Brief Title
CPX-351 as a Novel Approach for the Treatment of Older Patients With AML and MDS
Official Title
Lower Doses of CPX-351 as a Novel Approach for the Treatment of Older Patients With Relapsed or Refractory Acute Myeloid Leukemia and Myelodysplastic Syndromes
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.
Detailed Description
Currently, elderly patients with AML and high risk MDS, who are ineligible to receive
induction chemotherapy and fail HMA +/- combination, have very poor outcomes and there is no
FDA-approved therapy outside of some targeted therapies which can only be applied to a small
patient population. CPX-351 is an investigational (experimental) drug that works by combining
two anti-cancer drugs cytarabine and daunorubicin. CPX-351 is experimental because it is only
FDA approved for the treatment of adults with two types of AML: newly diagnosed
therapy-related AML or AML with myelodysplasia-related changes.
This is an open label clinical trial of lower doses of CPX-351 in relapsed/primary refractory
older AML and MDS patients ineligible to receive intensive chemotherapy. The first arm is for
particpants with primary refractory/relapsed AML and the second arm is for higher risk MDS
participants after HMA failure.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Overall response rate (ORR) per 2003 International Working Group (IWG) criteria
Secondary Outcome
Time to response (TTR)
Condition
Refractory Acute Myeloid Leukemia
Intervention
CPX-351
Study Arms / Comparison Groups
Primary refractory/relapsed AML
Description: Lower dose CPX-351 in participants with primary refractory/relapsed AML. Participants will receive an induction and maintenance phase of CPX-351
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
13
Start Date
January 14, 2021
Completion Date
December 2025
Primary Completion Date
December 2023
Eligibility Criteria
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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)
Gender
All
Ages
60 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Sudipto Mukherjee, MD, PhD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT04668885
Organization ID
CASE1920
Responsible Party
Sponsor
Study Sponsor
Case Comprehensive Cancer Center
Study Sponsor
Sudipto Mukherjee, MD, PhD, Principal Investigator, Cleveland Clinic, Case Comprehensive Cancer Center
Verification Date
November 2022