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Liposome-encapsulated Daunorubicin-Cytarabine and Venetoclax in Treating Participants With Relapsed, Refractory or Untreated Acute Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT03629171
Recruitment Status : Recruiting
First Posted : August 14, 2018
Last Update Posted : September 6, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief 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, does not respond to treatment, or has not been treated. 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.

Condition or disease Intervention/treatment Phase
Recurrent Acute Myeloid Leukemia Refractory Acute Myeloid Leukemia Untreated Adult Acute Myeloid Leukemia Drug: Liposome-encapsulated Daunorubicin-Cytarabine Drug: Venetoclax Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

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 OBJECTIVES:

I. To explore biomarkers of response and resistance in AML treated with CPX-351 and venetoclax.

OUTLINE:

INDUCTION: Participants receive liposome-encapsulated daunorubicin-cytarabine intravenously (IV) over 90 minutes on days 1, 3, and 5 of course 1 and on days 1 and 3 of course 2. Participants also receive venetoclax orally (PO) once daily (QD) on days 2-21. Treatment repeats every 28 days for up to 2 courses 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 courses 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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 52 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of CPX-351 in Combination With Venetoclax in Patients With Acute Myeloid Leukemia (AML)
Actual Study Start Date : October 29, 2018
Estimated Primary Completion Date : June 30, 2020
Estimated Study Completion Date : June 30, 2020


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 course 1 and on days 1 and 3 of course 2. Participants also receive venetoclax PO QD on days 2-21. Treatment repeats every 28 days for up to 2 courses 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 courses in the absence of disease progression or unacceptable toxicity.

Drug: Liposome-encapsulated Daunorubicin-Cytarabine
Given IV
Other Names:
  • CPX-351
  • Cytarabine-Daunorubicin Liposome for Injection
  • Liposomal AraC-Daunorubicin CPX-351
  • Liposomal Cytarabine-Daunorubicin
  • Liposome-encapsulated Combination of Daunorubicin and Cytarabine
  • Vyxeos

Drug: Venetoclax
Given PO
Other Names:
  • ABT-0199
  • ABT-199
  • ABT199
  • GDC-0199
  • RG7601
  • Venclexta




Primary Outcome Measures :
  1. Achievement of composite complete remission [ Time Frame: Up to 3 courses (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.

  2. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  • 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 65 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 the lead-in phase

Information from the National Library of Medicine

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): NCT03629171


Contacts
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Contact: Tapan Kadia 713-563-3534 tkadia@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Tapan M. Kadia    713-563-3534      
Principal Investigator: Tapan M. Kadia         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Tapan M Kadia M.D. Anderson Cancer Center

Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT03629171     History of Changes
Other Study ID Numbers: 2017-1055
NCI-2018-01589 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2017-1055 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
First Posted: August 14, 2018    Key Record Dates
Last Update Posted: September 6, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Venetoclax
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Daunorubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors