Acute Myeloid Leukemia Clinical Trial
Official title:
A Phase 3, Multicenter, Randomized, Open-Label Study of Guadecitabine (SGI-110) Versus Treatment Choice in Adults With Previously Treated Acute Myeloid Leukemia
Verified date | May 2023 |
Source | Astex Pharmaceuticals, Inc. |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Multicenter, randomized, open-label, parallel-group study of guadecitabine vs treatment choice (TC). Participants will be randomly assigned in a 1:1 ratio to either guadecitabine or TC. TC options include the 8 high or low intensity, locally available regimens below; or Best supportive Care (BSC) alone: - High intensity (intermediate or high dose cytarabine [HiDAC]; mitoxantrone, etoposide, and cytarabine [MEC]; or fludarabine, cytarabine, granulocyte colony stimulating factor [G-CSF], +/- idarubicin [FLAG/FLAG-Ida]). - Low intensity (low dose cytarabine [LDAC], decitabine, or azacitidine). - BSC.
Status | Completed |
Enrollment | 302 |
Est. completion date | June 1, 2020 |
Est. primary completion date | January 20, 2020 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. Adult participants =18 years of age who are able to understand study procedures, comply with them, and provide written informed consent before any study-specific procedure. 2. History of cytologically or histologically confirmed diagnosis of AML (except acute promyelocytic leukemia) according to the 2008 World Health Organization (WHO) classification (bone marrow [BM] or peripheral blood [PB] blast counts =20%). 3. Performance status (Eastern Cooperative Oncology Group; ECOG) of 0-2. 4. Participants with AML previously treated with initial induction therapy using a standard intensive chemotherapy regimen, including cytarabine and an anthracycline, and who are refractory to initial induction (primary refractory) or in relapse after such initial induction with or without prior HCT. 5. Participants must have either PB or BM blasts =5% at time of randomization. 6. Creatinine clearance or glomerular filtration rate =30 mL/min as estimated by the Cockroft-Gault (C-G) or other medically acceptable formulas, such as MDRD (Modification of Diet in Renal Disease) or CKD-EPI (the Chronic Kidney Disease Epidemiology Collaboration). 7. Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of child-bearing potential and men with female partners of child-bearing potential must agree to practice 2 highly effective contraceptive measures of birth control and must agree not to become pregnant or father a child (a) while receiving treatment of guadecitabine, decitabine, or azacitidine and for at least 3 months after completing treatment and (b) while receiving treatment with high-intensity TC or LDAC and for at least 6 months after completing treatment. Exclusion Criteria: 1. Known clinically active central nervous system (CNS) or extramedullary AML, except leukemia cutis. 2. Participants who are in first relapse after initial induction, if they had a response duration of >12 months from date when first response first documented or if they are good candidates for HCT. 3. BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis). 4. Second malignancy currently requiring active therapy, except breast or prostate cancer stable on or responding to endocrine therapy. 5. Grade 3 or higher Graft Versus Host Disease (GVHD), or GVHD on either a calcineurin inhibitor or prednisone more than 5 mg/day. 6. Prior treatment with guadecitabine for any indication, or more than 2 cycles of prior decitabine or azacitidine. 7. Hypersensitivity to decitabine, guadecitabine, or any of their excipients. 8. Treated with any investigational therapy within 2 weeks of the first dose of study treatment. 9. Total serum bilirubin >2.5 × upper limit of normal (ULN; except for participants with Gilbert's Syndrome for whom direct bilirubin is <2.5 × ULN), or liver cirrhosis, or chronic liver disease Child-Pugh Class B or C. 10. Known active human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Inactive hepatitis carrier status or low viral hepatitis titer on antivirals is allowed. 11. Known significant mental illness or other condition such as active alcohol or other substance abuse or addiction that, in the opinion of the investigator, predisposes the participant to high risk of noncompliance with the protocol. 12. Refractory congestive heart failure unresponsive to medical treatment; active infection resistant to all antibiotics; or non-AML-associated pulmonary disease requiring >2 liters per minute (LPM) oxygen, or any other condition that puts the participant at an imminent risk of death. 13. Participants with high PB blasts >50% AND poor ECOG PS of 2. |
Country | Name | City | State |
---|---|---|---|
Belgium | AZ Sint-Jan Brugge-Oostende AV | Brugge | |
Belgium | Cliniques Universitaires Saint-Luc | Brussels | |
Belgium | Universitair Ziekenhuis Gent | Gent | |
Canada | Tom Baker Cancer Centre | Calgary | Alberta |
Canada | University of Alberta Hospital | Edmonton | Alberta |
Canada | Hopital Maisonneuve Rosemont | Montreal | |
Canada | McGill University Health Centre | Montreal | Quebec |
Canada | Princess Margaret Cancer Centre | Toronto | Ontario |
Denmark | Aarhus University Hospital | Aarhus C | |
Denmark | Rigshospitalet | Copenhagen | |
France | Centre Hospitalier de la Côte Basque | Bayonne | |
France | Hôpital de la Conception | Marseille | |
France | CHRU Montpellier - Saint Eloi | Montpellier | |
France | Groupe Hospitalier de la Région de Mulhouse et Sud Alsace | Mulhouse | |
France | Hôpital Saint-Louis | Paris | |
France | CHU Hopitaux de Bordeaux - Hôpital Haut-Lévêque | Pessac | |
France | Centre Hospitalier Lyon-Sud | Pierre Bénite | |
France | Centre Henri Becquerel | Rouen cedex 1 | |
France | Institut Universitaire du Cancer de Toulouse - Oncopole | Toulouse | |
Germany | Städtisches Klinikum Braunschweig gGmbH | Braunschweig | |
Germany | Marien Hospital Düsseldorf GmbH | Düsseldorf | |
Germany | Universitätsklinikum Halle (Saale) | Halle | |
Germany | Universitätsklinikum Schleswig-Holstein | Kiel | |
Germany | Universitätsklinikum Leipzig | Leipzig | Sachsen |
Germany | Medizinischen Fakultät Mannheim der Universität Heidelberg | Mannheim | |
Germany | Klinikum der Universität München | Muenchen | |
Germany | Universitätsklinikum Ulm | Ulm | |
Hungary | SE ÁOK I. sz. Belgyógyászati Klinika | Budapest | |
Hungary | Debreceni Egyetem Klinikai Központ | Debrecen | |
Hungary | Somogy Megyei Kaposi Mór Oktató Kórház | Kaposvar | |
Hungary | Pecsi Tudomanyegyetem Klinikai Központ | Pécs | |
Hungary | Szegedi Tudományegyetem | Szeged | |
Italy | IRCCS AOU San Martino - IST | Genova | |
Italy | Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico | Milano | |
Italy | Ospedale San Raffaele - Milano | Milano | |
Italy | A.O.R.N. "A. Cardarelli" | Napoli | |
Italy | A.S.U Integrata di Udine - Presidio Ospedaliero Santa Maria della Misericordia | Udine | |
Japan | Akita University Hospital | Akita-shi | |
Japan | Chugoku Central Hospital | Fukuyama-Shi | |
Japan | Tokai University Hospital | Isehara-shi | |
Japan | Saitama Medical Center | Kawagoe-Shi | |
Japan | Kobe City Medical Center General Hospital | Kobe-shi | |
Japan | Japanese Red Cross Kyoto Daini Hospital | Kyoto-shi | |
Japan | University Hospital, Kyoto Prefectural University of Medicine | Kyoto-shi | |
Japan | Gunmaken Saiseikai Maebashi Hospital | Maebashi-shi | |
Japan | Nagasaki University Hospital | Nagasaki-shi | |
Japan | The Japanese Red Cross Nagasaki Genbaku Hospital | Nagasaki-Shi | |
Japan | Kindai University Hospital | Osakasayama-Shi | |
Japan | Saga University Hospital | Saga-shi | |
Japan | NTT Medical Center Tokyo | Shinagawa-Ku | |
Japan | Shizuoka Cancer Center | Shizuoka | |
Japan | National Hospital Organization Disaster Medical Center | Tachikawa-Shi | |
Japan | Yamagata University Hospital | Yamagata-Shi | |
Japan | University of Fukui Hospital | Yoshida-Gun | |
Korea, Republic of | Pusan National University Hospital | Busan | |
Korea, Republic of | Asan Medical Center | Seoul | |
Korea, Republic of | Samsung Medical Center | Seoul | |
Korea, Republic of | Seoul National University Hospital | Seoul | |
Korea, Republic of | Severance Hospital | Seoul | |
Korea, Republic of | The Catholic University of Korea, Seoul St. Mary's Hospital | Seoul | |
Korea, Republic of | Ulsan University Hospital (UUH) | Ulsan | |
Poland | Instytut Hematologii i Transfuzjologi | Warszawa | |
Spain | Hospital Clínic de Barcelona | Barcelona | |
Spain | Hospital de la Santa Creu i Sant Pau | Barcelona | |
Spain | Hospital Duran i Reynals | Barcelona | |
Spain | Vall d'Hebron Institut d'Oncologia | Barcelona | |
Spain | Hospital San Pedro de Alcántara | Cáceres | |
Spain | Hospital Universitario Reina Sofía | Córdoba | |
Spain | Hospital General Universitario Gregorio Marañón | Madrid | |
Spain | Hospital Universitario Central de Asturias | Oviedo | |
Spain | Hospital Universitario Virgen del Rocío | Sevilla | |
Spain | Hospital Universitari i Politècnic La Fe | Valencia | |
Spain | Hospital Universitario Dr. Peset | Valencia | |
Sweden | Sahlgrenska University Hospital | Göteborg | |
Ukraine | Khmelnytskyi Regional Hospital | Khmelnytskyi | |
Ukraine | Poltava Regional Clinical Hospital named after M. V. Sklifosovskoho | Poltava | |
United Kingdom | Heart of England NHS Foundation Trust - Heartlands Hospital | Birmingham | |
United Kingdom | University Hospitals Bristol NHS Foundation Trust - Bristol Haematology and Oncology Centre | Bristol | |
United Kingdom | East Kent Hospitals University NHS Foundation Trust - Kent and Canterbury Hospital | Canterbury | |
United Kingdom | St. James's University Hospital | Leeds | |
United States | University of New Mexico School of Medicine | Albuquerque | New Mexico |
United States | Roswell Park Cancer Institute | Buffalo | New York |
United States | The University of Chicago Medical Center | Chicago | Illinois |
United States | Baylor Research Institute | Dallas | Texas |
United States | Duke Cancer Institute | Durham | North Carolina |
United States | John Theurer Cancer Center at Hackensack University Medical Center | Hackensack | New Jersey |
United States | MD Anderson Cancer Center | Houston | Texas |
United States | Franciscan Research Center | Indianapolis | Indiana |
United States | University of Southern California | Los Angeles | California |
United States | West Virginia University Hospitals, Inc. | Morgantown | West Virginia |
United States | Vanderbilt University Medical Center | Nashville | Tennessee |
United States | Weill Cornell Medical College | New York | New York |
United States | University of Oklahoma Medical Center | Oklahoma City | Oklahoma |
United States | Hospital of the University of Pennsylvania | Philadelphia | Pennsylvania |
United States | Temple University Hospital | Philadelphia | Pennsylvania |
Lead Sponsor | Collaborator |
---|---|
Astex Pharmaceuticals, Inc. |
United States, Belgium, Canada, Denmark, France, Germany, Hungary, Italy, Japan, Korea, Republic of, Poland, Spain, Sweden, Ukraine, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Overall Survival | Overall survival is defined as number of days from day of randomization to date of death, regardless of cause. | From the date of randomization until the date of death, or approximately 34 months | |
Secondary | Event-Free Survival | Event-free survival is defined as number of days from randomization to earliest date of treatment discontinuation (for reasons other than initiation of hematopoietic cell transplant [HCT]), start of alternative anti-leukemia therapy (except HCT), or death. | From the date of randomization until the date of death, or approximately 38 months | |
Secondary | Long-Term Survival | Survival rate at 1 year after randomization; participants were also followed to estimate 2-year survival rate. | Up to approximately 38 months | |
Secondary | Number of Days Alive and Out of the Hospital (NDAOH) | Number of days participants alive and out of hospital during first 6 months of the study. | 6 months | |
Secondary | Transfusion Independence Rate | Number of participants without red blood cells (RBC) or platelet transfusion for any 8-week period after treatment divided by total number of participants in efficacy analysis. | Baseline up to approximately 38 months | |
Secondary | Complete Response Rate | The Complete response (CR) rate based on modified International Working Group (IWG) 2003 AML Response Criteria was calculated as the number of participants with a best response of CR divided by the total number of participants included in the efficacy analysis. CR as per modified 2003 IWG AML Response Criteria is absolute neutrophil count (ANC) =1000/µL, platelets =100,000/µL, independence from red blood cells (RBC) and platelet transfusions over the past week, no leukemic blasts in peripheral blood and bone marrow should contain less than 5% blast cells. | Baseline to end of treatment, or approximately 38 months | |
Secondary | Combined Complete Response and Complete Response With Partial Hematologic Recovery Rate | The combined CR and CR with partial hematologic recovery rate based on modified International Working Group (IWG) 2003 AML Response Criteria was calculated as number of participants with CR and CR with partial hematologic recovery divided by the total number of participants included in the efficacy analysis. CR as per modified 2003 IWG AML Response Criteria is absolute neutrophil count (ANC) =1000/µL, platelets =100,000/µL, independence from red blood cells (RBC) and platelet transfusions over the past week, no leukemic blasts in peripheral blood and bone marrow should contain less than 5% blast cells. | Baseline to end of treatment, or approximately 38 months | |
Secondary | Composite Complete Response Rate | Composite complete response rate based on modified IWG 2003 AML Response Criteria defined as number of participants with best response of CR, CR with incomplete platelet recovery (CRp), or CR with incomplete blood count recovery (CRi) divided by total number of participants in efficacy analysis. CR as per modified 2003 IWG AML Response Criteria is ANC =1000/µL, platelets =100,000/µL, independence from RBC and platelet transfusions over the past week, no leukemic blasts in peripheral blood and bone marrow should contain less than 5% blast cells. CRp is defined as ANC =1000/µL, Platelets <100,000/µL, independence from RBC transfusions over the past week, no leukemic blasts and bone marrow should contain less than 5% blast cells. CRi is defined as ANC <1000/µL, no leukemic blasts and bone marrow should contain less than 5% blast cells. | Baseline to end of treatment, or approximately 38 months | |
Secondary | Hematopoietic Cell Transplant (HCT) Rate | Number of participants who received HCT after randomization divided by total number of participants in efficacy analysis. | Baseline to long term follow-up or approximately 38 months | |
Secondary | Duration of Complete Response (CR) + CR With Partial Hematologic Recovery (CRh) | The time from first CR or CRh to time of relapse (the date of the earliest of the following 3 events):
relapse (defined as the earliest time point whereby BM assessment or PB assessment by the investigator indicate relapse/disease progression due to confirmed reappearance of leukemic blasts in PB or =5% leukemic blasts in BM, or clinical progression determined by the investigator), start of alternative therapy (except HCT) or death. |
Baseline to end of treatment, or approximately 38 months | |
Secondary | Change From Baseline in EuroQoL-5 Dimension 5 Level (EQ-5D-5L) Index Scores | Index score is calculated based on 5-level version of the EQ-5D descriptive system using the value set for England.
The range of index score is from -0.281 (for the worst health state, score of 5 for all categories) to 1 (for the best health state, score of 1 for all categories). |
Baseline to 6 months | |
Secondary | Change in EQ-5D-5L Visual Analogue Scale (VAS) Score | VAS score is obtained using vertical 20-cm visual analogue scale with the top value of 100 labelled as 'the best health you can imagine' and the bottom value of 0 labelled as 'the worst health you can imagine'. | Baseline to 6 months | |
Secondary | Percentage of Participants With Adverse Events (AEs) | An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including a clinically significant abnormal finding in laboratory tests or other diagnostic procedures), symptom, or disease temporally associated with the use of a drug, without any judgment about causality. | From first dose until 30 days after the last dose of study drug, or approximately 38 months | |
Secondary | All-Cause Mortality | All-cause mortality in the first 30 days and first 60 days after the start of treatment divided by the total number of participants receiving at least one dose of study treatment. | From the first dose until 60 days after the first dose of study drug |
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT05400122 -
Natural Killer (NK) Cells in Combination With Interleukin-2 (IL-2) and Transforming Growth Factor Beta (TGFbeta) Receptor I Inhibitor Vactosertib in Cancer
|
Phase 1 | |
Recruiting |
NCT04460235 -
Immunogenicity of an Anti-pneumococcal Combined Vaccination in Acute Leukemia or Lymphoma
|
Phase 4 | |
Completed |
NCT03678493 -
A Study of FMT in Patients With AML Allo HSCT in Recipients
|
Phase 2 | |
Completed |
NCT04022785 -
PLX51107 and Azacitidine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
|
Phase 1 | |
Recruiting |
NCT05424562 -
A Study to Assess Change in Disease State in Adult Participants With Acute Myeloid Leukemia (AML) Ineligible for Intensive Chemotherapy Receiving Oral Venetoclax Tablets in Canada
|
||
Terminated |
NCT03224819 -
Study of Emerfetamab (AMG 673) in Adults With Relapsed/Refractory Acute Myeloid Leukemia (AML)
|
Early Phase 1 | |
Completed |
NCT03197714 -
Clinical Trial of OPB-111077 in Patients With Relapsed or Refractory Acute Myeloid Leukaemia
|
Phase 1 | |
Active, not recruiting |
NCT03844048 -
An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial
|
Phase 3 | |
Active, not recruiting |
NCT04070768 -
Study of the Safety and Efficacy of Gemtuzumab Ozogamicin (GO) and Venetoclax in Patients With Relapsed or Refractory CD33+ Acute Myeloid Leukemia:Big Ten Cancer Research Consortium BTCRC-AML17-113
|
Phase 1 | |
Active, not recruiting |
NCT04107727 -
Trial to Compare Efficacy and Safety of Chemotherapy/Quizartinib vs Chemotherapy/Placebo in Adults FMS-like Tyrosine Kinase 3 (FLT3) Wild-type Acute Myeloid Leukemia (AML)
|
Phase 2 | |
Recruiting |
NCT04385290 -
Combination of Midostaurin and Gemtuzumab Ozogamicin in First-line Standard Therapy for Acute Myeloid Leukemia (MOSAIC)
|
Phase 1/Phase 2 | |
Recruiting |
NCT04920500 -
Bioequivalence of Daunorubicin Cytarabine Liposomes in Naive AML Patients
|
N/A | |
Recruiting |
NCT03897127 -
Study of Standard Intensive Chemotherapy Versus Intensive Chemotherapy With CPX-351 in Adult Patients With Newly Diagnosed AML and Intermediate- or Adverse Genetics
|
Phase 3 | |
Active, not recruiting |
NCT04021368 -
RVU120 in Patients With Acute Myeloid Leukemia or High-risk Myelodysplastic Syndrome
|
Phase 1 | |
Recruiting |
NCT03665480 -
The Effect of G-CSF on MRD After Induction Therapy in Newly Diagnosed AML
|
Phase 2/Phase 3 | |
Completed |
NCT02485535 -
Selinexor in Treating Patients With Intermediate- and High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome After Transplant
|
Phase 1 | |
Enrolling by invitation |
NCT04093570 -
A Study for Participants Who Participated in Prior Clinical Studies of ASTX727 (Standard Dose), With a Food Effect Substudy at Select Study Centers
|
Phase 2 | |
Recruiting |
NCT04069208 -
IA14 Induction in Young Acute Myeloid Leukemia
|
Phase 2 | |
Recruiting |
NCT05744739 -
Tomivosertib in Relapsed or Refractory Acute Myeloid Leukemia (AML)
|
Phase 1 | |
Recruiting |
NCT04969601 -
Anti-Covid-19 Vaccine in Children With Acute Leukemia and Their Siblings
|
Phase 1/Phase 2 |