CPX-351 Therapy for MDS After Hypomethylating Agent Failure

NCT03957876 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: CASE2918
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the efficacy of treatment with CPX-351 (an FDA approved drug for the treatment of AML) in individuals with MDS while using a new stratification tool to predict outcomes of participants following HMA failure. This approach is intended to gain a better understanding and insight into identifying new opportunities for drug approvals in this setting.

Conditions

Myelodysplastic Syndrome (MDS)

Outcome Measures

Primary Outcomes (1)

• Efficacy of CPX-351 as Measured by Overall Response Rate (ORR)

  Efficacy of CPX as measured by ORR as defined by IWG 2006 criteria for MDS participants at end of induction. IWG 2006 responses that must be for at least 4 weeks include Complete Remission (CR), Partial Remission (PR), Marrow CR, Stable Disease (SD), Failure, Relapse after CR or PR (PD), or cytogenetic response. Hematologic Improvement (HI), which must be for at least 8 weeks, includes erythroid response (pretreatment, \< 11 g/dL), Platelet response (pretreatment, \< 100x109/L), Neutrophil response (pretreatment, \< 1 x109/L), or Progression or relapse after HI.

  day 28 +/- 7 days of induction

Secondary Outcomes (4)

• Time to Response (TTR) Associated With CPX-351

  day 28 +/- 7 days of induction

• Duration of Response (DOR) in Participants Achieving a Response

  up to 1 year after end of treatment

• Event-free Survival (EFS)

  up to 1 year after end of treatment

• Overall Survival (OS)

  up to 1 year after end of treatment

Study Arms (1)

intravenous CPX-351 with potential maintenance therapy

EXPERIMENTAL

Single agent CPX-351 administered at the standard FDA approved dose of 44 mg/m2 intravenously on days 1, 3, 5 of the induction cycle. If participants achieve complete remission (CR), complete remission with incomplete count recovery (CRi) or partial remission (PR), they will be eligible to continue on to maintenance therapy, which will consist of CPX351 at a dose of 15.4 mg/m2 every 28 days. Participants can receive up to 4 cycles of maintenance therapy.

Drug: CPX-351

Interventions

CPX-351 DRUG

CPX-351 is a liposomal formulation of a fixed combination of the antineoplastic drugs cytarabine and daunorubicin.

Also known as: (daunorubicin and cytarabine)

intravenous CPX-351 with potential maintenance therapy

Eligibility Criteria

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

You may qualify if:

• Patients must give voluntary written consent before performance of any study related procedures not part of standard medical care
• Diagnosis of MDS or MDS/MPN according to 2016 WHO criteria12
• Primary therapy failure with either hypomethylating agents (decitabine or azacitidine) defined as:
• Progression (according to 2006 IWG criteria)13 after initiation of azacitidine or decitabine treatment; or
• Failure to achieve complete or partial response or hematological improvement (according to 2006 IWG)13 after at least 4-6 cycles (4-weeks cycle) of azacitidine or decitabine; or
• Relapse after initial complete or partial response or hematological improvement (according to 2006 IWG criteria)13 observed after at least 4 cycles of azacitidine or decitabine.
• Eastern Cooperative Oncology Group (ECOG) Performance Status \< 2
• Subjects must have normal organ and marrow function defined as:
• If total bilirubin \< 2x upper limit of normal (\</= 3 x ULN if considered to be due to leukemic involvement or Gilbert's syndrome) at the discretion of the treating physician following discussion with PI)
• Calculated creatinine clearance value of \> 30ml/min AND a serum creatinine \< 1.5mg/dL
• LVEF \>/= 50%
• Female patients who:
• Are postmenopausal for at least 1 year before the screening visit, OR
• Are surgically sterile, OR
• Agree to practice true abstinence from heterosexual contact or agree to use effective contraception without interruption during the study therapy and 90 days after the last dose

You may not qualify if:

• Prior treatment with CPX-351, or known hypersensitivity to CPX-351 or its components.
• Prior treatment with intensive chemotherapy.
• 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).
• Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Known history of HIV or active hepatitis B or C.
• Major surgery within 2 weeks prior to study enrollment.
• Pregnant or lactating females
• Male and female patients who are fertile who do not agree to use an effective barrier methods of birth control (i.e. abstinence or 2 forms of contraception) to avoid pregnancy while receiving study treatment.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

CPX-351; Daunorubicin; Cytarabine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Limitations and Caveats

Early termination led to a small number of subjects analyzed.

Results Point of Contact

• Title: Sudipto Mukherjee, MD, PhD, MPH
• Organization: Cleveland Clinic Foundation, Case Comprehensive Cancer Center

mukhers2@ccf.org

216-444-0506

Study Officials

• Sudipto Mukherjee, MD, PhD

  Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 10, 2019
• First Posted: May 21, 2019
• Study Start: July 25, 2019
• Primary Completion: December 20, 2022
• Study Completion: December 20, 2022
• Last Updated: August 15, 2024
• Results First Posted: August 15, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)