- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03629171
Liposome-encapsulated Daunorubicin-Cytarabine and Venetoclax in Treating Participants With Relapsed, Refractory or Untreated Acute Myeloid Leukemia
Phase II Study of CPX-351 in Combination With Venetoclax in Patients With Acute Myeloid Leukemia (AML)
Study Overview
Status
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVE:
I. To assess the efficacy (complete remission [CR], complete remission without blood count recovery [CRi], complete remission without platelet recovery [CRp]) of liposome-encapsulated daunorubicin-cytarabine (CPX-351) in combination with venetoclax in patients with acute myeloid leukemia (AML).
SECONDARY OBJECTIVES:
I. To assess safety of CPX-351 in combination with venetoclax in patients with AML.
II. To assess the event free survival (EFS) and overall survival (OS) in patients with AML.
EXPLORATORY OBJECTIVE:
I. To explore biomarkers of response and resistance in AML treated with CPX-351 and venetoclax.
OUTLINE: This is a dose-escalation study of venetoclax.
INDUCTION: Participants receive liposome-encapsulated daunorubicin-cytarabine intravenously (IV) over 90 minutes on days 1, 3, and 5 of cycle 1 and on days 1 and 3 of cycle 2. Participants also receive venetoclax orally (PO) once daily (QD) on days 2-21. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Participants receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 and venetoclax PO QD on days 2-21. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, participants are followed up at 30 days and then every 3 months for 3 years.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
Contacts and Locations
Study Contact
- Name: Tapan Kadia
- Phone Number: 713-563-3534
- Email: tkadia@mdanderson.org
Study Locations
-
-
Texas
-
Houston, Texas, United States, 77030
- Recruiting
- M D Anderson Cancer Center
-
Contact:
- Tapan M. Kadia
- Phone Number: 713-792-7305
- Email: tkadia@mdanderson.org
-
Principal Investigator:
- Tapan M. Kadia
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- For the lead in phase: Patients >= 18 years of age with a diagnosis of relapsed and/or refractory AML will be eligible. Patients who have had prior treatment with venetoclax will be allowed to participate in the lead in phase and cohort A
- For the dose expansion cohort A (relapsed/refractory [R/R] AML): Patients >= 18 years of age with a diagnosis of relapsed and/or refractory AML will be eligible
- For the dose expansion cohort B (de novo AML): Patients >= 18 years to 69 years of age; patients in this cohort must have received no prior therapy for AML
- Prior therapy with hydroxyurea, hematopoietic growth factors, or tretinoin (ATRA) (for emergency use for stabilization) is allowed with no washout. A cumulative dose of ara-C of up to 3 g for emergency stabilization in patients with rapidly proliferating disease is also allowed provided it was administered > 48 hrs prior to enrollment
- Bilirubin =< 2 mg/dL
- Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =< 3 x upper limit of normal (ULN) or < 5 x ULN if related to leukemic involvement
- Creatinine =< 1.5 x ULN
- Known cardiac ejection fraction of > or = 45% within the past 3 months
- Eastern Cooperative Oncology Group (ECOG) performance status of =< 2
- A negative urine or serum pregnancy test is required within 1 week for all women of childbearing potential prior to enrolling on this trial. A woman of childbearing potential is defined as a woman who has not been naturally postmenopausal for at least 12 consecutive months, or who had no previous surgical sterilization
- Patient must have the ability to understand the requirements of the study and signed informed consent. A signed informed consent by the patient or his legally authorized representative is required prior to their enrollment on the protocol
Exclusion Criteria:
- Pregnant women are excluded from this study because the agents used in this study have the potential for teratogenic or abortifacient effects. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with the chemotherapy agents, breastfeeding should also be avoided
- Uncontrolled intercurrent illness including, but not limited to active uncontrolled infection, symptomatic congestive heart failure (New York Heart Association [NYHA] class III or IV), unstable angina pectoris, clinically significant cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Patient with documented hypersensitivity to any of the components of the chemotherapy program
- Patients with acute promyelocytic leukemia (M3) or core-binding factor AML
- Patients with active central nervous system (CNS) leukemia are excluded since the antileukemia activity of the treatment components against CNS leukemia are not known
- Men and women of childbearing potential who do not practice contraception. Women of childbearing potential and men must agree to use contraception prior to study entry and for the duration of study participation
- Prior treatment with CPX-351 or venetoclax. Patients with prior treatment with venetoclax will be allowed in patients with relapsed/refractory (R/R) disease including those in the lead-in phase as well as those in cohort A
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (CPX-351, venetoclax)
INDUCTION: Participants receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5 of cycle 1 and on days 1 and 3 of cycle 2. Participants also receive venetoclax PO QD on days 2-21. Treatment repeats every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Participants receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 and venetoclax PO QD on days 2-21. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. |
Given PO
Other Names:
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Achievement of composite complete remission
Time Frame: Up to 3 cycles (84 days)
|
Defined as complete remission/complete remission without blood count recovery/complete remission without platelet recovery.
Will be monitored simultaneously using the Bayesian approach of Thall, Simon, Estey.
Will be estimated along with the 95% credible interval.
|
Up to 3 cycles (84 days)
|
Incidence of adverse events
Time Frame: Up to 28 days
|
Will be monitored simultaneously using the Bayesian approach of Thall, Simon, Estey.
Will be summarized using descriptive statistics such as mean, standard deviation, median and range.
Safety data will be summarized by category, severity and frequency.
|
Up to 28 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Event-free survival
Time Frame: Number of days from the date of treatment initiation up to 1 year
|
Will be estimated using the method of Kaplan and Meier.
Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.
|
Number of days from the date of treatment initiation up to 1 year
|
Overall survival
Time Frame: Time from treatment start till death or last follow-up, assessed up to 1 year
|
Will be estimated using the method of Kaplan and Meier.
Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests.
|
Time from treatment start till death or last follow-up, assessed up to 1 year
|
Biomarker changes
Time Frame: Baseline up to 1 year
|
The comparison regarding biomarkers between response and non-response will be conducted by two-sample t-test if the data is normally distributed, otherwise Wilcoxon rank sum test will be used.
|
Baseline up to 1 year
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Tapan M Kadia, M.D. Anderson Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Hematologic Diseases
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Enzyme Inhibitors
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antibiotics, Antineoplastic
- Venetoclax
- Cytarabine
- Daunorubicin
Other Study ID Numbers
- 2017-1055 (Other Identifier: M D Anderson Cancer Center)
- NCI-2018-01589 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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