Acute Myeloid LeukemiaPhase 1/2NCT03844997
Phase I/II Trial of CPX-351 + Palbociclib in Patients With Acute Myeloid Leukemia
A Phase 1/2 study testing Palcociclib and CPX-351 in people with Acute Myeloid Leukemia and AML, run by Sudipto Mukherjee, MD, PhD, MPH at 1 site in United States.
Trial summary
The purpose of this study is to evaluate the safety and tolerability of Palbociclib in combination with investigational (experimental) drug, CPX-351 and evaluate the efficacy of Palbociclib in combination with chemotherapy as measured by overall response rate (ORR), i.e. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Acute Myeloid Leukemia, AML
- What is being tested?
- Palcociclib and CPX-351
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Jun 2019to 24 Jan 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Newly diagnosed acute myeloid leukemia according to 2016 WHO criteria(excluding APL [AML-M3]).
- Eastern Cooperative Oncology Group (ECOG) Performance Status <2
- Subjects must have normal organ function as defined below:
- Total bilirubin <2 times upper limit of normal ((≤ 3 x ULN if considered to be due to leukemic involvement or Gilbert's syndrome) or if higher than 2 times upper limit of normal with approval from the PI
- Serum Creatinine <2 x ULNor if higher than 2 times upper limit of normal with approval from the PI
- Left ventricular ejection fraction of ≥45%
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- Patients with secondary AML arising out of MDS (all subtypes under WHO classification), chronic myelomonocytic leukemia (CMML) and therapy-related AML are eligible.
- Women of childbearing potential should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment. All men and women of childbearing potential must use acceptable methods of birth control throughout the study
- Subjects must have the ability to understand and the willingness to sign a written informed consent document.
Who cannot join
- Prior treatment with CPX-351, Palbociclib or other cell cycle inhibitors.
- Any serious medical condition, laboratory abnormality, or psychiatric illness that, in the view of the treating physician, would place the participant at an unacceptable risk if he or she were to participate in the study or would prevent that person from giving informed consent.
- Any active malignancy (unrelated, non-hematological malignancy) diagnosed within the past 6 months of starting the study drug (other than curatively treated carcinoma-in-situ of the cervix or non-melanoma skin cancer).
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to CPX-351, Palbociclib or other cell cycle inhibitors.
- Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Known history of HIV or active hepatitis B or C.
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- No major surgery within 2 weeks prior to study enrollment.
- Pregnancy or breast feeding
- Male and female patients who are fertile who do not agree to use an effective barrier methods of birth control (i.e. abstinence) to avoid pregnancy while receiving study treatment.
- Acute promyelocytic leukemia (APL)
Trial locations and contacts
1 site in 1 country.
United States1 site
Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
Cleveland, Ohio, 44195
About this study
The purpose of this study is to evaluate the safety and tolerability of Palbociclib in combination with investigational (experimental) drug, CPX-351 and evaluate the efficacy of Palbociclib in combination with chemotherapy as measured by overall response rate (ORR), i.e. complete response (CR) and CR with incomplete blood count recovery (CRi) by 2003 IWG criteria.
Read the detailed description
The objectives of this study are to evaluate the safety and tolerability of Palbociclibin combination with CPX-351, and to evaluate the efficacy of Palbociclibin combination with chemotherapy as measured by overall response rate (ORR), i.e. complete response (CR) and CR with incomplete blood count recovery (CRi) by IWG criteria.
CPX-351 is an investigational drug that works as formulation of a fixed combination of the antineoplastic (acting to prevent, inhibit or halt the development of a neoplasm (a tumor)) drugs cytarabine and daunorubicin.
Palbociclibis an investigational drug that works to induce early G1 arrest by inhibiting CDK4/6, which are two types of CDKs that are overexpressed in AML cell cancer lines.
CPX-351 and Palbociclib is experimental because it is not approved by the Food and Drug Administration (FDA).
This is a single arm, open label study of the combination of Palbociclib with CPX-351 in adults with AML. The trial consists of two components: phase I to evaluate the safety with dose escalation of Palbociclib in combination with CPX-351 and phase II to evaluate the overall response rate of the combination in the targeted participant population.
- Conditions
- Acute Myeloid Leukemia, AML
- Being tested
- Palcociclib, CPX-351
- 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.
PalcociclibDrug
Also called IBRANCE
Palbociclib is an investigational (experimental) drug that works to induce early G1 arrest by inhibiting CDK4/6, which are two types of CDKs that are overexpressed in AML cell cancer lines. Palbociclib is experimental because it is not approved by the Food and Drug Administration (FDA).
Palbociclib will be supplied as capsules or tablets containing 125 mg equivalents of Palbociclib free base
CPX-351Drug
Also called VYXEOS
CPX-351 (daunorubicin and cytarabine) liposome for injection is a combination of daunorubicin and cytarabine in a 1:5 molar ratio encapsulated in liposomes for intravenous administration. CPX-351 is an investigational (experimental) drug that works as formulation of a fixed combination of the antineoplastic drugs cytarabine and daunorubicin. CPX-351 is experimental because it is not approved by the Food and Drug Administration (FDA).
| Study group | Role | What they receive |
|---|---|---|
| Palbociclib + CPX-351 | Experimental | Palbociclib will be administered orally on day -1 and -2 at 125 mg PO during the phase IIaportion (dose level 0).Day 0 will be rest and then CPX-351 at 100 u/m2 will be started on days 1, 3, and 5 along with Palbociclib day 2, 4, and 6 followed by rest/monitoring period (day 7-28).
If Grade 3-4 non-hematologic toxicity is observed in 1 or less of 6 patients treated, the study will move to Phase IIb. If Grade 3-4 non-hematologic toxicity is observed in 2 or more of 6 patients treated, 6 additional patients will be treated on the Phase IIa portion at a lower dose level (100 mg po) until a Phase IIb safe dose schedule is defined at which 1 or less out of 6 patients on the Phase IIa experience Grade 3-4 non-hematologic toxicity. After the Phase IIa portion ensures safety, the study will proceed with phase IIb. The phase IIb component is a Simon 2-stage design trial whose objective is to assess the clinical efficacy of the combination of Palbociclib and CPX-351. Receives: Drug: Palcociclib; Drug: CPX-351 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability of Experimental Dose of Palbociclibin Combination With CPX-351 as Measured by Number of Participants With Dose Limiting Toxicities.
If Grade 3-4 non-hematologic toxicity is observed in 1 or less of 6 patients treated, the dose of the study drug will be considered safe/tolerable. If Grade 3-4 non-hematologic toxicity is observed in 2 or more of 6 patients treated, 6 additional patients will be treated on the Phase IIa portion at a lower dose level (100 mg po).
Measured: Between days 28-35 of starting treatment
Efficacy of Palbociclibin Combination With Chemotherapy as Measured by Overall Response Rate (ORR).
Efficacy of Palbociclibin combination with chemotherapy as measured by overall response rate (ORR) which is defined as complete response (CR) and CR with incomplete blood count recovery (CRi) by IWG criteria.
Complete remission is defined as: Bone marrow blasts <5%; absence ofcirculating blasts and blasts with Auerrods; absence of extramedullarydisease; absolute neutrophil count >1.0x 109/L (1,000/μL); platelet count >100 x109/L (100,000/μL)
and
CR with incomplete blood count recovery is defined as: All CR criteria except for residualneutropenia [<1.0 x 109/L (1,000/μL)] orthrombocytopenia [<100 x 109/L(100,000/μL)].
Either of these responses will constitute ORR.
Measured: Up to 2 years from end of treatment, up to 27 months
Secondary outcomes (4)
Time to Response (TTR)
TTR is defined as the time it takes from the start date of the treatment to the date of achievement of response (as per the definition of response mentioned in the 2003 IWG criteria).
Measured: Up to 2 years from end of treatment
Duration of Response (DOR)
DOR is measured between the date of response to date of loss of response.
Measured: Up to 2 years from end of treatment
Event-free Survival (EFS)
EFS measured from the date of entry into a study to the date of primary refractory disease, or relapse from CR, or CRi, or death from any cause; patients not known to have any of these events are censored on the date they were last examined
Measured: Up to 2 years from end of treatment
Overall Survival (OS) Probability
OS probability measured from the date of entry into a clinical trial to the date of death from any cause; patients not known to have died at last follow-up are censored on the date they were last known to be alive
Measured: Up to 2 years from end of treatment, up to 27 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2019
- Study start6 Jun 2019
- Primary completion24 Jan 2024
- Study completion24 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Model description
- This is a single arm, open label study of the combination of Palbociclib with CPX-351 in adults with AML. The trial consists of two components: phase I to evaluate the safety with dose escalation of Palbociclib in combination with CPX-351 and phase II to evaluate the overall response rate of the combination in the targeted patient population. A cycle is 28 days.
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sudipto Mukherjee, MD, PhD, MPH
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Sudipto Mukherjee, MD, PhD, MPH, Case Comprehensive Cancer Center
- Investigators
- Sudipto Mukherjee, MD, PhD, Principal investigator, Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03844997
- Sponsor's protocol ID
- CASE1918
- Status last verified
- May 2025
- First submitted
- 28 Jan 2019
- Last updated
- 31 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- 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 31 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Trial of CPX-351 + Palbociclib in Patients With Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT03844997
- Acronym / sponsor ID
- CASE1918
- Conditions
- Acute Myeloid Leukemia, AML
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Sudipto Mukherjee, MD, PhD, MPHUniversity, hospital or other
- Study start
- 6 Jun 2019 (actual)
- Primary completion
- 24 Jan 2024 (actual)
- Study completion
- 24 Jan 2024 (actual)
- First posted
- 19 Feb 2019 (actual)
- Results
- Posted 31 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety and tolerability of Palbociclib in combination with investigational (experimental) drug, CPX-351 and evaluate the efficacy of Palbociclib in combination with chemotherapy as measured by overall response rate (ORR), i.e. complete response (CR) and CR with incomplete blood count recovery (CRi) by 2003 IWG criteria.
Detailed description
The objectives of this study are to evaluate the safety and tolerability of Palbociclibin combination with CPX-351, and to evaluate the efficacy of Palbociclibin combination with chemotherapy as measured by overall response rate (ORR), i.e. complete response (CR) and CR with incomplete blood count recovery (CRi) by IWG criteria.
CPX-351 is an investigational drug that works as formulation of a fixed combination of the antineoplastic (acting to prevent, inhibit or halt the development of a neoplasm (a tumor)) drugs cytarabine and daunorubicin.
Palbociclibis an investigational drug that works to induce early G1 arrest by inhibiting CDK4/6, which are two types of CDKs that are overexpressed in AML cell cancer lines.
CPX-351 and Palbociclib is experimental because it is not approved by the Food and Drug Administration (FDA).
This is a single arm, open label study of the combination of Palbociclib with CPX-351 in adults with AML. The trial consists of two components: phase I to evaluate the safety with dose escalation of Palbociclib in combination with CPX-351 and phase II to evaluate the overall response rate of the combination in the targeted participant population.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a single arm, open label study of the combination of Palbociclib with CPX-351 in adults with AML. The trial consists of two components: phase I to evaluate the safety with dose escalation of Palbociclib in combination with CPX-351 and phase II to evaluate the overall response rate of the combination in the targeted patient population. A cycle is 28 days.
| Arm | Type | Receives |
|---|---|---|
| Palbociclib + CPX-351 | Experimental | Drug: Palcociclib, Drug: CPX-351Palbociclib will be administered orally on day -1 and -2 at 125 mg PO during the phase IIaportion (dose level 0).Day 0 will be rest and then CPX-351 at 100 u/m2 will be started on days 1, 3, and 5 along with Palbociclib day 2, 4, and 6 followed by rest/monitoring period (day 7-28). If Grade 3-4 non-hematologic toxicity is observed in 1 or less of 6 patients treated, the study will move to Phase IIb. If Grade 3-4 non-hematologic toxicity is observed in 2 or more of 6 patients treated, 6 additional patients will be treated on the Phase IIa portion at a lower dose level (100 mg po) until a Phase IIb safe dose schedule is defined at which 1 or less out of 6 patients on the Phase IIa experience Grade 3-4 non-hematologic toxicity. After the Phase IIa portion ensures safety, the study will proceed with phase IIb. The phase IIb component is a Simon 2-stage design trial whose objective is to assess the clinical efficacy of the combination of Palbociclib and CPX-351. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Newly diagnosed acute myeloid leukemia according to 2016 WHO criteria(excluding APL [AML-M3]).
- Eastern Cooperative Oncology Group (ECOG) Performance Status <2
- Subjects must have normal organ function as defined below:
- Total bilirubin <2 times upper limit of normal ((≤ 3 x ULN if considered to be due to leukemic involvement or Gilbert's syndrome) or if higher than 2 times upper limit of normal with approval from the PI
- Serum Creatinine <2 x ULNor if higher than 2 times upper limit of normal with approval from the PI
Key exclusion criteria (10 listed)
- Prior treatment with CPX-351, Palbociclib or other cell cycle inhibitors.
- Any serious medical condition, laboratory abnormality, or psychiatric illness that, in the view of the treating physician, would place the participant at an unacceptable risk if he or she were to participate in the study or would prevent that person from giving informed consent.
- Any active malignancy (unrelated, non-hematological malignancy) diagnosed within the past 6 months of starting the study drug (other than curatively treated carcinoma-in-situ of the cervix or non-melanoma skin cancer).
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to CPX-351, Palbociclib or other cell cycle inhibitors.
- Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
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 |
|---|---|---|
| PalcociclibAlso: IBRANCEPalbociclib is an investigational (experimental) drug that works to induce early G1 arrest by inhibiting CDK4/6, which are two types of CDKs that are overexpressed in AML cell cancer lines. Palbociclib is experimental because it is not approved by the Food and Drug Administration (FDA). Palbociclib will be supplied as capsules or tablets containing 125 mg equivalents of Palbociclib free base | Drug | Palbociclib + CPX-351 |
| CPX-351Also: VYXEOSCPX-351 (daunorubicin and cytarabine) liposome for injection is a combination of daunorubicin and cytarabine in a 1:5 molar ratio encapsulated in liposomes for intravenous administration. CPX-351 is an investigational (experimental) drug that works as formulation of a fixed combination of the antineoplastic drugs cytarabine and daunorubicin. CPX-351 is experimental because it is not approved by the Food and Drug Administration (FDA). | Drug | Palbociclib + CPX-351 |
Primary outcome
Safety and Tolerability of Experimental Dose of Palbociclibin Combination With CPX-351 as Measured by Number of Participants With Dose Limiting Toxicities.
Time frame: Between days 28-35 of starting treatment
If Grade 3-4 non-hematologic toxicity is observed in 1 or less of 6 patients treated, the dose of the study drug will be considered safe/tolerable. If Grade 3-4 non-hematologic toxicity is observed in 2 or more of 6 patients treated, 6 additional patients will be treated on the Phase IIa portion at a lower dose level (100 mg po).
Efficacy of Palbociclibin Combination With Chemotherapy as Measured by Overall Response Rate (ORR).
Time frame: Up to 2 years from end of treatment, up to 27 months
Efficacy of Palbociclibin combination with chemotherapy as measured by overall response rate (ORR) which is defined as complete response (CR) and CR with incomplete blood count recovery (CRi) by IWG criteria. Complete remission is defined as: Bone marrow blasts <5%; absence ofcirculating blasts and blasts with Auerrods; absence of extramedullarydisease; absolute neutrophil count >1.0x 109/L (1,000/μL); platelet count >100 x109/L (100,000/μL) and CR with incomplete blood count recovery is defined as: All CR criteria except for residualneutropenia [<1.0 x 109/L (1,000/μL)] orthrombocytopenia [<100 x 109/L(100,000/μL)]. Either of these responses will constitute ORR.
4 secondary outcomes
Time to Response (TTR)
Time frame: Up to 2 years from end of treatment
Duration of Response (DOR)
Time frame: Up to 2 years from end of treatment
Event-free Survival (EFS)
Time frame: Up to 2 years from end of treatment
Overall Survival (OS) Probability
Time frame: Up to 2 years from end of treatment, up to 27 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Sudipto Mukherjee, MD, PhD principal investigator
Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Palcociclib and CPX-351 in people with Acute Myeloid Leukemia and AML, run by Sudipto Mukherjee, MD, PhD, MPH at 1 site 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 9 inclusion and 10 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: finished, as of the sponsor's last update on 31 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Yes. Results are posted in the registry (first posted 31 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Safety and Tolerability of Experimental Dose of Palbociclibin Combination With CPX-351 as Measured by Number of Participants With Dose Limiting Toxicities. (time frame: Between days 28-35 of starting treatment). The study lists 2 primary outcomes in all. 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 31 May 2025.