Venetoclax + Azacitidine vs. Induction Chemotherapy in AML
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04801797|
Recruitment Status : Recruiting
First Posted : March 17, 2021
Last Update Posted : November 17, 2022
This research is being done to assess the therapeutic activity of a promising combination (azacitidine and venetoclax) versus conventional cytotoxic chemotherapy in induction-eligible patients with acute myeloid leukemia.
This study involves the following:
- Venetoclax and azacitidine (investigational combination)
- Cytarabine and idarubicin or daunorubicin (per standard of care) or Liposomal daunorubicin and cytarabine (per standard of care)
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia||Drug: Cytarabine Drug: Idarubicin Drug: Daunorubicin Drug: Liposomal daunorubicin and cytarabine Drug: Venetoclax Drug: Azacitidine||Phase 2|
This is an open-label, multicenter, phase II randomized clinical trial to compare the therapeutic activity of conventional induction chemotherapy (7+3 regimen or liposomal daunorubicin and cytarabine) to the combination of venetoclax and azacitidine among fit, traditionally induction-eligible adults with newly diagnosed acute myeloid leukemia (AML).
The U.S. Food and Drug Administration (FDA) has approved the combinations of liposomal daunorubicin and cytarabine as well as cytarabine and idarubicin or daunorubicin as treatment options for acute myeloid leukemia (AML)
The FDA has approved the combination of venetoclax and azacitidine for people with acute myeloid leukemia (AML) that are over the age of 75 or who have comorbidities that preclude intensive induction chemotherapy.
Venetoclax may interact with BCL-2 (a protein that initiates tumor growth, disease progression, and drug resistance) and inhibit BLC-2 which can lead to cancer cell death. Azacitidine may cause cell death in rapidly dividing cells, which may lead to cancer cell death since cancer cells do not grow at a normal rate. Induction Chemotherapy which includes the drugs idarubicin or daunorubicin, cytarabine, and liposomal daunorubicin and cytarabine is the standard of care chemotherapy treatment for someone with acute myeloid leukemia (AML).
The research study procedures include screening for eligibility and study treatment, including evaluations and follow up visits.
Participants will receive study treatment for as long as they and their doctor believe they are benefitting from the study drugs. Participants will then be followed for 3 years or until they withdraw their consent to be contacted.
It is expected that about 172 people will take part in this research study.
AbbVie, a biopharmaceutical company, is supporting this research study by providing funding for the study, including one of the study drugs.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||172 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||This is an open-label, multicenter, phase II randomized clinical trial to compare the therapeutic activity of conventional induction chemotherapy (7+3 regimen or liposomal daunorubicin and cytarabine) (Standard arm) to the combination of venetoclax and azacitidine among fit, traditionally induction-eligible adults with newly diagnosed acute myeloid leukemia (AML).|
|Masking:||None (Open Label)|
|Official Title:||A Phase 2 Randomized Study Comparing Venetoclax and Azacitidine to Induction Chemotherapy for Newly Diagnosed Fit Adults With Acute Myeloid Leukemia|
|Actual Study Start Date :||May 20, 2021|
|Estimated Primary Completion Date :||January 1, 2025|
|Estimated Study Completion Date :||January 1, 2026|
Experimental: Standard of Care (Conventional Induction)
Randomized participants will receive cytarabine and idarubicin [or daunorubicin) per standard of care as follows:
Induction: cytarabine on days 1-7 and idarubicin (or daunorubicin) on days 1-3 of induction.
Second Induction (if needed): Cytarabine on days 1-5 and idarubicin (or daunorubicin) on days 1-2 of re-induction.
Consolidation (if needed): If < 60 years, cytarabine days 1,3,5 of consolidation cycles, and if ≥60 years, cytarabine days 1-5 of consolidation cycles
Those with secondary or therapy-related AML can receive liposomal daunorubicin and cytarabine (Vyxeos) per standard of care as follows:
Induction: Liposomal daunorubicin and cytarabine (Vyxeos) on Days 1,3, 5 of induction.
Second Induction (if needed): Liposomal daunorubicin and cytarabine (Vyxeos) on days 1,3 of re-induction Consolidation (if needed): liposomal daunorubicin and cytarabine (Vyxeos) on days 1,3 of consolidation cycles
Drug: Liposomal daunorubicin and cytarabine
Other Name: Vyxeos
Experimental: Investigational (Venetoclax and Azacitidine)
Participants will receive azacitidine on days 1-7 and venetoclax daily for up to (3) three 28-day study cycles and evaluated for response or benefit. If benefit/response is achieved, azacitidine on days 1-7 and venetoclax on days 1-28 (or less if deemed necessary per protocol) will be given in repeating 28-day cycles until benefit/response is no longer achieved or until patient proceeds to transplantation.
Orally by mouth
Other Name: Venclexta
Other Name: Vidaza
- Event free survival [ Time Frame: From the time from randomization to time for up to 3 years, per protocol. ]
Primary endpoint is event-free-survival of patients treated with venetoclax and azacitidine compared to patients treated with standard induction with either 7+3 regimen or liposomal daunorubicin and cytarabine
Events are described in the protocol and will include
- Progressive Disease as defined above
- Any change in therapy due to leukemic persistence.
- Transition to hospice
- Relapse following CR, CRi, or CRh
- Any death
Assessments of differences in EFS between the randomized arms will be made with the log-rank test; modeling will employ the Cox proportional hazards model. We also plan to assess the difference in estimated EFS at one year, using Kaplan-Meier estimates with standard deviation calculated by Greenwood's formula.
EFS will be assessed using the Kaplan-Meier method. EFS will be assessed with the log-rank test, and cox proportional hazards model when appropriate.
- Rate of response [ Time Frame: From the time from randomization to time for up to 6 months. ]
Evaluated overall and separately for patients with primary and secondary AML, comparisons will be based on the Fisher exact test.
CR and CRi will be assessed. Study also includes CRh as a possible response, CRh aims to describe marrow blast clearance and evidence of partial hematologic recovery not captured by current CR or CRi, criteria.
- Treatment-related toxicity [ Time Frame: Enrollment to end of treatment duration for up to 12 months. ]Assessed using CTCAE 5
- Rate of Minimal Residual Disease (MRD) negativity [ Time Frame: From time of enrollment until up to the first 6 months. ]Assessed by flow cytometry and next-generation sequencing
- 30-day mortality [ Time Frame: From the time of start of therapy until through the first 30 days. ]Analyzed using the Kaplan Meier method.
- 60-day mortality [ Time Frame: From the time of start of therapy until through the first 60 days. ]Analyzed using the Kaplan Meier method.
- Overall survival (OS) [ Time Frame: Overall Survival (OS) is defined as the time from randomization (or registration) to death due to any cause, or censored at date last known alive, or for up to 3 years. ]Survival will be summarized using the method of Kaplan Meier, and assessed using the log rank test and Cox proportional hazards when appropriate.
- Rate of stem cell transplantation (SCT) following induction [ Time Frame: From time of enrollment until up to 3 years following start of treatment. ]The proportion of patients that receive a hematopoietic stem cell transplant following induction therapy or consolidation/continuation therapy.
- Patient reported quality of life (QOL) [ Time Frame: up to one year ]To compare quality of life between the two groups using the Functional Assessment of Cancer Therapy-Leukemia (FACT-Leuk). the FACT-Leukemia ranges from 0-176 with higher scores indicating better quality of life
- Patient-reported depression symptoms [ Time Frame: up to one year ]To compare depression symptoms between the two groups using the Hospital Anxiety and Depression Scale (HADS-Depression). the HADS-depression ranges from 0 (no distress) to 21 (maximum distress) with higher scores indicating worse depression symptoms
- Patient-reported anxiety symptoms [ Time Frame: up to one year ]To compare anxiety symptoms between the two groups using the Hospital Anxieyt and Depression Scale (HADS-Anxiety). the HADS-Anxiety ranges from 0 (no distress) to 21 (maximum distress) with higher scores indicating worse anxiety symptoms
- Patient-reported symptom burden [ Time Frame: up to one year ]To compare symptom burden between the two groups using the Edmonton Symptom Assessment Scale (ESAS-revised). ESAS ranges from 0-100 with higher scores indicating worse symptom burden
- Patient-reported post-traumatic stress symptoms [ Time Frame: up to one year ]To compare post-traumatic stress (PTSD) symptoms between the two groups using the PTSD-Checklist-Civilian Version. The PTSD-Checklist ranges from 17-85 with higher scores indicating worse PTSD symptoms
- Health care utilization - hospitalizations [ Time Frame: up to 1 year ]To compare number of hospitalizations between the two groups using linear regression (and adjusting for any potential imbalances between the groups
- Health care utilization - days alive and out of the hospital [ Time Frame: up to 1 year ]To compare days alive and out of the hospital between the two groups using linear regression (and adjusting for any potential imbalances between the groups)
- Health care utilization - Intensive care unit admissions [ Time Frame: up to 1 year ]To compare intensive care unit admissions (yes vs. no) between the two groups using logistic regression (and adjusting for any potential imbalances between the groups)
- Cost of care [ Time Frame: up to 1 year ]To compare cost of care between the two groups using parametric and non-parametric tests based on distribution of the data
- Incidence of neutropenic infections [ Time Frame: Up to 8 weeks ]Number of patients that experience neutropenic fever during induction cycles (up to 2 cycles).
- 100-Day post-transplant mortality [ Time Frame: From date of transplantation through 100 days following transplantation. ]Assessed using the Kaplan Meier method
- Incidence of grade 3 or greater acute graft versus host disease (GVHD) [ Time Frame: Patients that receive a SCT will be followed post-SCT through up to 100 days. ]Assessed among patients that receive HSCT following induction.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04801797
|Contact: Amir T Fathi, MD||(617) firstname.lastname@example.org|
|United States, California|
|City of Hope||Recruiting|
|Duarte, California, United States, 91010|
|Contact: Ibrahim T Aldoss, MD 626-256-4673|
|Principal Investigator: Ibrahim T Aldoss, MD|
|University of California - Davis||Recruiting|
|Sacramento, California, United States, 95817|
|Contact: Brian Jonas, MD, PhD email@example.com|
|Principal Investigator: Brian Jonas, MD, PhD|
|United States, Massachusetts|
|Massachusetts General Hospital Cancer Center||Recruiting|
|Boston, Massachusetts, United States, 02114|
|Contact: Amir T Fathi, MD 617-724-1124 firstname.lastname@example.org|
|Principal Investigator: Amir T Fathi, MD|
|Beth Israel Deaconess Medical Center||Recruiting|
|Boston, Massachusetts, United States, 02215|
|Contact: Ajoy Dias, MD 617-667-9920 email@example.com|
|Principal Investigator: Ajoy Dias, MD|
|United States, North Carolina|
|Atrium Health Levine Cancer Institute||Recruiting|
|Charlotte, North Carolina, United States, 28204|
|Contact: Brittany K. Ragon, MD 980-442-4363|
|Principal Investigator: Brittany K. Ragon, MD|
|United States, Ohio|
|Ohio State University Medical Center||Recruiting|
|Columbus, Ohio, United States, 43210|
|Contact: Alice Mims, MD 614-293-3196|
|Principal Investigator: Alice Mims, MD|
|United States, Pennsylvania|
|University of Pennsylvania||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Alexander Perl, MD firstname.lastname@example.org|
|Principal Investigator: Alexander Perl, MD|
|Principal Investigator:||Amir T Fathi, MD||Massachusetts General Hospital|