Recurrent Acute Myeloid LeukemiaPhase 2NCT03629171
Liposome-encapsulated Daunorubicin-Cytarabine and Venetoclax in Treating Participants With Relapsed, Refractory or Untreated Acute Myeloid Leukemia
A Phase 2 study testing Liposome-encapsulated Daunorubicin-Cytarabine and Venetoclax in people with Recurrent Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase II trial studies how well liposome-encapsulated daunorubicin-cytarabine and venetoclax work in treating participants with acute myeloid leukemia that has come back (relapsed), does not respond to treatment (refractory), or has not been treated (untreated). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
- What is being tested?
- Liposome-encapsulated Daunorubicin-Cytarabine and Venetoclax
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Oct 2018to 31 Dec 2026
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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 newly diagnosed 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
M D Anderson Cancer Center
Houston, Texas, 77030
Tapan M. Kadia, 713-792-7305, tkadia@mdanderson.org
Tapan M. Kadia
About this study
Official title: Phase II Study of CPX-351 in Combination With Venetoclax in Patients With Acute Myeloid Leukemia (AML)
This phase II trial studies how well liposome-encapsulated daunorubicin-cytarabine and venetoclax work in treating participants with acute myeloid leukemia that has come back (relapsed), does not respond to treatment (refractory), or has not been treated (untreated). Drugs used in chemotherapy, such as liposome-encapsulated daunorubicin-cytarabine and venetoclax, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.
Read the detailed description
PRIMARY OBJECTIVE:
- 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:
- 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:
- 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.
- Being tested
- Liposome-encapsulated Daunorubicin-Cytarabine, Venetoclax
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liposome-encapsulated Daunorubicin-CytarabineDrug
Also called CPX-351, Cytarabine-Daunorubicin Liposome for Injection, Daunorubicin and Cytarabine (Liposomal), Liposomal AraC-Daunorubicin CPX-351
Given IV
VenetoclaxDrug
Also called ABT-0199, ABT-199, ABT199, GDC-0199
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (CPX-351, venetoclax) | Experimental | 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. Receives: Drug: Liposome-encapsulated Daunorubicin-Cytarabine; Drug: Venetoclax |
What is being measured
The primary outcome is the main question the study is designed to answer.
Achievement of composite complete remission
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.
Measured: Up to 3 cycles (84 days)
Incidence of adverse events
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.
Measured: Up to 28 days
Secondary outcomes (3)
Event-free survival
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.
Measured: Number of days from the date of treatment initiation up to 1 year
Overall survival
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.
Measured: Time from treatment start till death or last follow-up, assessed up to 1 year
Biomarker changes
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.
Measured: Baseline up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2018
- Study start29 Oct 2018
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Recurrent Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tapan M Kadia, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03629171
- Sponsor's protocol ID
- 2017-1055
- Other IDs
- NCI-2018-01589, 2017-1055
- Status last verified
- Sep 2026
- First submitted
- 9 Aug 2018
- Last updated
- 25 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Kadia TM, Jen WY, Bataller A, Bazinet A, Borthakur G, Jabbour E, Qiao W, Short NJ, Takahashi K, Issa GC, DiNardo CD, Montalban-Bravo G, Pemmaraju N, Tran A, Bharathi V, Loghavi S, Alousi AM, Popat U, Daver NG, Ravandi F, Kantarjian HM. A Phase 2 Trial of CPX-351 Combined With Venetoclax in Relapsed or Refractory Acute Myeloid Leukemia. Am J Hematol. 2025 Aug;100(8):1365-1373. doi: 10.1002/ajh.27723. Epub 2025 May 22.
PubMed 40401707