CPX-351 as a Novel Approach for the Treatment of Older Patients With AML and MDS

NCT04668885 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CASE1920
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate how effective lower doses of CPX-351 are in older participants with relapsed/refractory acute myeloid leukemia (AML) who are not eligible to receive intensive chemotherapy and in participants with myelodysplastic syndromes (MDS) after Hypomethylating Agents (HMA) failure.

Conditions

Refractory Acute Myeloid Leukemia; Relapsed Acute Myelomonocytic Leukemia; Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (10)

• Overall response rate (ORR) per 2003 International Working Group (IWG) criteria

  ORR = complete response (CR) + CR with incomplete blood count recovery (CRi) + partial remission (PR) as defined by 2003 IWG criteria for AML patients, and ORR = CR + PR + hematologic improvement (HI) and as defined per 2006 IWG criteria for MDS patients

  At 6 months

• Overall response rate (ORR) per 2003 IWG criteria

  ORR = complete response (CR) + CR with incomplete blood count recovery (CRi) + partial remission (PR) as defined by 2003 IWG criteria for AML patients, and ORR = CR + PR + hematologic improvement (HI) and as defined per 2006 IWG criteria for MDS patients

  At 1 year

• Overall response rate (ORR) per 2003 IWG criteria

  ORR = complete response (CR) + CR with incomplete blood count recovery (CRi) + partial remission (PR) as defined by 2003 IWG criteria for AML patients, and ORR = CR + PR + hematologic improvement (HI) and as defined per 2006 IWG criteria for MDS patients

  At 1.5 years

• Overall response rate (ORR) per 2003 IWG criteria

  ORR = complete response (CR) + CR with incomplete blood count recovery (CRi) + partial remission (PR) as defined by 2003 IWG criteria for AML patients, and ORR = CR + PR + hematologic improvement (HI) and as defined per 2006 IWG criteria for MDS patients

  At 2 years

• Overall response rate (ORR) per 2003 IWG criteria

  ORR = complete response (CR) + CR with incomplete blood count recovery (CRi) + partial remission (PR) as defined by 2003 IWG criteria for AML patients, and ORR = CR + PR + hematologic improvement (HI) and as defined per 2006 IWG criteria for MDS patients

  At 2.5 years

• Overall response rate (ORR) per 2003 IWG criteria

  ORR = complete response (CR) + CR with incomplete blood count recovery (CRi) + partial remission (PR) as defined by 2003 IWG criteria for AML patients, and ORR = CR + PR + hematologic improvement (HI) and as defined per 2006 IWG criteria for MDS patients

  At 3 years

• Overall response rate (ORR) per 2003 IWG criteria

  ORR = complete response (CR) + CR with incomplete blood count recovery (CRi) + partial remission (PR) as defined by 2003 IWG criteria for AML patients, and ORR = CR + PR + hematologic improvement (HI) and as defined per 2006 IWG criteria for MDS patients

  At 3.5 years

• Overall response rate (ORR) per 2003 IWG criteria

  ORR = complete response (CR) + CR with incomplete blood count recovery (CRi) + partial remission (PR) as defined by 2003 IWG criteria for AML patients, and ORR = CR + PR + hematologic improvement (HI) and as defined per 2006 IWG criteria for MDS patients

  At 4 years

• Overall response rate (ORR) per 2003 IWG criteria

  ORR = complete response (CR) + CR with incomplete blood count recovery (CRi) + partial remission (PR) as defined by 2003 IWG criteria for AML patients, and ORR = CR + PR + hematologic improvement (HI) and as defined per 2006 IWG criteria for MDS patients

  At 4.5 years

• Overall response rate (ORR) per 2003 IWG criteria

  ORR = complete response (CR) + CR with incomplete blood count recovery (CRi) + partial remission (PR) as defined by 2003 IWG criteria for AML patients, and ORR = CR + PR + hematologic improvement (HI) and as defined per 2006 IWG criteria for MDS patients

  At 5 years

Secondary Outcomes (40)

• Time to response (TTR)

  At 6 months

• Time to response (TTR)

  At 1 year

• Time to response (TTR)

  At 1.5 years

• Time to response (TTR)

  At 2 years

• Time to response (TTR)

  At 2.5 years

Study Arms (2)

Primary refractory/relapsed AML

EXPERIMENTAL

Lower dose CPX-351 in participants with primary refractory/relapsed AML. Participants will receive an induction and maintenance phase of CPX-351

Drug: CPX-351

MDS after HMA failure

EXPERIMENTAL

Lower dose CPX-351 in participants with MDS after HMA failure. Participants will receive an induction and maintenance phase of CPX-351

Drug: CPX-351

Interventions

CPX-351 DRUG

Induction phase: CPX-351 15 mg/m\^2 on days 1 and 3 of each 28-day cycle for up to a total of 6 cycles in the absence of unacceptable toxicity Maintenance phase: CPX-351 7.5 mg/m\^2 on days 1 and 3 for two cycles alternating with 15 mg/m\^2 for one cycle. Participants may receive up to 12 cycles of maintenance phase in the absence of unacceptable toxicity.

MDS after HMA failure; Primary refractory/relapsed AML

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Primary refractory or relapsed AML (defined by 2016 World Health Organization \[WHO\] criteria) patients who are not suitable for or not willing to receive intensive chemotherapy as evaluated by the treating physician. Primary refractory disease is defined as:
• Failure to achieve a CR, CRi, or mLFS (defined as \<5% Bone Marrow (BM) blasts) after receiving 1 or 2 cycles of remission induction chemotherapy.
• Failure to achieve a CR, CRi, or MLFS (defined as \<5% BM blasts) after receiving 4 cycles of non-intensive chemotherapy or whose disease progressed at any time point during the treatment.
• Participants with MDS (according to 2016 WHO criteria) who did not respond to treatment with azacitidine, decitabine, or combination of HMA with another drug or lost their response to initial therapy with HMA.
• Eastern Cooperative Oncology Group (ECOG) performance status \<=2
• Adequate hepatic (serum total bilirubin \< 1.5 x ULN, Serum glutamic pyruvic transaminase (SGPT) and/or serum glutamate oxaloacetate transaminase (SGOT) \<2.5 x ULN) and renal function (creatinine \< 1.5mg/dL).
• Participants must be willing and able to review, understand, and provide written consent before starting therapy.

You may not qualify if:

• Active signs or symptoms of central nervous system (CNS) involvement by malignancy (lumbar puncture \[LP\] not required).
• Prior 7+3 remission induction chemotherapy for MDS or AML
• More than 2 lines of prior non-intensive therapy.
• New York Heart Association (NYHA) class III or IV heart disease, active ischemia or any other uncontrolled cardiac condition such as angina pectoris, clinically significant cardiac arrhythmia on rhythm control strategy or on pacemaker, uncontrolled hypertension (blood pressure \> 160 systolic and \> 110 diastolic not responsive to antihypertensive medication)
• Acute myocardial infarction in the previous 12 weeks (from the start of treatment).
• 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.
• 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.
• Pregnant or breast feeding
• Male and female participants 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 and for 30 days after last dose of study treatment. Non-childbearing is defined as \> 1 year postmenopausal or surgically sterilized.
• Acute promyelocytic leukemia (APL)

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

Cleveland Clinic, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Myelodysplastic Syndromes

Interventions

CPX-351

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Officials

• Sudipto Mukherjee, MD, PhD

  Cleveland Clinic, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2020
• First Posted: December 16, 2020
• Study Start: January 14, 2021
• Primary Completion: October 10, 2025
• Study Completion (Estimated): October 10, 2026
• Last Updated: July 15, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)