Clinical trial · Interventional
Filgrastim, Cladribine, Cytarabine, and Mitoxantrone With Sorafenib in Treating Patients With Newly-Diagnosed, Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
Addition of Sorafenib to G-CSF, Cladribine, Cytarabine and Mitoxantrone (G-CLAM) in Adults With Newly-Diagnosed Acute Myeloid Leukemia (AML) Independent of FLT3-ITD Status: A Phase 1/2 Study
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This phase I/II trial studies the side effects and best dose of filgrastim (granulocyte colony-stimulating factor \[G-CSF\]), cladribine, cytarabine, and mitoxantrone, when given together with sorafenib and to see how well they work in treating patients with newly-diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome (likely to be more aggressive). Drugs used in chemotherapy, such as cladribine, cytarabine, and mitoxantrone work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Colony-stimulating factors, such as filgrastim, may increase the production of blood cells and may help the immune system recover from the side effects of chemotherapy. Sorafenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving filgrastim, cladribine, cytarabine, and mitoxantrone together with sorafenib may kill more cancer cells.
Conditions
Conditions (5)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Acute Biphenotypic Leukemia | Acute Biphenotypic Leukemia | ONTOLOGY_EXACT | 0.90 |
| Acute Myeloid Leukemia | Acute Myeloid Leukemia | CURATED_BROADER | 0.80 |
| de Novo Myelodysplastic Syndrome | De Novo Myelodysplastic Syndrome | ONTOLOGY_EXACT | 0.98 |
| Myelodysplastic Syndrome | Myelodysplastic Syndrome | CURATED_BROADER | 0.80 |
| Myeloproliferative Neoplasm | Myeloproliferative Neoplasm | CURATED_BROADER | 0.80 |
Interventions
Interventions (7)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Cladribine | Drug | Cladribine | ALIAS |
| Cytarabine | Drug | Cytarabine | ALIAS |
| Filgrastim | Biological | Filgrastim | ALIAS |
| Laboratory Biomarker Analysis | Other | — | UNRESOLVED |
| Mitoxantrone | Drug | Mitoxantrone | ALIAS |
| Quality-of-Life Assessment | Other | — | UNRESOLVED |
| Sorafenib | Drug | Sorafenib | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- Treatment (sorafenib, G-CLAM)
- description
- See Detailed Description.
- interventionNames
- Drug: Cladribine
- Drug: Cytarabine
- Biological: Filgrastim
- Other: Laboratory Biomarker Analysis
- Other: Quality-of-Life Assessment
- Drug: Mitoxantrone
- Drug: Sorafenib
Primary outcomes (3)
- measure
- Phase 1: Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of Mitoxantrone
- timeFrame
- First 28 days of treatment
- description
- MTD/RP2D will be defined as the highest dose studied in which the incidence of dose-limiting toxicity (DLT) is \< 33% assuming at least 6 patients have been treated at this dose. DLTs were defined as: 1) grade ≥3 non-hematologic toxicity lasting \>48 hours leading to \>7-day delay of the next cycle; 2) grade ≥4 non-hematologic toxicity if no recovery to grade ≤2 in 14 days (both excluding febrile neutropenia/ infection); 3) Absolute neutrophil count \<500/ µL or platelet count \<50,000/µL for \>49 days after CLAGM+S without marrow evidence of AML. Doses were escalated up to dose level six if \<2/6 patients out of each cohort of 6 had a DLT (some cohorts were expanded to 12 patients while awaiting completion of DLT monitoring period). The dose level at which dose escalation was stopped was the recommended phase 2 dose (RP2D).
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 60 Years
Show eligibility criteria text
Inclusion Criteria: * Age 18-60 years, inclusive * Newly diagnosed disease with either a diagnosis of "high-risk" MDS (\>= 10% blasts in marrow or blood), high-risk myeloproliferative neoplasm (MPN; \>= 10% blasts in blood or bone marrow), or AML other than acute promyelocytic leukemia (APL) with t(15;17)(q22;q12) or variants according to the 2008 World Health Organization (WHO) classification. Patients with biphenotypic AML are eligible; such "high-risk" MDS or MPN have natural history much closer to AML than to lower risk MDS or MPN and have responded similarly to "AML-type" therapy. * Outside diagnostic material is acceptable as long as peripheral blood and/or bone marrow slides are reviewed at the study institution by appropriate clinical staff. Flow cytometric analysis of peripheral blood and/or bone marrow should be performed according to institutional practice guidelines. * Treatment-related mortality (TRM) score =\< 13.1 as calculated with simplified model * The use of hydroxyurea prior to study registration is allowed. Patients with symptoms/signs of hyperleukocytosis, white blood cell (WBC) \> 100,000/uL, or acute symptoms can be treated with leukapheresis or may receive up to 2 doses of cytarabine (up to 500 mg/m\^2/dose) prior to study day 0 enrollment * Bilirubin =\< 2 times institutional upper limit of normal unless elevation is thought to be due to hepatic infiltration by AML, Gilbert's syndrome, or hemolysis (assessed within 10 days prior to study day 0) * Serum creatinine =\< 2.0 mg/dL (assessed within 10 days prior to study day 0) * Left ventricular ejection fraction \>= 45%, assessed within 3 months prior to study day 0, e.g. by multi gated acquisition scan (MUGA) scan or echocardiography, or other appropriate diagnostic modality and no clinical evidence of congestive heart failure * Women of childbearing potential and men must agree to use adequate contraception beginning at the signing of the consent until at least 3 months after the last dose of study drug * Provide written informed consent (or legal representative) Exclusion Criteria: * Myeloid blast crisis of chronic myeloid leukemia (CML), unless patient is not considered candidate for CML-directed tyrosine kinase inhibitor treatment (excluding sorafenib) * Concomitant illness associated with a likely survival of \< 1 year * Active systemic fungal, bacterial, viral, or other infection, unless disease is under treatment with anti-microbials and/or controlled or stable (e.g. if specific, effective therapy is not available/feasible or desired \[e.g. chronic viral hepatitis, human immunodeficiency virus (HIV)\]). Patient needs to be clinically stable as defined as being afebrile and hemodynamically stable for 24-48 hours prior to study day 0, unless fever is thought to be secondary to the underlying hematologic disease. * Active or clinically significant (or symptomatic) cardiac disease, including active coronary artery disease, cardiac arrhythmias requiring anti-arrhythmic therapy other than beta blockers or digoxin within the last 3 months, unstable angina (anginal symptoms at rest), new-onset angina within 3 months before randomization, or myocardial infarction within 6 months before study day 0 * Previous receipt of azacitidine, decitabine, anthracyclines, cytarabine, or other nucleoside analogues for treatment of AML or MPN/MDS other than as noted for cytarabine * Pregnancy or lactation * Concurrent treatment with any other investigational agent that has anti-leukemia activity or another drug with anti-AML-activity
References
Publications (1)
- DERIVEDHalpern AB, Rodriguez-Arboli E, Othus M, Garcia KA, Percival MM, Cassaday RD, Oehler VG, Becker PS, Appelbaum JS, Abkowitz JL, Orozco JJ, Keel SB, Hendrie PC, Scott BL, Ghiuzeli MC, Estey EH, Walter RB. Phase 1/2 study of sorafenib added to cladribine, high-dose cytarabine, G-CSF, and mitoxantrone in untreated AML. Blood Adv. 2023 Sep 12;7(17):4950-4961. doi: 10.1182/bloodadvances.2023010392. PMID 37339483