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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-001657-41 | EudraCT Number | ||
| 2023-507154-32-00 | Other Identifier | EU CT |
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| Name | Class |
|---|---|
| Genentech, Inc. | INDUSTRY |
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This is a Phase 1b, open-label, non-randomized, multicenter, dose-finding study evaluating venetoclax in combination with azacitidine in participants with treatment-naïve higher-risk MDS comprising a dose-escalation portion and a safety expansion portion.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Venetoclax + Azacitidine | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Azacitidine | Drug | Powder for injection; taken subcutaneously (SC) or intravenous (IV); Administered on Days 1-7 of 28 days cycle or Days 1-5 of Week 1 & Days 1-2 of Week 2 of 28 day cycle. |
| Measure | Description | Time Frame |
|---|---|---|
| AUCt for Azacitidine | Area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) for azacitidine. | Up to 32 days |
| Cmax of venetoclax | Maximum plasma concentration (Cmax) of venetoclax. | Up to 32 days |
| AUCt for venetoclax | Area under the plasma concentration-time curve (AUC) from 0 to the time of the last measurable concentration (AUCt) for venetoclax. | Up to 32 days |
| Tmax of venetoclax | Time to Cmax (peak time, Tmax) of venetoclax. | Up to 32 days |
| AUC[0 to infinity] for azacitidine | Area under the plasma concentration-time curve from Time 0 to infinite time. | Up to 32 days |
| Recommended Phase 2 dose (RPTD) and dosing schedule of venetoclax in combination with azacitidine | The RPTD of venetoclax [co-administered venetoclax and azacitidine] will be determined during the dose escalation phase of the study. RPTD will be determined using available safety and pharmacokinetics data [upon completion of the dose escalation phase]. | Measured from Day 1 until Day 28 per dose level. |
| Half-life (t[1/2]) for azacitidine | Terminal elimination half-life (t[1/2]) for azacitidine. | Up to 32 days |
| Measure | Description | Time Frame |
|---|---|---|
| Rate of red blood cell (RBC) transfusion independence | Percentages of participants who become RBC transfusion-independent. | Measured from Cycle 1 Day 1 as long as the participant continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months. |
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Inclusion Criteria:
Participant must have documented diagnosis of untreated de novo MDS with:
Eastern Cooperative Oncology Group (ECOG) performance score of less than or equal to 2.
Exclusion Criteria:
Participant has received prior therapy for MDS. (Prior supportive care in form of transfusions or growth factors, etc., is not considered prior therapy).
Participant has received prior therapy with a BCL-2 Homology 3 (BH3) mimetic.
Participant has a diagnosis other than previously untreated de novo MDS (as defined in the protocol) including:
Participant has received allogeneic Hematopoietic Stem Cell Transplantation (HSCT) or solid organ transplantation.
Participant has received a live attenuated vaccine within 4 weeks prior to the first dose of study drug.
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| Name | Affiliation | Role |
|---|---|---|
| ABBVIE INC. | AbbVie | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Duplicate_University of Arizona Cancer Center - North Campus /ID# 154155 | Tucson | Arizona | 85719-1478 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39652823 | Derived | Garcia JS, Platzbecker U, Odenike O, Fleming S, Fong CY, Borate U, Jacoby MA, Nowak D, Baer MR, Peterlin P, Chyla B, Wang H, Ku G, Hoffman D, Potluri J, Garcia-Manero G. Efficacy and safety of venetoclax plus azacitidine for patients with treatment-naive high-risk myelodysplastic syndromes. Blood. 2025 Mar 13;145(11):1126-1135. doi: 10.1182/blood.2024025464. |
| Label | URL |
|---|---|
| This clinical study may be evaluating a usage that is not currently FDA approved. Please see US Prescribing Information for approved uses. | View source |
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| Venetoclax | Drug | Oral; Tablet |
|
|
| Cmax for azacitidine | Maximum plasma concentration (Cmax) of azacitidine. | Up to 32 days |
| AUC[0-24] for venetoclax | AUC over a 24-hour dose interval (AUC[0-24]) for venetoclax. | Up to 32 days |
| Clearance (CL) for azacitidine | Clearance is defined as the volume of plasma cleared of the drug per unit time. | Up to 32 days |
| Tmax for azacitidine | Time to Cmax (peak time, Tmax) of azacitidine. | Up to 32 days |
| Complete Remission (CR) Rate | Complete remission rate will be defined as the proportion of participants who achieved a complete response per the International Working Group (IWG) 2006 criteria for Myelodysplastic Syndromes (MDS). | Measured from Cycle 1 Day 1 as long as the participant continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months. |
| Progression-Free Survival (PFS) | PFS is defined as the number of days from the date of the first dose of study drug to the date of earliest disease progression or death due to disease progression or febrile neutropenia. | Measured from the date of first dose of study drug to the date of earliest disease progression or death due to disease progression or febrile neutropenia, and for an anticipated maximum duration of 24 months. |
| Overall Survival (OS) | OS is defined as number of days from the date of first dose of the study drug to the date of death of any cause. | Measured from the date of first dose of study drug to the date of death, and for up to 5 years after the last participant is enrolled. |
| Hematologic Improvement (HI) rate | Percentages of participants with HI (erythroid/platelet/neutrophil responses). | Measured from Cycle 1 Day 1 as long as the participant continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months. |
| Rate of platelet (PLT) transfusion independence | Percentages of participants who become platelet transfusion-independent. | Measured from Cycle 1 Day 1 as long as the participant continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months. |
| Event-Free Survival (EFS) | Event-free survival (EFS) will be defined as the number of days from the date of the first dose of study drug to the date of earliest disease progression or death of any cause. | Measured from the date of the first dose of study drug to the date of earliest disease progression, death of any cause and for up to 5 yrs after the last participant is enrolled |
| Time to transformation to acute myeloid leukemia (AML) | Defined as the number of days from the date of the first dose of study drug to the date of documented AML transformation. | Measured from the date of first dose of study drug to date of documented AML transformation, defined as the presence of blast count greater than or equal to 20% in either peripheral blood or bone marrow for an anticipated maximum duration of 24 months. |
| Overall Response Rate (OR) | OR (equals the rates of complete remission [CR] + partial remission [PR]) of venetoclax in combination with azacitidine. | Measured from Cycle 1 Day 1 as long as the participant continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent and for an anticipated maximum duration of 24 months. |
| Time to next treatment (TTNT) | Time to next treatment (TTNT) will be defined as the time from the first dose of study drug to start of new non-protocol specified MDS therapy or death from any cause. | Measured from the first dose of study drug to start of new non-protocol specified MDS therapy, and for up to 5 years after the last participant is enrolled. |
| Marrow Complete Remission (mCR) Rate | Defined as the proportion of participants who achieved a marrow complete response with or without hematological improvement per the International Working Group (IWG) 2006 criteria for Myelodysplastic Syndromes. | Measured from Cycle 1 Day 1 as long as the participant continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months. |
| Modified Overall Response Rate (mOR) | mOR (equals CR + PR + mCR) of venetoclax in combination with azacitidine. | Measured from Cycle 1 Day 1 as long as the participant continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent and for an anticipated maximum duration of 24 months. |
| Duration of CR | Duration of CR will be defined as the number of days from the date of first response CR to the earliest documentation of progressive disease or death of any cause, whichever occurs earlier. | Measured from Cycle 1 Day 1 as long as the participant continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months. |
| Duration of mOR | Duration of response (mOR) will be defined as the number of days from the date of first response (CR, PR or mCR) to the earliest documentation of progressive disease or death of any cause, whichever occurs earlier. | Measured from Cycle 1 Day 1 as long as the participant continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent and for an anticipated maximum duration of 24 months. |
| Duration of OR | Duration of response (OR) will be defined as the number of days from the date of first response (CR or PR) to the earliest documentation of progressive disease or death of any cause, whichever occurs earlier. | Measured from Cycle 1 Day 1 as long as the participant continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent and for an anticipated maximum duration of 24 months. |
| Rate of AML transformation | The AML transformation rate is defined as the proportion of participants transformed to Acute Myelogenous Leukemia. | Measured from the date of first dose of study drug to date of documented AML transformation, defined as the presence of blast count greater than or equal to 20% in either peripheral blood or bone marrow for an anticipated maximum duration of 24 months. |
| Time to First Response (CR) | Time to first response (CR) will be defined as the number of days from the date of first dose of the study drug to the date of the first response of CR. | Measured from Cycle 1 Day 1 as long as the participant continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent, and for an anticipated maximum duration of 24 months. |
| Time to First Response (mOR) | Time to first response (mOR) will be defined as the number of days from the date of first dose of the study drug to the date of the first response of (CR, PR, or mCR). | Measured from Cycle 1 Day 1 as long as the participant continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent and for an anticipated maximum duration of 24 months. |
| Time to First Response (OR) | Time to first response (OR) will be defined as the number of days from the date of first dose of the study drug to the date of the first response of (CR or PR). | Measured from Cycle 1 Day 1 as long as the participant continues to benefit, or until the occurrence of unacceptable toxicity, death, exercise of investigator discretion, or withdrawal of consent and for an anticipated maximum duration of 24 months. |
| The University of Chicago Medical Center /ID# 153673 |
| Chicago |
| Illinois |
| 60637-1443 |
| United States |
| University of Maryland, Baltimore /ID# 153669 | Baltimore | Maryland | 21201 | United States |
| Tufts Medical Center /ID# 153672 | Boston | Massachusetts | 02111-1552 | United States |
| Dana-Farber Cancer Institute /ID# 152735 | Boston | Massachusetts | 02215 | United States |
| Washington University-School of Medicine /ID# 153671 | St Louis | Missouri | 63110 | United States |
| Columbia University Medical Center /ID# 153661 | New York | New York | 10032-3729 | United States |
| Weill Cornell Medical College /ID# 155524 | New York | New York | 10065 | United States |
| Oregon Medical Research Center /ID# 152734 | Portland | Oregon | 97239 | United States |
| University of Pittsburgh MC /ID# 153662 | Pittsburgh | Pennsylvania | 15260 | United States |
| Tennessee Oncology-Nashville Centennial /ID# 222769 | Nashville | Tennessee | 37203-1632 | United States |
| Vanderbilt University Medical Center /ID# 152738 | Nashville | Tennessee | 37232-0011 | United States |
| UT MD Anderson Cancer Center /ID# 153809 | Houston | Texas | 77030 | United States |
| Concord Repatriation General Hospital /ID# 154958 | Concord | New South Wales | 2139 | Australia |
| Duplicate_St. Vincent's Hospital, Darlinghurst /ID# 222846 | Darlinghurst | New South Wales | 2010 | Australia |
| St George Hospital /ID# 154954 | Kogarah | New South Wales | 2217 | Australia |
| Liverpool Hospital /ID# 222410 | Liverpool | New South Wales | 2170 | Australia |
| Calvary Mater Newcastle /ID# 154957 | Waratah | New South Wales | 2298 | Australia |
| Duplicate_Princess Alexandra Hospital /ID# 154990 | Woolloongabba | Queensland | 4102 | Australia |
| Austin Health /ID# 154955 | Heidelberg | Victoria | 3084 | Australia |
| The Alfred Hospital /ID# 154956 | Melbourne | Victoria | 3004 | Australia |
| Fiona Stanley Hospital /ID# 222847 | Murdoch | Western Australia | 6150 | Australia |
| Juravinski Cancer Centre /ID# 152947 | Hamilton | Ontario | L8V 1C3 | Canada |
| Centre Hospitalier Universitaire de Nantes, Hotel Dieu -HME /ID# 153828 | Nantes | Pays de la Loire Region | 44000 | France |
| Hôpital Saint-Louis /ID# 153827 | Paris | 75010 | France |
| Universitatsklinikum Mannheim /ID# 153140 | Mannheim | Baden-Wurttemberg | 68167 | Germany |
| Klinikum rechts der Isar /ID# 153139 | Munich | Bavaria | 81675 | Germany |
| Universitaetsklinikum Koeln /ID# 153141 | Cologne | North Rhine-Westphalia | 50937 | Germany |
| Duplicate_Universitaetsklinikum Carl Gus /ID# 153958 | Dresden | Saxony | 01307 | Germany |
| Universitaetsklinikum Leipzig /ID# 153142 | Leipzig | Saxony | 04103 | Germany |
| Universitaetsklinikum Halle (Saale) /ID# 153760 | Halle | 06120 | Germany |
| Duplicate_IRCCS AOU di Bologna - Policlinico Sant'Orsola-Malpighi /ID# 153763 | Bologna | Emilia-Romagna | 40138 | Italy |
| Duplicate_Azienda Ospedaliero-Universitaria Policlinico Umberto I /ID# 153764 | Rome | Roma | 00161 | Italy |
| Norfolk and Norwich University Hospitals NHS Foundation Trust /ID# 156492 | Norwich | Norfolk | NR4 7UY | United Kingdom |
| Oxford University Hospitals NHS Foundation Trust /ID# 222567 | Oxford | Oxfordshire | OX3 9DU | United Kingdom |
| University Hospitals Birmingham NHS Foundation Trust /ID# 158810 | Birmingham | B15 2TH | United Kingdom |
| King's College Hospital NHS Foundation Trust /ID# 156489 | London | SE5 9RS | United Kingdom |
| ID | Term |
|---|---|
| D009190 | Myelodysplastic Syndromes |
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D001374 | Azacitidine |
| C579720 | venetoclax |
| ID | Term |
|---|---|
| D001372 | Aza Compounds |
| D009930 | Organic Chemicals |
| D003562 | Cytidine |
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |
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