Recurrent Acute Myeloid LeukemiaPhase 2NCT03825796
CPX-351 Plus Enasidenib for Relapsed AML
A Phase 2 study testing Enasidenib Mesylate and Liposome-encapsulated Daunorubicin-Cytarabine in people with Recurrent Acute Myeloid Leukemia, run by Jonsson Comprehensive Cancer Center at 3 sites in United States.
Trial summary
This trial evaluates how well CPX-351 and enasidenib work in treating patients with acute myeloid leukemia characterized by IHD2 mutation. Drugs used in chemotherapy, such as CPX-351, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Recurrent Acute Myeloid Leukemia
- What is being tested?
- Enasidenib Mesylate and Liposome-encapsulated Daunorubicin-Cytarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 3 sitesUnited States
- Study dates
- 12 Apr 2019to 1 Sep 2024
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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
- Bone marrow blasts >= 5% that develops after CR/CRi in patient with prior history of AML, no restriction on prior number of relapses or regimens
- AML characterized by the IDH2 gene mutation, without requirement for a particular allelic frequency
- Patients previously treated with IDH2 inhibitor can be enrolled
- At least a 3-month duration of CR/CRi prior to relapse
- Relapses after allogeneic HSCT are included with a minimum of 3 from the date of allogeneic HSCT
- Up to 1 cycle of hypomethylating agent monotherapy at time of relapse is allowed, must be discontinued at least 14 days prior to start of salvage induction
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- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Serum total bilirubin < 2.0 mg/dL, unless considered due to Gilbert's disease or leukemic involvement
- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) < 3 times the upper limit of normal, unless considered due to leukemic involvement
- Alkaline phosphatase < 3 times the upper limit of normal, unless considered due to leukemic involvement
- Serum creatinine =< 2.0 mg/dL, or creatinine clearance > 40 mL/min based on Cockcroft-Gault glomerular filtration rate (GFR)
- Females of reproductive potential as well as fertile men and their partners who are female of reproductive potential must agree to abstain from sexual intercourse or to use two highly effective forms of contraception from the time of giving informed consent, during the study, and for four months (females and males) following the last dose of IDH inhibitor. A highly effective form of contraception is defined as hormonal oral contraceptives, injectables, patches, intrauterine devices, double-barrier method (eg, synthetic condoms, diaphragm or cervical cap with spermicidal foam, cream, or gel) or male partner sterilization
Who cannot join
- Concurrent FLT3 mutation that the treating physician deems necessary to treat with FLT3-targeted therapy; whereas, patients with FLT3-mutated AML not treated with FLT3-targeted therapy can be enrolled
- Acute promyelocytic leukemia
- Inability to swallow medications or history of gastrointestinal (GI) malabsorptive disease
- Active malignancy that would limit survival by less than two years
- New York Heart Association class III or VI
- Left ventricular ejection fraction < 40%
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- History of coronary stent placement that require mandatory continuation of dual-antiplatelet therapy
- Baseline QT corrected interval based on Fridericia's formula (QTcF) interval > 450 ms
- History of Wilson's disease or other copper handling disorders
- Hypersensitivity to cytarabine, daunorubicin, or liposomal products
- Active invasive fungal infection
- Active bacterial or viral infection manifesting as fevers or hemodynamic instability within the past 72 hours
- Lifetime cumulative daunorubicin-equivalent anthracycline dose > 368 mg/m^2
- Pregnant or breast feeding
Trial locations and contacts
3 sites in 1 country.
United States3 sites
UCLA / Jonsson Comprehensive Cancer Center
Los Angeles, California, 90095
University of California Davis Comprehensive Cancer Center
Sacramento, California, 95817
University of California San Diego
San Diego, California, 92103
About this study
Official title: CPX-351 Plus Enasidenib for Relapsed Acute Myelogenous Leukemia Characterized by the IDH2 Mutation
This trial evaluates how well CPX-351 and enasidenib work in treating patients with acute myeloid leukemia characterized by IHD2 mutation. Drugs used in chemotherapy, such as CPX-351, 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. Enasidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving CPX-351 and enasidenib may work better in treating patients with acute myeloid leukemia, compared to giving only one of these therapies alone.
Read the detailed description
PRIMARY OBJECTIVE:
- To estimate the remission rate (defined as complete remission [CR]/ CR with incomplete hematologic recovery [CRi]) of the combination of liposome-encapsulated daunorubicin-cytarabine (CPX-351) plus enasidenib mesylate (enasidenib) in adults with relapsed acute myeloid leukemia (AML) characterized by a 2-hydroxyglutarate (2-HG) producing IDH2 mutations that include IDH2^R172 and IDH2^R140.
SECONDARY OBJECTIVES:
- To evaluate persistent severe hematologic toxicity at induction day 60 in patients with a morphologic leukemia-free state (bone marrow blasts < 5%).
II. To evaluate delayed CR/CRi with enasidenib maintenance in participants with stable disease after induction with CPX-351.
III. To estimate the rate of CR plus complete remission with partial hematologic recovery (CRp) of the combination of CPX-351 plus enasidenib.
IV. To evaluate time to return of normal hematopoiesis after induction therapy. V. To evaluate 30- and 60-day survival. VI. To evaluate CPX-351 plus enasidenib as a bridge to allogeneic hematopoietic stem cell transplantation (HSCT).
EXPLORATORY OBJECTIVES:
- To determine the co-existing mutations that are present with the IDH2 mutation and describe those that are present in patients who achieve CR/CRi.
II. To determine the depth of molecular response to induction by minimal residual disease (MRD) using next generation sequencing.
III. To estimate the subclinical cardiotoxicity of CPX-351 as measured by troponin I, electrocardiography (ECG), and echocardiography.
OUTLINE:
INDUCTION: Patients receive liposome-encapsulated daunorubicin-cytarabine intravenously (IV) over 90 minutes on days 1, 3, and 5, and enasidenib mesylate orally (PO) on days 10-60 in the absence of disease progression or unacceptable toxicity. Patients whose bone marrow is not hypoplastic receive re-induction including liposome-encapsulated daunorubicin-cytarabine IV on days 1 and 3, and enasidenib mesylate PO on days 8-60 in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Participants who achieve CR/CRi may proceed directly to allogeneic HSCT or receive up to 4 cycles of consolidation. Patients < 60 years receive cytarabine twice daily (BID) on days 1, 3, and 5, and patients >= 60 years receive cytarabine IV once daily on days 1-5. Patients also receive enasidenib mesylate PO on days 6-55. Treatment repeats every 28-55 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who maintain CR/CRi after completion of consolidation therapy undergo allogeneic HSCT at the discretion of the treating physician.
MAINTENANCE: Participants who have stable disease (not meeting criteria for progressive disease, but also not achieving CR/CRi) at day 60 receive enasidenib mesylate PO daily in the absence of disease progression or unacceptable toxicity. Routine follow-up visits will be conducted at least once every 3 months for the duration of the trial.
- Conditions
- Recurrent Acute Myeloid Leukemia
- Being tested
- Enasidenib Mesylate, Liposome-encapsulated Daunorubicin-Cytarabine
- 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.
Enasidenib MesylateDrug
Also called 2-Methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol Methanesulfonate, 2-Propanol, 2-Methyl-1-((4-(6-(trifluoromethyl)-2-pyridinyl)-6-((2-(trifluoromethyl)-4-pyridinyl)amino)-1,3,5-triazin-2-yl)amino)-, Methanesulfonate (1:1), AG-221 Mesylate, CC-90007
Given PO
Liposome-encapsulated Daunorubicin-CytarabineDrug
Also called CPX-351, Cytarabine-Daunorubicin Liposome for Injection, Liposomal AraC-Daunorubicin CPX-351, Liposomal Cytarabine-Daunorubicin
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (CPX-351, enasidenib mesylate) | Experimental | See detailed description Receives: Drug: Enasidenib Mesylate; Drug: Liposome-encapsulated Daunorubicin-Cytarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete remission (CR)/CR with incomplete hematologic recovery (CRi) after induction therapy
Measured: Up to day 60
Secondary outcomes (6)
Proportion of patients with persistent grade 4 hematologic toxicity per Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
The proportion along with the exact 95% confidence interval will reported.
Measured: At day 60
Proportion of patients who achieve CR/CRi during maintenance therapy
This is calculated only among patients who had stable disease after induction therapy and have received maintenance enasidenib monotherapy.
Measured: Up to 2 years
Proportion of patients who achieve CR/complete remission with partial hematologic recovery (CRp) after induction therapy
Measured: Up to 2 years
Time to return of normal hematopoiesis
Defined as time from day 1 of induction to absolute neutrophil count (ANC) >= 1000/uL and platelet count >= 100,000/uL. The median time to return of normal hematopoiesis will be reported along with the corresponding range.
Measured: From day 1 of induction assessed up to 2 years
Overall survival
Will be estimated using Kaplan-Meier methods. The survival estimate at these two time points will be reported along with a 95% confidence interval.
Measured: From day 1 of induction therapy, assessed at day 30 and 60
Proportion of patients who go on to receive allogeneic hematopoietic stem cell transplantation (HSCT) after achieving CR/CRi
Will be reported along with an exact 95% confidence interval.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2019
- Study start12 Apr 2019
- Primary completion1 Sep 2024 (estimated)
- Study completion1 Sep 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- 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
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jonsson Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- Jazz Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Caspian Oliai, MD, Principal investigator, UCLA / Jonsson Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03825796
- Sponsor's protocol ID
- 18-001416
- Other IDs
- NCI-2018-02998
- Status last verified
- Sep 2023
- First submitted
- 30 Jan 2019
- Last updated
- 28 Sep 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- CPX-351 Plus Enasidenib for Relapsed Acute Myelogenous Leukemia Characterized by the IDH2 Mutation
- ClinicalTrials.gov ID
- NCT03825796
- Acronym / sponsor ID
- 18-001416
- Conditions
- Recurrent Acute Myeloid Leukemia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Jonsson Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- Jazz Pharmaceuticals
- Study start
- 12 Apr 2019 (actual)
- Primary completion
- 1 Sep 2024 (estimated)
- Study completion
- 1 Sep 2024 (estimated)
- First posted
- 31 Jan 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial evaluates how well CPX-351 and enasidenib work in treating patients with acute myeloid leukemia characterized by IHD2 mutation. Drugs used in chemotherapy, such as CPX-351, 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. Enasidenib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving CPX-351 and enasidenib may work better in treating patients with acute myeloid leukemia, compared to giving only one of these therapies alone.
Detailed description
PRIMARY OBJECTIVE:
- To estimate the remission rate (defined as complete remission [CR]/ CR with incomplete hematologic recovery [CRi]) of the combination of liposome-encapsulated daunorubicin-cytarabine (CPX-351) plus enasidenib mesylate (enasidenib) in adults with relapsed acute myeloid leukemia (AML) characterized by a 2-hydroxyglutarate (2-HG) producing IDH2 mutations that include IDH2^R172 and IDH2^R140.
SECONDARY OBJECTIVES:
- To evaluate persistent severe hematologic toxicity at induction day 60 in patients with a morphologic leukemia-free state (bone marrow blasts < 5%).
II. To evaluate delayed CR/CRi with enasidenib maintenance in participants with stable disease after induction with CPX-351.
III. To estimate the rate of CR plus complete remission with partial hematologic recovery (CRp) of the combination of CPX-351 plus enasidenib.
IV. To evaluate time to return of normal hematopoiesis after induction therapy. V. To evaluate 30- and 60-day survival. VI. To evaluate CPX-351 plus enasidenib as a bridge to allogeneic hematopoietic stem cell transplantation (HSCT).
EXPLORATORY OBJECTIVES:
- To determine the co-existing mutations that are present with the IDH2 mutation and describe those that are present in patients who achieve CR/CRi.
II. To determine the depth of molecular response to induction by minimal residual disease (MRD) using next generation sequencing.
III. To estimate the subclinical cardiotoxicity of CPX-351 as measured by troponin I, electrocardiography (ECG), and echocardiography.
OUTLINE:
INDUCTION: Patients receive liposome-encapsulated daunorubicin-cytarabine intravenously (IV) over 90 minutes on days 1, 3, and 5, and enasidenib mesylate orally (PO) on days 10-60 in the absence of disease progression or unacceptable toxicity. Patients whose bone marrow is not hypoplastic receive re-induction including liposome-encapsulated daunorubicin-cytarabine IV on days 1 and 3, and enasidenib mesylate PO on days 8-60 in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION: Participants who achieve CR/CRi may proceed directly to allogeneic HSCT or receive up to 4 cycles of consolidation. Patients < 60 years receive cytarabine twice daily (BID) on days 1, 3, and 5, and patients >= 60 years receive cytarabine IV once daily on days 1-5. Patients also receive enasidenib mesylate PO on days 6-55. Treatment repeats every 28-55 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients who maintain CR/CRi after completion of consolidation therapy undergo allogeneic HSCT at the discretion of the treating physician.
MAINTENANCE: Participants who have stable disease (not meeting criteria for progressive disease, but also not achieving CR/CRi) at day 60 receive enasidenib mesylate PO daily in the absence of disease progression or unacceptable toxicity. Routine follow-up visits will be conducted at least once every 3 months for the duration of the trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (CPX-351, enasidenib mesylate) | Experimental | Drug: Enasidenib Mesylate, Drug: Liposome-encapsulated Daunorubicin-CytarabineSee detailed description |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Bone marrow blasts >= 5% that develops after CR/CRi in patient with prior history of AML, no restriction on prior number of relapses or regimens
- AML characterized by the IDH2 gene mutation, without requirement for a particular allelic frequency
- Patients previously treated with IDH2 inhibitor can be enrolled
- At least a 3-month duration of CR/CRi prior to relapse
- Relapses after allogeneic HSCT are included with a minimum of 3 from the date of allogeneic HSCT
Key exclusion criteria (14 listed)
- Concurrent FLT3 mutation that the treating physician deems necessary to treat with FLT3-targeted therapy; whereas, patients with FLT3-mutated AML not treated with FLT3-targeted therapy can be enrolled
- Acute promyelocytic leukemia
- Inability to swallow medications or history of gastrointestinal (GI) malabsorptive disease
- Active malignancy that would limit survival by less than two years
- New York Heart Association class III or VI
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Enasidenib MesylateAlso: 2-Methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol Methanesulfonate, 2-Propanol, 2-Methyl-1-((4-(6-(trifluoromethyl)-2-pyridinyl)-6-((2-(trifluoromethyl)-4-pyridinyl)amino)-1,3,5-triazin-2-yl)amino)-, Methanesulfonate (1:1), AG-221 Mesylate, CC-90007Given PO | Drug | Treatment (CPX-351, enasidenib mesylate) |
| Liposome-encapsulated Daunorubicin-CytarabineAlso: CPX-351, Cytarabine-Daunorubicin Liposome for Injection, Liposomal AraC-Daunorubicin CPX-351, Liposomal Cytarabine-DaunorubicinGiven IV | Drug | Treatment (CPX-351, enasidenib mesylate) |
Primary outcome
Complete remission (CR)/CR with incomplete hematologic recovery (CRi) after induction therapy
Time frame: Up to day 60
6 secondary outcomes
Proportion of patients with persistent grade 4 hematologic toxicity per Common Terminology Criteria for Adverse Events (CTCAE) version 4.03
Time frame: At day 60
Proportion of patients who achieve CR/CRi during maintenance therapy
Time frame: Up to 2 years
Proportion of patients who achieve CR/complete remission with partial hematologic recovery (CRp) after induction therapy
Time frame: Up to 2 years
Time to return of normal hematopoiesis
Time frame: From day 1 of induction assessed up to 2 years
Overall survival
Time frame: From day 1 of induction therapy, assessed at day 30 and 60
Proportion of patients who go on to receive allogeneic hematopoietic stem cell transplantation (HSCT) after achieving CR/CRi
Time frame: Up to 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Caspian Oliai, MD principal investigator
UCLA / Jonsson Comprehensive Cancer Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Enasidenib Mesylate and Liposome-encapsulated Daunorubicin-Cytarabine in people with Recurrent Acute Myeloid Leukemia, run by Jonsson Comprehensive Cancer Center at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 28 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete remission (CR)/CR with incomplete hematologic recovery (CRi) after induction therapy (time frame: Up to day 60). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Sep 2023.