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Phase IB/II of CPX-351 for Relapse Prevention in AML

Primary Purpose

Acute Myeloid Leukemia (AML) in Remission

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CPX-351
Sponsored by
Georgetown University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia (AML) in Remission focused on measuring Acute Myeloid Leukemia, Remission

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Newly diagnosed patients > 18 years of age
  • Patients must be in CR or CRh (complete remission with partial count recovery).
  • Must have received ANY induction treatment with standard consolidation or hypomethylating agent (HMA) + venetoclax, for up to 6 cycles or no more than one year of treatment.
  • Must be able to start therapy within 3 months of last documented CR
  • De novo or secondary AML/treatment related AML (non-M3) including AML with myelodysplasia-related changes (MRC), histologically confirmed
  • Patients must be ineligible for allogeneic BMT (for any reason including poor performance status, patient's preference, favorable AML not a candidate for transplant, or comorbidities and age precluding from transplant etc)
  • Cardiac ejection fraction ≥ 50% by transthoracic echocardiography or MUGA scan
  • Adequate hepatic and renal function defined as:

    • Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 3 x upper limit of normal (ULN)
    • Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 3 is permissible if due to disease.
    • Bilirubin ≤3 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin)
    • Estimated Creatinine Clearance ≥30 ml/min (Cockcroft-Gault based on actual weight) (See Appendix A)
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 3 (Appendix A)
  • Female subjects who are of non-reproductive potential (i.e., post-menopausal by history - no menses for ≥1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Female subjects of childbearing potential must have a negative serum pregnancy test upon study entry.
  • Male and female subjects who agree to use highly effective methods of birth control (e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], sexual abstinence, or sterilized partner) during the period of therapy and for at least 6 months after the last dose of study drug

Exclusion Criteria:

  • Prior allogeneic transplant
  • Previous cumulative anthracycline (doxorubicin equivalent) dose equal to or greater than 345 mg/m2, and for patients with prior mediastinal XRT, anthracycline dose equal to or greater than 295 mg/m2
  • Acute promyelocytic leukemia [t(15;17)]
  • If patient is unable to sign informed consent due to any serious medical condition, laboratory abnormality or psychiatric illness
  • Patients with evidence of uncontrolled current myocardial impairment (e.g. unstable ischemic heart disease, uncontrolled arrhythmia, symptomatic valvular dysfunction not controlled on medical therapy, uncontrolled hypertensive heart disease, and uncontrolled congestive heart failure)
  • History of Wilson's disease or other copper-related disorders
  • History of allergic reactions attributed to compounds of similar composition to cytarabine and daunorubicin or liposomal products
  • History of other malignancies, except:

    • Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician.
    • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
    • Adequately treated carcinoma in situ without evidence of disease.
  • Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 4.03), grade ≤1, or to the levels dictated in the inclusion/exclusion criteria with the exception of alopecia.
  • Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia
  • Known active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV).
  • Subjects who are positive for hepatitis B core antibody, hepatitis B surface antigen, hepatitis C antibody, must have a negative polymerase chain reaction (PCR) result for the respective disease before enrollment. Those who are PCR positive will be excluded.
  • Any uncontrolled active systemic infection.
  • Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk.
  • Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization.
  • Known CNS involvement by leukemia
  • Erythema multiforme, toxic epidermal necrolysis, or Stevens-Johnson syndrome
  • Lactating or pregnant.
  • Unwilling or unable to participate in all required study evaluations and procedures.
  • Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations).
  • Currently active, clinically significant hepatic impairment (≥ moderate hepatic impairment according to the Child Pugh classification (class B or C))

Sites / Locations

  • Georgetown Lombardi Comprehensive Cancer CenterRecruiting
  • John Theurer Cancer Center at Hackensack University Medical CenterRecruiting
  • University of PennsylvaniaRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

CPX-351

Arm Description

Dose Level 1: CPX-351 administered through intravenou infusion on Day 1 and Day 3 of 28 day cycle for 6 cycles or Dose Level -1: CPX-351 administered through intravenous infusion on Day 1 of each 28 day cycle for 6 cycles.

Outcomes

Primary Outcome Measures

Maximum tolerate dose (Phase 1)
Number of subjects with Dose Limiting toxicities will be used to determine the recommended phase II dose of CPX-351 to be used in the maintenance setting for newly diagnosed AML in complete remission.
Inicidence of Treatment Emergent Adverse events (Phase 2)
To determine the safety, tolerability and toxicity of CPX-351 in the maintenance setting for newly diagnosed AML in complete remission by analyzing the incidence of treatment emergent adverse events reported.

Secondary Outcome Measures

Incidence of Treatment Emergent Adverse Events (Phase 1)
To determine the safety, tolerability and toxicity of CPX-351 in the maintenance setting for newly diagnosed AML in complete remission by analyzing the incidence of treatment emergent adverse events reported.
Overall Survival (Phase 1 and 2)
Determine the efficacy of CPX-351 as maintenance treatment in newly diagnosed AML patients who have achieved remission after induction treatment as measured by overall survival of subjects.
Event free survival (Phase 1 and 2)
Determine efficacy of CPX-351 as maintenance treatment in newly diagnosed AML patients who have achieved remission after induction treatment as measured by event free survival.
Relapse Free Survival (Phase 1 and 2)
Determine efficacy of CPX-351 as maintenance treatment in newly diagnosed AML patients who have achieved remission after induction treatment as measured by relapse free survival.

Full Information

First Posted
July 26, 2021
Last Updated
September 11, 2023
Sponsor
Georgetown University
Collaborators
Jazz Pharmaceuticals, National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT04990102
Brief Title
Phase IB/II of CPX-351 for Relapse Prevention in AML
Official Title
Phase IB/II of CPX-351 as Maintenance Therapy in AML Patients Ineligible for Bone Marrow Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 22, 2023 (Actual)
Primary Completion Date
August 2024 (Anticipated)
Study Completion Date
August 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Georgetown University
Collaborators
Jazz Pharmaceuticals, National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This is a phase IB/II study with a 3+3 dose de-escalation study design. Patients will continue maintenance treatment with CPX-351 for 6 cycles on D1 and D3, as long as patient remains in CR. The dose de-escalation will be one dose given on D1 only, every 28 days pending toxicity. The maximum tolerated dose will be used for the phase II expansion portion of the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia (AML) in Remission
Keywords
Acute Myeloid Leukemia, Remission

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
Dose de-escalation of CPX-351
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CPX-351
Arm Type
Experimental
Arm Description
Dose Level 1: CPX-351 administered through intravenou infusion on Day 1 and Day 3 of 28 day cycle for 6 cycles or Dose Level -1: CPX-351 administered through intravenous infusion on Day 1 of each 28 day cycle for 6 cycles.
Intervention Type
Drug
Intervention Name(s)
CPX-351
Other Intervention Name(s)
Vyxeos
Intervention Description
Daunorubicin 8.8mg/m2 + cytarabine 20mg/m2
Primary Outcome Measure Information:
Title
Maximum tolerate dose (Phase 1)
Description
Number of subjects with Dose Limiting toxicities will be used to determine the recommended phase II dose of CPX-351 to be used in the maintenance setting for newly diagnosed AML in complete remission.
Time Frame
1 cycle (28 day cycle)
Title
Inicidence of Treatment Emergent Adverse events (Phase 2)
Description
To determine the safety, tolerability and toxicity of CPX-351 in the maintenance setting for newly diagnosed AML in complete remission by analyzing the incidence of treatment emergent adverse events reported.
Time Frame
6 cycles (28 day cycles)
Secondary Outcome Measure Information:
Title
Incidence of Treatment Emergent Adverse Events (Phase 1)
Description
To determine the safety, tolerability and toxicity of CPX-351 in the maintenance setting for newly diagnosed AML in complete remission by analyzing the incidence of treatment emergent adverse events reported.
Time Frame
6 cycles (28 day Cycle)
Title
Overall Survival (Phase 1 and 2)
Description
Determine the efficacy of CPX-351 as maintenance treatment in newly diagnosed AML patients who have achieved remission after induction treatment as measured by overall survival of subjects.
Time Frame
1 year after end of treatment
Title
Event free survival (Phase 1 and 2)
Description
Determine efficacy of CPX-351 as maintenance treatment in newly diagnosed AML patients who have achieved remission after induction treatment as measured by event free survival.
Time Frame
1 year after end of treatment
Title
Relapse Free Survival (Phase 1 and 2)
Description
Determine efficacy of CPX-351 as maintenance treatment in newly diagnosed AML patients who have achieved remission after induction treatment as measured by relapse free survival.
Time Frame
1 year after end of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Newly diagnosed patients > 18 years of age Patients must be in CR or CRh (complete remission with partial count recovery). Must have received ANY induction treatment with standard consolidation or hypomethylating agent (HMA) + venetoclax, for up to 6 cycles or no more than one year of treatment. Must be able to start therapy within 3 months of last documented CR De novo or secondary AML/treatment related AML (non-M3) including AML with myelodysplasia-related changes (MRC), histologically confirmed Patients must be ineligible for allogeneic BMT (for any reason including poor performance status, patient's preference, favorable AML not a candidate for transplant, or comorbidities and age precluding from transplant etc) Cardiac ejection fraction ≥ 50% by transthoracic echocardiography or MUGA scan Adequate hepatic and renal function defined as: Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 3 x upper limit of normal (ULN) Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 3 is permissible if due to disease. Bilirubin ≤3 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin) Estimated Creatinine Clearance ≥30 ml/min (Cockcroft-Gault based on actual weight) (See Appendix A) Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 3 (Appendix A) Female subjects who are of non-reproductive potential (i.e., post-menopausal by history - no menses for ≥1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Female subjects of childbearing potential must have a negative serum pregnancy test upon study entry. Male and female subjects who agree to use highly effective methods of birth control (e.g., condoms, implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], sexual abstinence, or sterilized partner) during the period of therapy and for at least 6 months after the last dose of study drug Exclusion Criteria: Prior allogeneic transplant Previous cumulative anthracycline (doxorubicin equivalent) dose equal to or greater than 345 mg/m2, and for patients with prior mediastinal XRT, anthracycline dose equal to or greater than 295 mg/m2 Acute promyelocytic leukemia [t(15;17)] If patient is unable to sign informed consent due to any serious medical condition, laboratory abnormality or psychiatric illness Patients with evidence of uncontrolled current myocardial impairment (e.g. unstable ischemic heart disease, uncontrolled arrhythmia, symptomatic valvular dysfunction not controlled on medical therapy, uncontrolled hypertensive heart disease, and uncontrolled congestive heart failure) History of Wilson's disease or other copper-related disorders History of allergic reactions attributed to compounds of similar composition to cytarabine and daunorubicin or liposomal products History of other malignancies, except: Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician. Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. Adequately treated carcinoma in situ without evidence of disease. Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 4.03), grade ≤1, or to the levels dictated in the inclusion/exclusion criteria with the exception of alopecia. Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia Known active infection with hepatitis C virus (HCV) or hepatitis B virus (HBV). Subjects who are positive for hepatitis B core antibody, hepatitis B surface antigen, hepatitis C antibody, must have a negative polymerase chain reaction (PCR) result for the respective disease before enrollment. Those who are PCR positive will be excluded. Any uncontrolled active systemic infection. Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk. Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization. Known CNS involvement by leukemia Erythema multiforme, toxic epidermal necrolysis, or Stevens-Johnson syndrome Lactating or pregnant. Unwilling or unable to participate in all required study evaluations and procedures. Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations). Currently active, clinically significant hepatic impairment (≥ moderate hepatic impairment according to the Child Pugh classification (class B or C))
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kimberley Doucette, MD
Organizational Affiliation
Georgetown University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Georgetown Lombardi Comprehensive Cancer Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thomas White
Phone
202-687-9194
Email
thomas.white@georgetown.edu
First Name & Middle Initial & Last Name & Degree
Kimberley Doucette, MD
Facility Name
John Theurer Cancer Center at Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lumi Demirovic
Phone
551-996-8154
Email
Ljumnije.demirovic@hmhn.org
First Name & Middle Initial & Last Name & Degree
James McCloskey, MD
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ashlena Livingston
Phone
215-519-1180
Email
Ashlena.Livingston@pennmedicine.upenn.edu
First Name & Middle Initial & Last Name & Degree
Catherine Lai, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Phase IB/II of CPX-351 for Relapse Prevention in AML

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