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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-001904-46 | EudraCT Number |
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| Name | Class |
|---|---|
| Celgene; Genentech, Inc. | UNKNOWN |
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This is a Phase 1b, open-label, multicenter study designed to evaluate the safety and pharmacokinetics of venetoclax as a single-agent and in combination with azacitidine in participants with relapsed/refractory Myelodysplastic Syndromes (MDS).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Venetoclax monotherapy (Cohort 1) | Experimental |
| |
| Venetoclax + azacitidine (Cohort 2) | Experimental |
| |
| Safety Expansion (Cohort 3) | Experimental |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| venetoclax | Drug | Tablet |
|
| 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 |
| Clearance (CL) for azacitidine | Up to 32 days | |
| Cmax for azacitidine | Maximum plasma concentration (Cmax) of azacitidine | Up to 32 days |
| Tmax for venetoclax | Time to Cmax (peak time, Tmax) for venetoclax | Up to 32 days |
| Recommended Phase 2 Dose (RPTD) and dosing schedules of venetoclax as monotherapy and in combination with azacitidine | Measured from Day 1 until day 28 per dose level. | |
| AUC[0 to infinity] for azacitidine | Area under the plasma concentration-time curve from Time 0 to infinite time. | Up to 32 days |
| Tmax for azacitidine | Time to Cmax (peak time, Tmax) for 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 |
| AUCt for venetoclax |
| Measure | Description | Time Frame |
|---|---|---|
| Event-Free Survival (EFS) | Measured from the date of the first dose of study drug to date of earliest disease progression, death, or initiation of new non-protocol-specified anti-MDS therapy without documented progression, and for up to 5 years after the last subject is enrolled. | |
| Overall Survival (OS) |
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Inclusion Criteria:
Subjects who have relapsed or refractory MDS.
Subject enrolled in venetoclax monotherapy must have documented failure of prior therapy with a hypomethylating agent (HMA). HMA-failure is defined as:
Subjects must have presence of < 20% bone marrow blasts per bone marrow biopsy/aspirate at screening.
Subject is not a candidate to undergo allogenic hematopoietic stem cell transplantation (HSCT).
Subject must have an Eastern Cooperative Oncology Group (ECOG) performance score of ≤2.
Subject must have adequate hematologic, renal, and hepatic function.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| ABBVIE INC. | AbbVie | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Arizona Cancer Center - North Campus /ID# 157503 | Tucson | Arizona | 85719-1478 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36309981 | Derived | Zeidan AM, Borate U, Pollyea DA, Brunner AM, Roncolato F, Garcia JS, Filshie R, Odenike O, Watson AM, Krishnadasan R, Bajel A, Naqvi K, Zha J, Cheng WH, Zhou Y, Hoffman D, Harb JG, Potluri J, Garcia-Manero G. A phase 1b study of venetoclax and azacitidine combination in patients with relapsed or refractory myelodysplastic syndromes. Am J Hematol. 2023 Feb;98(2):272-281. doi: 10.1002/ajh.26771. Epub 2022 Nov 10. | |
| 33191169 |
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| azacitidine | Drug | Powder for injection, subcutaneously or intravenous |
|
|
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 |
| Cmax of venetoclax | Maximum plasma concentration (Cmax) of venetoclax | Up to 32 days |
| Half-life (t[1/2]) for azacitidine | Terminal elimination half-life (t[1/2]) for azacitidine | Up to 32 days |
| Number of Participants With Adverse Events (AEs) | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the participant and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent adverse events/treatment-emergent serious adverse events (TEAEs/TESAEs) are defined as any event that began or worsened in severity on or after the first dose of study drug. | Up to Maximum of 24 months |
| Measured from the date of first dose of study drug to the date of death, and for up to 5 years after the last subject is enrolled. |
| Rate of Modified Overall Response (mORR) | Proportion of participants with a mORR using best outcome will be calculated. | Measured from Cycle 1 Day 1 (C1D1) as long as the subject 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) | Measured from first dose of study drug to start of new non-protocol specified MDS therapy, and for up to 5 years after the last subject is enrolled. |
| Duration of mORR | Defined as the number of days from the date of first response (CR, mCR or PR) to the earliest documentation of progressive disease or death of any cause, whichever occurs earlier.. | Measured from the date of first response (CR, mCR or PR) to the earliest documentation of progressive disease (PD), and for an anticipated maximum duration of 24 months. |
| Rate of platelet (PLT) transfusion independence | Proportion of participants who become platelet transfusion-independent | Measured from Cycle 1 Day 1 as long as the subject 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 Transformation acute myeloid leukemia (AML) | Defined as blast count greater than or equal to 20% in either peripheral blood or bone marrow. | Measured from the date of first dose of study drug to the date of documented AML transformation for an anticipated maximum duration of 24 months. |
| Progression-Free Survival (PFS) | Measured from the date of the first dose of study drug to the date of earliest disease progression or death, and for an anticipated maximum duration of 24 months. |
| Overall Response Rate (ORR) | ORR (equals the sum of rates of complete remission [CR] + marrow complete remission (mCR) + partial remission [PR]) of venetoclax as a single-agent and in combination with azacitidine. | Measured from Cycle 1 Day 1 as long as the subject 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. |
| Complete Remission (CR) Rate | Proportion of subjects who achieved a complete remission. | Measured from Cycle 1 Day 1 as long as the subject 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 red blood cell (RBC) transfusion independence | Proportion of red blood cell (RBC) transfusion independence. | Measured from Cycle 1 Day 1 as long as the subject 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 Complete Response (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 date of first response (CR) to the to the earliest documentation of progressive disease or death of any cause, and for an anticipated maximum duration of 24 months. |
| Rate of Hematologic Improvement (HI) | Proportion of participants with HI (erythroid/platelet/neutrophil responses) | Measured from Cycle 1 Day 1 as long as the subject 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 marrow complete remission (mCR) | Proportion of participants with marrow complete remission with or without hematological improvement. | Measured from Cycle 1 Day 1 (C1D1) as long as the subject 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 ORR | Duration of response (ORR) 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 the date of first response (CR or PR) to the earliest documentation of progressive disease or death of any cause, and for an anticipated maximum duration of 24 months. |
| University of Colorado Hospital /ID# 155365 |
| Aurora |
| Colorado |
| 80045 |
| United States |
| Yale University /ID# 162544 | New Haven | Connecticut | 06510 | United States |
| Duplicate_University of Chicago /ID# 155364 | Chicago | Illinois | 60637 | United States |
| Pediatric Endocrine Associates /ID# 171227 | Boston | Massachusetts | 02114 | United States |
| Dana-Farber Cancer Institute /ID# 155361 | Boston | Massachusetts | 02215 | United States |
| University of Massachusetts - Worcester /ID# 155366 | Worcester | Massachusetts | 01655 | United States |
| Columbia Univ Medical Center /ID# 156388 | New York | New York | 10032-3725 | United States |
| Oregon Health and Science University /ID# 155360 | Portland | Oregon | 97239 | United States |
| University of Texas MD Anderson Cancer Center /ID# 155362 | Houston | Texas | 77030 | United States |
| St George Hospital /ID# 156037 | Kogarah | New South Wales | 2217 | Australia |
| Liverpool Hospital /ID# 155952 | Liverpool | New South Wales | 2170 | Australia |
| St Vincent's Hospital Melbourne /ID# 155950 | Fitzroy Melbourne | Victoria | 3065 | Australia |
| The Royal Melbourne Hospital /ID# 155949 | Parkville | Victoria | 3050 | Australia |
| Royal Perth Hospital /ID# 155951 | Perth | Western Australia | 6000 | Australia |
| Universitatsklinikum Mannheim /ID# 156038 | Mannheim | Baden-Wurttemberg | 68167 | Germany |
| Universitaetsklinikum Koeln /ID# 155519 | Cologne | North Rhine-Westphalia | 50937 | Germany |
| Universitaetsklinikum Duesseldorf /ID# 154899 | Düsseldorf | North Rhine-Westphalia | 40225 | Germany |
| Marien Hospital Duesseldorf /ID# 155518 | Düsseldorf | North Rhine-Westphalia | 40479 | Germany |
| Universitaetsklinikum Leipzig /ID# 154897 | Leipzig | Saxony | 04103 | Germany |
| Universitaetsklinikum Carl Gustav Carus an der TU Dresden /ID# 154898 | Dresden | 01307 | Germany |
| Universitaetsklinikum Halle (Saale) /ID# 158643 | Halle | 06120 | Germany |
| Klinikum rechts der Isar - Technische Universitaet Muenchen /ID# 154896 | Munich | 81675 | Germany |
| Derived |
| Franke GN, Luckemeier P, Platzbecker U. Allogeneic Stem-Cell Transplantation in Patients With Myelodysplastic Syndromes and Prevention of Relapse. Clin Lymphoma Myeloma Leuk. 2021 Jan;21(1):1-7. doi: 10.1016/j.clml.2020.10.008. Epub 2020 Oct 16. |
| ID | Term |
|---|---|
| D009190 | Myelodysplastic Syndromes |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D001855 | Bone Marrow Diseases |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C579720 | venetoclax |
| D001374 | Azacitidine |
| 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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