Description:
Myelodysplastic Syndrome (MDS) is a group of disorders that gradually affect the ability of a
person's bone marrow (semi-liquid tissue present in many bones like backbones) to produce
normal blood cells. Some people with MDS have a risk of the disease progressing to acute
myeloid leukemia (AML), and a risk of death from the disease itself. Symptoms of MDS include
fatigue, shortness of breath, unusual paleness due to anemia (low red blood cell count), easy
or unusual bruising, and red spots just beneath the skin caused by bleeding. The purpose of
this study is to see how safe and effective venetoclax and azacitidine (AZA) combination are
when compared to AZA and a placebo (contains no medicine), in participants with newly
diagnosed higher-risk MDS.
Venetoclax is an investigational drug being developed for the treatment of MDS. The study
consists of two treatment arms - In one arm, participants will receive venetoclax and AZA. In
another arm, participants will receive AZA and placebo. Adult participants with newly
diagnosed higher-risk MDS will be enrolled. Around 500 participants will be enrolled in
approximately 220 sites worldwide.
Participants in one arm will receive oral doses of venetoclax tablet and intravenous
(infusion in the vein) or subcutaneous (given under the skin) AZA solution. Participants in
another arm will receive oral doses of placebo tablet and intravenous or subcutaneous AZA
solution.
There may be higher treatment burden for participants in this trial compared to their
standard of care. Participants will attend regular visits during the course of the study at a
hospital or clinic. The effect of the treatment will be checked by medical assessments, blood
and bone marrow tests, checking for side effects, and completing questionnaires.
Title
- Brief Title: Study Of Venetoclax Tablet With Intravenous or Subcutaneous Azacitidine to Assess Change in Disease Activity In Adult Participants With Newly Diagnosed Higher-Risk Myelodysplastic Syndrome
- Official Title: A Randomized, Double-Blind, Phase 3 Study Evaluating the Safety and Efficacy of Venetoclax in Combination With Azacitidine in Patients Newly Diagnosed With Higher-Risk Myelodysplastic Syndrome (Higher-Risk MDS)
Clinical Trial IDs
- ORG STUDY ID:
M15-954
- SECONDARY ID:
2020-000744-55
- NCT ID:
NCT04401748
Conditions
- Myelodysplastic Syndrome (MDS)
Interventions
| Drug | Synonyms | Arms |
|---|
| Venetoclax | ABT-199, GDC-0199, Venclexta | Arm 1: Venetoclax + Azacitidine (AZA) |
| Azacitidine | AZA | Arm 1: Venetoclax + Azacitidine (AZA) |
| Placebo | | Arm 2: Placebo + Azacitidine |
Purpose
Myelodysplastic Syndrome (MDS) is a group of disorders that gradually affect the ability of a
person's bone marrow (semi-liquid tissue present in many bones like backbones) to produce
normal blood cells. Some people with MDS have a risk of the disease progressing to acute
myeloid leukemia (AML), and a risk of death from the disease itself. Symptoms of MDS include
fatigue, shortness of breath, unusual paleness due to anemia (low red blood cell count), easy
or unusual bruising, and red spots just beneath the skin caused by bleeding. The purpose of
this study is to see how safe and effective venetoclax and azacitidine (AZA) combination are
when compared to AZA and a placebo (contains no medicine), in participants with newly
diagnosed higher-risk MDS.
Venetoclax is an investigational drug being developed for the treatment of MDS. The study
consists of two treatment arms - In one arm, participants will receive venetoclax and AZA. In
another arm, participants will receive AZA and placebo. Adult participants with newly
diagnosed higher-risk MDS will be enrolled. Around 500 participants will be enrolled in
approximately 220 sites worldwide.
Participants in one arm will receive oral doses of venetoclax tablet and intravenous
(infusion in the vein) or subcutaneous (given under the skin) AZA solution. Participants in
another arm will receive oral doses of placebo tablet and intravenous or subcutaneous AZA
solution.
There may be higher treatment burden for participants in this trial compared to their
standard of care. Participants will attend regular visits during the course of the study at a
hospital or clinic. The effect of the treatment will be checked by medical assessments, blood
and bone marrow tests, checking for side effects, and completing questionnaires.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Arm 1: Venetoclax + Azacitidine (AZA) | Experimental | Participants will receive venetoclax once daily (QD) (Days 1-14) in combination with AZA QD (7 days of the first 9 days) of each 28 day cycle. | |
| Arm 2: Placebo + Azacitidine | Active Comparator | Participants will receive placebo once daily (QD) (Days 1-14) in combination with AZA QD (7 days of the first 9 days) of each 28 day cycle. | |
Eligibility Criteria
Inclusion Criteria:
- Participants with a diagnosis of Myelodysplastic Syndrome (MDS) according to the 2016
World Health Organization (WHO) classification wtih presence of < 20% bone marrow
blasts per marrow biopsy/aspirate at screening.
- Participants must meet the following disease activity criteria:
- Overall Revised International Prognostic Scoring System (IPSS-R) score > 3
(intermediate, high or very high).
- Eastern Cooperative Oncology Group (ECOG) performance status of <= 2.
- Hematopoietic stem cell transplant (HSCT) eligible with no pre-arranged HSCT at
the time of Study Day 1, or HSCT ineligible without plan for HSCT at the time of
Study Day 1.
Exclusion Criteria:
- Prior therapy for MDS with any hypomethylating agent, chemotherapy, or allogenic stem
cell transplantation.
- Prior diagnosis of therapy-related MDS (t-MDS), MDS evolving from a pre-existing
myeloproliferative neoplasm (MPN), MDS/MPN including chronic myelomonocytic leukemia
(CMML), atypical chronic myeloid leukemia (aCML), juvenile myelomonocytic leukemia
(JMML) and unclassifiable MDS/MPN.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | Complete Remission (CR) |
| Time Frame: | Up To 36 Months |
| Safety Issue: | |
| Description: | CR is defined as achieving a complete remission at any time point during the study per the modified International Working Group (IWG) 2006 criteria for myelodysplastic syndrome (MDS). |
Secondary Outcome Measures
| Measure: | Percentage of Participants Achieving Transfusion Independence (TI) Who are Transfusion Dependent at Baseline |
| Time Frame: | Up To 5 Years |
| Safety Issue: | |
| Description: | TI is when the participants who were transfusion dependent on RBC and/or Platelet at baseline achieve transfusion independence post baseline. TI is a period of at least 56 days with no transfusion after the date of the first dose of study drug to the last dose of study drug + 30 days, the initiation of post-treatment therapy, or death, whichever is earliest. |
| Measure: | Change in Patient-Reported Outcomes Measurement Information System (PROMIS)-Fatigue Short Form (SF) 7a Scale Score |
| Time Frame: | Up To 5 Years |
| Safety Issue: | |
| Description: | Fatigue will be assessed using the PROMIS Fatigue SF 7a Global Fatigue Score. PROMIS Fatigue SF 7a is a 7-item questionnaire that assesses the impact and experience of fatigue over the past 7 days. Participants rate items on a 5-point scale, with 1 as "never" an 5 as "always". |
| Measure: | Time to Deterioration in Physical Functioning as Measured by Physical Functioning Domain of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) Scale |
| Time Frame: | Up To 5 Years |
| Safety Issue: | |
| Description: | Time to deterioration in physical functioning, as measured by the EORTC QLQ-C30 physical functioning score is defined as the time from the date of randomization to the date of death of any cause, or the first time worsening of score from baseline >= a pre-specified threshold. Participants rate items on a 4-point scale, with 1 as "not at all" and 4 as "very much." |
| Measure: | Overall Response (OR) |
| Time Frame: | Up To 5 Years |
| Safety Issue: | |
| Description: | OR [complete remission (CR) + partial response (PR)] is defined as achieving a CR or PR at any time point during the study per the modified IWG 2006 criteria for MDS. |
| Measure: | Modified Overall Response (mOR) |
| Time Frame: | Up To 5 Years |
| Safety Issue: | |
| Description: | mOR [complete remission (CR) + marrow complete remission (mCR) + partial response (PR)] is defined as achieving a CR, mCR, or PR at any time point during the study per the modified IWG 2006 criteria for MDS. |
Details
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | AbbVie |
Trial Keywords
- MDS
- Myelodysplastic Syndrome
- Venetoclax
- Azacitidine
- AZA
- Venclexta
Last Updated
August 26, 2021
