Alvocidib, Cytarabine, and Mitoxantrone Hydrochloride or Cytarabine and Daunorubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

NCT01349972 | Completed Phase 2 Results

• 8 other identifiers: NCI-2011-02587JHOC-J1101CDR0000699421J11018972U01CA070095N01CM00100P30CA006973
• Study Type: interventional
• Target: 172
• Locations: 1 country
• Sites: 11

Brief Summary

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

Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate

  Bone marrow showing less than 5% myeloblasts with normal maturation of all cell lines, an ANC of at least 1000/cu mm and a platelet count of 100,000/cu mm, absence of blast in peripheral blood, absence of identifiable leukemic cells in the bone marrow, clearance of disease-associated cytogenetic abnormalities, and clearance of any previously existing extramedullary disease. These criteria are taken from Dohner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 2010;115:453-474

  3 years

Secondary Outcomes (5)

• Incidence of Toxicities, Characterized by Number of Events by Treatment and Grade

  Up to 14 days after completion of study treatment

• Disease-free Survival

  Time from randomization until death from any cause or relapse or recurrence, assessed up to 2 years

• Overall Survival

  4 years

• Number of Patients With Minimal Residual Disease

  From study start to 14 days after the start of treatment

• Progression-free Survival

  4 years

Study Arms (2)

Arm I (alvocidib, cytarabine, mitoxantrone hydrochloride)

EXPERIMENTAL

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.

Drug: alvocidib; Drug: mitoxantrone hydrochloride; Drug: cytarabine

Arm II (cytarabine, daunorubicin hydrochloride)

ACTIVE COMPARATOR

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.

Drug: daunorubicin hydrochloride; Drug: cytarabine

Interventions

alvocidib DRUG

Given IV

Also known as: FLAVO, flavopiridol, HMR 1275, L-868275

Arm I (alvocidib, cytarabine, mitoxantrone hydrochloride)

daunorubicin hydrochloride DRUG

Given IV

Also known as: Cerubidin, Cerubidine, daunomycin hydrochloride, daunorubicin, RP-13057

Arm II (cytarabine, daunorubicin hydrochloride)

mitoxantrone hydrochloride DRUG

Given IV

Also known as: CL 232315, DHAD, DHAQ

Arm I (alvocidib, cytarabine, mitoxantrone hydrochloride)

cytarabine DRUG

Given IV

Also known as: ARA-C, arabinofuranosylcytosine, arabinosylcytosine, Cytosar-U, cytosine arabinoside

Arm I (alvocidib, cytarabine, mitoxantrone hydrochloride); Arm II (cytarabine, daunorubicin hydrochloride)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (11)

Mayo Clinic Scottsdale-Phoenix

Scottsdale, Arizona, 85259, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Blood and Marrow Transplant Group of Georgia

Atlanta, Georgia, 30342, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University/Sidney Kimmel Comprehensive Cancer Center

Baltimore, Maryland, 21287, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

Related Publications (2)

• Zeidner 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 RESULT

• Gerber 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 DERIVED

Related Links

• Pubmed

MeSH Terms

Conditions

Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Congenital Abnormalities; Leukemia, Myelomonocytic, Acute; Leukemia, Erythroblastic, Acute

Interventions

alvocidib; Daunorubicin; Mitoxantrone; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Myeloproliferative Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Anthraquinones; Anthrones; Anthracenes; Quinones; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Joshua Zeidner
• Organization: University of North Carolina, Lineberger Comprehensive Cancer Center

Joshua_Zeidner@med.unc.edu

(919) 962-5164

Study Officials

• B. Smith

  Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2011
• First Posted: May 9, 2011
• Study Start: April 1, 2011
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: July 31, 2017
• Results First Posted: June 6, 2017

Record last verified: 2017-07

Locations

US (11)