cytarabine; Given by SC; Other Names: Ara-C; Cytosine arabinosine hydrochloride; Cytosar®; DepoCyt™; Drug: Sorafenib; Given by PO; Other Names: Nexavar®; BAY 43-9006
Experimental: Dose Expansion; Participants enrolled in Dose Expansion, you will receive cladribine, cytarabine, decitabine, and sorafenib at the recommended dose level found in Phase 1.	Drug: Decitabine; Given by IV; Drug: Cladribine; Given by IV; Other Names: Leustatin®; 2-CdA; Drug: Cytarabine; Given by SC; Other Names: Ara-C; Cytosine arabinosine hydrochloride; Cytosar®; DepoCyt™; Drug: Sorafenib; Given by PO; Other Names: Nexavar®; BAY 43-9006

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Through study completion; an average of 1 year

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Investigators: Principal Investigator: Branko Cuglievan, MD, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2025
• Primary Completion (Actual): July 31, 2025
• Study Completion (Actual): July 31, 2025

Study Registration Dates

• First Submitted: June 20, 2024
• First Submitted That Met QC Criteria: June 20, 2024
• First Posted (Actual): June 26, 2024

Study Record Updates

• Last Update Posted (Actual): August 6, 2025
• Last Update Submitted That Met QC Criteria: August 1, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Hematologic Diseases; Leukemia; Acute Disease; Anti-Infective Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antiviral Agents; Protein Kinase Inhibitors; Decitabine; Sorafenib; Cytarabine; Cladribine
• Other Study ID Numbers: 2024-0302; NCI-2024-05386 (Other Identifier: NCI-CTRP Clinical Registry)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No