Clinical trial · Interventional
Alvocidib, Cytarabine, and Mitoxantrone Hydrochloride or Cytarabine and Daunorubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia
Randomized Phase II Trial of Timed Sequential Therapy (TST) With Alvocidib (Flavopiridol), Ara-C and Mitoxantrone (FLAM) vs. "7+3" for Adults Age 70 and Under With Newly Diagnosed Acute Myelogenous Leukemia (AML)
- 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 randomized phase II trial is studying how alvocidib, cytarabine, and mitoxantrone hydrochloride work compared to cytarabine and daunorubicin hydrochloride in treating patients with newly diagnosed acute myeloid leukemia. Alvocidib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine, mitoxantrone hydrochloride, and daunorubicin hydrochloride work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving alvocidib, cytarabine, and mitoxantrone hydrochloride is more effective than giving cytarabine and daunorubicin hydrochloride in treating patients with acute myeloid leukemia.
Conditions
Conditions (16)
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 Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome | Acute Myeloid Leukemia Arising from Previous Myelodysplastic Syndrome | ALIAS | 0.90 |
| Adult Acute Minimally Differentiated Myeloid Leukemia (M0) | Adult Acute Myeloid Leukemia with Minimal Differentiation | ALIAS | 0.90 |
| Adult Acute Monoblastic Leukemia (M5a) | Adult Acute Monoblastic Leukemia | ONTOLOGY_EXACT | 0.85 |
| Adult Acute Monocytic Leukemia (M5b) | Adult Acute Monocytic Leukemia | ONTOLOGY_EXACT | 0.85 |
| Adult Acute Myeloblastic Leukemia With Maturation (M2) | Adult Acute Myeloid Leukemia with Maturation | ALIAS | 0.90 |
| Adult Acute Myeloblastic Leukemia Without Maturation (M1) | Adult Acute Myeloid Leukemia without Maturation |
Interventions
Interventions (4)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| alvocidib | Drug | Alvocidib | ALIAS |
| cytarabine | Drug | Cytarabine | ALIAS |
| daunorubicin hydrochloride | Drug | Daunorubicin | ALIAS |
| mitoxantrone hydrochloride | Drug | Mitoxantrone | ALIAS |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Arm I (alvocidib, cytarabine, mitoxantrone hydrochloride)
- description
- Patients receive alvocidib IV over 1 hour on days 1-3, cytarabine IV over 72 hours on days 6-8, and mitoxantrone hydrochloride IV over 1-2 hours on day 9. Patients who achieve complete or partial response to the first course (completion of all doses) may receive a second course of treatment or high-dose cytarabine after 21-63 days following blood count recovery, and/or undergo allogeneic bone marrow transplant.
- interventionNames
- Drug: alvocidib
- Drug: mitoxantrone hydrochloride
- Drug: cytarabine
- type
- ACTIVE_COMPARATOR
- label
- Arm II (cytarabine, daunorubicin hydrochloride)
- description
- Patients receive cytarabine IV continuously on days 1-7 and daunorubicin hydrochloride IV on days 1-3. Patients who have residual disease on day 14 may receive additional cytarabine for 5 days and daunorubicin hydrochloride for 2 days.
- interventionNames
- Drug: daunorubicin hydrochloride
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 70 Years
Show eligibility criteria text
Inclusion Criteria: * All adults with established, pathologically confirmed diagnoses of newly diagnosed AML and adults with newly diagnosed AML, excluding newly diagnosed core-binding factor (CBF) AMLs and acute progranulocytic leukemia (APL, M3), will be considered eligible for study * Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-3 * Patients \>= 65 years of age must have ECOG PS =\< 2 prior to developing leukemic symptoms * Serum creatinine ≤ 2.0 mg/dL * Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =\< 5 times upper limit of normal (ULN) (unless leukemic infiltration) * Total bilirubin =\< 2.0 mg/dL (unless Gilbert disease, hemolysis, or leukemia) * Left ventricular ejection fraction ≥ 45% * Newly diagnosed AML, subtypes M0, 1, 2, 4-7 but excluding M3 (APL), including those with the following poor risk features: * Antecedent hematologic disorder including myelodysplasia (MDS)-related AML (MDS/AML) and prior myeloproliferative disorder (MPD) * Treatment-related myeloid neoplasms (t-AML/t-MDS) * Myeloid sarcoma, myeloid proliferations related to Down Syndrome, and blastic plasmacytoid dendritic cell neoplasm * AML with multilineage dysplasia (AML-MLD) * Adverse cytogenetics (defined as -5/-5q; -7/-7q; abnormal 3q, 9q, 11q, 20q, 21q, or 17p; t(6;9); t(9;22); trisomy 8; trisomy 13; trisomy 21; and complex karyotypes (≥ 3 unrelated abnormalities) * Patients who have received hydroxyurea alone or have received non-cytotoxic therapies previously for myelodysplasia (MDS) or myeloproliferative disorder (MPD) (e.g., thalidomide or lenalidomide, interferon, cytokines, 5-azacytidine or decitabine, histone deacetylase inhibitors, low-dose cyclophosphamide \[cytoxan\], tyrosine kinase \[TK\] or dual TK/src inhibitors) will be eligible for this trial * At least 24 hours since prior leukopheresis or hydroxyurea for cytoreduction Exclusion Criteria: * Any previous treatment with flavopiridol * Concomitant chemotherapy, radiation therapy, or immunotherapy * Hyperleukocytosis with \>= 50,000 blasts/uL; leukopheresis or hydroxyurea may be used immediately prior to study drug administration for cytoreduction; must be stopped 24 hours before first dose of study chemotherapy * CBF AMLs associated with t(8;21) or M4eo subtype (inv\[16\] or t\[16;16\]), as diagnosed by morphologic criteria, flow cytometric characteristics, and rapid cytogenetics or FISH or molecular testing * Acute Progranulocytic Leukemia (APL, M3) * Active central nervous system (CNS) leukemia * Active, uncontrolled infection; patients with infection under active treatment and controlled with antibiotics are eligible * Active, uncontrolled graft vs. host disease (GVHD) following allogeneic transplant for non-AML condition (e.g. MDS, lymphoid malignancy, aplastic anemia); patients with GVHD controlled on stable doses of immunosuppressants are eligible * Presence of other life-threatening illness * Patients with mental deficits and/or psychiatric history that preclude them form giving informed consent or from following protocol * Pregnant and nursing patients are excluded
References
Publications (2)
- RESULTZeidner JF, Foster MC, Blackford AL, Litzow MR, Morris LE, Strickland SA, Lancet JE, Bose P, Levy MY, Tibes R, Gojo I, Gocke CD, Rosner GL, Little RF, Wright JJ, Doyle LA, Smith BD, Karp JE. Randomized multicenter phase II study of flavopiridol (alvocidib), cytarabine, and mitoxantrone (FLAM) versus cytarabine/daunorubicin (7+3) in newly diagnosed acute myeloid leukemia. Haematologica. 2015 Sep;100(9):1172-9. doi: 10.3324/haematol.2015.125849. Epub 2015 May 28. PMID 26022709
- DERIVEDGerber JM, Zeidner JF, Morse S, Blackford AL, Perkins B, Yanagisawa B, Zhang H, Morsberger L, Karp J, Ning Y, Gocke CD, Rosner GL, Smith BD, Jones RJ. Association of acute myeloid leukemia's most immature phenotype with risk groups and outcomes. Haematologica. 2016 May;101(5):607-16. doi: 10.3324/haematol.2015.135194. Epub 2016 Jan 27. PMID 26819054