NCT01802333|CompletedPhase 3ResultsDMC

Cytarabine and Daunorubicin Hydrochloride or Idarubicin and Cytarabine With or Without Vorinostat in Treating Younger Patients With Previously Untreated Acute Myeloid Leukemia

A Randomized Phase III Study of Standard Cytarabine Plus Daunorubicin (7+3) Therapy or Idarubicin With High Dose Cytarabine (IA) Versus IA With Vorinostat (NSC-701852) (IA + V) in Younger Patients With Previously Untreated Acute Myeloid Leukemia (AML)

National Cancer Institute (NCI)ClinicalTrials.gov

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6 other identifiers

NCI-2013-00490S1203PS1203_A06PAMDREVW01SWOG-S1203U10CA180888U10CA032102

Study Type

interventional

Target

754

Locations

2 countries

Sites

447

Timeline

RegisteredMar 2013

StartedFeb 2013

CompletionJun 2017

Brief Summary

This randomized phase III trial studies cytarabine and daunorubicin hydrochloride or idarubicin and cytarabine with or without vorinostat to see how well they work in treating younger patients with previously untreated acute myeloid leukemia. Drugs used in chemotherapy, such as cytarabine, daunorubicin hydrochloride, idarubicin, and vorinostat, work in different ways to stop the growth of cancer cells, either by killing the cells, stopping them from dividing, or by stopping from spreading. Giving more than one drug (combination chemotherapy) and giving the drugs in different doses and in different combinations may kill more cancer cells. It is not yet known which combination chemotherapy is more effective in treating acute myeloid leukemia.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

754

participants targeted

Target at P75+ for phase_3

Timeline

Completed

Started Feb 2013

Typical duration for phase_3

Geographic Reach

2 countries

447 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

4.3 years study duration

Study Start

First participant enrolled

February 12, 2013

Completed

15 days until next milestone

First Submitted

Initial submission to the registry

February 27, 2013

Completed

2 days until next milestone

First Posted

Study publicly available on registry

March 1, 2013

Completed

4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 15, 2017

Completed

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 15, 2017

Completed

1.5 years until next milestone

Results Posted

Study results publicly available

December 19, 2018

Completed

Last Updated

December 19, 2018

Status Verified

November 1, 2018

Enrollment Period

4.3 years

First QC Date

February 27, 2013

Results QC Date

May 21, 2018

Last Update Submit

November 28, 2018

Conditions

Acute Myeloid Leukemia Untreated Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

Event-free Survival (EFS)
EFS is calculated for all patients from the date of initial registration on study until the first of the following: death from any cause, relapse from remission (CR or CRi) or completion of protocol Induction/Re-Induction therapy without documentation of CR or CRi. 2-year EFS by arm will be estimated using the Kaplan-Meier method. EFS will be compared between Arm I and Arm III and between Arm II and Arm III using Cox proportional hazards regression.
EFS assessed for up to 5 years, 2 year EFS reported
Rate of Allogeneic HCT
The goal of the transplant objective is to determine whether it is possible to conduct allogeneic HCT on 60% or more of adults with high-risk AML in first complete remission (alternative). If 40% or fewer of high-risk patients in CR can be transplanted, the proposed transplant support system will not be considered feasible. A one-sided binomial test compared to the null transplant rate will be conducted.
Up to 5 years

Secondary Outcomes (3)

Disease-free Survival (DFS) Among High Risk Patients
DFS assessed for up to 5 years, 2 year DFS reported
EFS of Arm I Compared to Arm II
EFS assessed for up to 5 years, 2 year EFS reported
Frequency and Severity of Toxicities
Up to 5 years

Other Outcomes (6)

Prevalence of the Mutation NPM1 in Patients on This Study.
Baseline
Prevalence of the Mutations IDH1, IDH2, TET2, DMT3A in Patients on This Study
Baseline
Cytogenetic Risk Distribution of Patients on This Study
Baseline
+3 more other outcomes

Study Arms (3)

Arm I (standard dose cytarabine, daunorubicin hydrochloride)

EXPERIMENTAL

INDUCTION/RE-INDUCTION: Patients receive standard dose cytarabine IV continuously on days 1-7 and daunorubicin hydrochloride IV on days 1-3. Patients with residual blasts may receive re-induction treatment beginning on day 15. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy. CONSOLIDATION: Patients receive cytarabine IV over 3 hours every 12 hours on days 1, 3, and 5. TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or consolidation therapy.

Procedure: Allogeneic Hematopoietic Stem Cell TransplantationDrug: CytarabineDrug: Daunorubicin HydrochlorideOther: Laboratory Biomarker Analysis

Arm II (high-dose cytarabine, idarubicin)

EXPERIMENTAL

INDUCTION/RE-INDUCTION: Patients receive high dose cytarabine IV continuously on days 1-4 and idarubicin IV over 15 minutes on days 1-3. Patients with residual blasts may receive re-induction treatment beginning on day 28. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy. CONSOLIDATION: Patients receive cytarabine IV continuously on days 1-3 and idarubicin IV over 15 minutes on days 1-2. TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or consolidation therapy.

Procedure: Allogeneic Hematopoietic Stem Cell TransplantationDrug: CytarabineDrug: IdarubicinOther: Laboratory Biomarker Analysis

Arm III (vorinostat, high-dose cytarabine, idarubicin)

EXPERIMENTAL

INDUCTION/RE-INDUCTIONI: Patients receive vorinostat PO TID on days 1-3, high-dose cytarabine IV continuously on days 4-7, and idarubicin IV over 15 minutes on days 4-6. Patients with residual blasts may receive re-induction treatment beginning on day 28. Patients achieving CR or CRi may proceed to allogeneic HSCT or to consolidation therapy. CONSOLIDATION: Patients receive vorinostat PO TID on days 1-3, cytarabine IV continuously on days 4-6, and idarubicin IV over 15 minutes on days 4-5. TRANSPLANT: Patients may undergo an allogeneic transplant after induction therapy or consolidation therapy. (Permanently closed to accrual, effective 6/2/2015) Patients previously randomized to Arm III may continue treatment with or without vorinostat.

Procedure: Allogeneic Hematopoietic Stem Cell TransplantationDrug: CytarabineDrug: IdarubicinOther: Laboratory Biomarker AnalysisDrug: Vorinostat

Interventions

Allogeneic Hematopoietic Stem Cell TransplantationPROCEDURE

Undergo allogeneic transplant

Also known as: Allogeneic Hematopoietic Cell Transplantation, allogeneic stem cell transplantation, HSC, HSCT

Arm I (standard dose cytarabine, daunorubicin hydrochloride)Arm II (high-dose cytarabine, idarubicin)Arm III (vorinostat, high-dose cytarabine, idarubicin)

CytarabineDRUG

Given IV

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosar-U, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Arm I (standard dose cytarabine, daunorubicin hydrochloride)Arm II (high-dose cytarabine, idarubicin)Arm III (vorinostat, high-dose cytarabine, idarubicin)

Daunorubicin HydrochlorideDRUG

Given IV

Also known as: Cerubidin, Cerubidine, Cloridrato de Daunorubicina, Daunoblastin, Daunoblastina, Daunoblastine, Daunomycin hydrochloride, Daunomycin, hydrochloride, Daunorubicin.HCl, Daunorubicini Hydrochloridum, FI-6339, Ondena, RP-13057, Rubidomycin Hydrochloride, Rubilem

Arm I (standard dose cytarabine, daunorubicin hydrochloride)

IdarubicinDRUG

Given IV

Also known as: 4-Demethoxydaunomycin, 4-demethoxydaunorubicin, 4-DMDR

Arm II (high-dose cytarabine, idarubicin)Arm III (vorinostat, high-dose cytarabine, idarubicin)

Laboratory Biomarker AnalysisOTHER

Correlative studies

Arm I (standard dose cytarabine, daunorubicin hydrochloride)Arm II (high-dose cytarabine, idarubicin)Arm III (vorinostat, high-dose cytarabine, idarubicin)

VorinostatDRUG

Given PO

Also known as: L-001079038, MSK-390, SAHA, Suberanilohydroxamic Acid, Suberoylanilide Hydroxamic Acid, Zolinza

Arm III (vorinostat, high-dose cytarabine, idarubicin)

Eligibility Criteria

Age18 Years - 60 Years

Sexall

Healthy VolunteersNo

Age GroupsAdult (18-64)

You may qualify if:

STEP 1 - INDUCTION/RE-INDUCTION
Patients must have morphologically confirmed newly diagnosed acute myelogenous leukemia (AML) with blood or bone marrow disease; patients with only extramedullary disease in the absence of bone marrow or blood involvement are not eligible; note: this protocol uses World Health Organization (WHO) diagnostic criteria for AML; patients with acute promyelocytic leukemia (APL, French-American-British \[FAB\], M3) or blastic transformation of chronic myelogenous leukemia (CML) are not eligible; patients with known core binding factor (CBF) or fms-like tyrosine kinase 3 (FLT3) related leukemias are eligible for this study, but should preferentially be placed on National Cancer Institute (NCI)-sponsored protocols specific for these subtypes, if available
Patients must have diagnostic/pre-treatment specimens obtained within 28 days prior to registration submitted for cytogenetic (and fluorescent in situ hybridization \[FISH\] if possible) analysis to determine risk status; high risk classification will be defined as del(5q)/-5, del(7q)/-7, abn3q26 \[inv(3)/t(3;3)\], 11q23 rearrangement \[except t(9;11)\], 17p-, t(6;9), t(9;22), complex (at least 3 unrelated abnormalities \[abn\]), and monosomal karyotype (either loss of two different chromosomes or loss of one chromosome along with a structural chromosome abnormality other than add, ring and mar); karyograms and cytogenetics/FISH analysis reports must be submitted for discipline review
Patients must be chemo-naïve, i.e., not have received any prior induction chemotherapy for AML or myelodysplastic syndrome (MDS); temporary prior measures such as apheresis or hydroxyurea are allowed; prior anthracycline therapy is allowed, but must not exceed a dose of 200 mg/m\^2 daunorubicin or equivalent; prior all-trans retinoic acid (ATRA) for suspected APL is allowed; prior methotrexate for central nervous system (CNS) involvement is allowed; patients with prior history of MDS must not have received azacitidine, decitabine, lenalidomide or vorinostat
Patients must have peripheral blood and bone marrow aspirate specimens obtained within 28 days prior to registration submitted for translational medicine; with patient consent, residuals will be banked for future research
Patients must have Zubrod performance status =\< 3
Patients must have either echocardiogram (ECHO) or multi gated acquisition scan (MUGA) with ejection fraction \>= 45% within 28 days prior to registration
Patients must not have prolonged corrected QT (QTc) interval (\> 500 msec) determined by electrocardiogram (EKG) within 28 days prior to registration
Patients must not have cardiac disease defined as: New York Heart Association (NYHA) \> class II; patients must not have unstable angina (angina symptoms at rest) or new onset angina (began within the last 3 months) or myocardial infarction within the past 6 months
Patients must not have any coexisting medical condition that is likely to interfere with study procedures or results, and must be reasonable candidates for intensive chemotherapy, in the opinion of their treating physicians
Patients who are known to be human immunodeficiency virus (HIV) positive (+) are eligible providing they meet all of the following additional criteria within 28 days prior to registration:
Cluster of differentiation (CD) 4 cells \>= 500/mm\^3
Viral load \< 50 copies of HIV messenger ribonucleic acid (mRNA)/mm\^3 if on combination antiretroviral therapy (cART) or \< 25,000 copies of HIV mRNA if not on cART
No zidovudine or stavudine as part of cART; patients who are HIV+ and do not meet all of these criteria are not eligible for this study
Patients with known hepatitis B or hepatitis C infection may be eligible providing they have viral load \< 800,000 IU/mL within 28 days prior to registration
+12 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

National Cancer Institute (NCI)lead

Study Sites (447)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Anchorage Radiation Therapy Center

Anchorage, Alaska, 99504, United States

Location

Alaska Breast Care and Surgery LLC