Back to resultsPhase I/II Trial of CPX-351 + Palbociclib in Patients With Acute Myeloid Leukemia
Primary Purpose
Acute Myeloid Leukemia, AML
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Palcociclib
CPX-351
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia
Eligibility Criteria
Inclusion Criteria:
- 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%
- 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.
Exclusion Criteria:
- 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.
- 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)
Sites / Locations
- Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Palbociclib + CPX-351
Arm Description
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.
Outcomes
Primary Outcome Measures
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).
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.
Secondary Outcome Measures
Time to response (TTR)
TTR measured between start of treatment and the date of achievement of response (responses defined per 2003 IWG criteria).
Duration of response (DOR)
DOR is measured between the date of response to date of loss of response.
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
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03844997
Brief Title
Phase I/II Trial of CPX-351 + Palbociclib in Patients With Acute Myeloid Leukemia
Official Title
Phase I/II Trial of CPX-351 + Palbociclib in Patients With Acute Myeloid Leukemia
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
June 6, 2019 (Actual)
Primary Completion Date
June 2023 (Anticipated)
Study Completion Date
June 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Sudipto Mukherjee
4. Oversight
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.
Yes
Data Monitoring Committee
Yes
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia, AML
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
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)
Allocation
N/A
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Palbociclib + CPX-351
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Palcociclib
Other Intervention Name(s)
IBRANCE
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
CPX-351
Other Intervention Name(s)
VYXEOS
Intervention Description
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).
Primary Outcome Measure Information:
Title
Safety and tolerability of experimental dose of Palbociclibin combination with CPX-351 as measured by number of participants with dose limiting toxicities.
Description
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).
Time Frame
Between days 28-35 of starting treatment
Title
Efficacy of Palbociclibin combination with chemotherapy as measured by overall response rate (ORR).
Description
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.
Time Frame
Up to 2 years from end of treatment
Secondary Outcome Measure Information:
Title
Time to response (TTR)
Description
TTR measured between start of treatment and the date of achievement of response (responses defined per 2003 IWG criteria).
Time Frame
Up to 2 years from end of treatment
Title
Duration of response (DOR)
Description
DOR is measured between the date of response to date of loss of response.
Time Frame
Up to 2 years from end of treatment
Title
Event-free survival (EFS)
Description
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
Time Frame
Up to 2 years from end of treatment
Title
Overall Survival (OS) probability
Description
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
Time Frame
Up to 2 years from end of treatment
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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%
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.
Exclusion Criteria:
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.
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sudipto Mukherjee, MD, PhD
Organizational Affiliation
Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Phase I/II Trial of CPX-351 + Palbociclib in Patients With Acute Myeloid Leukemia
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