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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Time to response (TTR) | TTR is measured from start of treatment to the date of achieving a response. Wilcoxon rank test will be used for comparison of continuous variables. | At 6 months |
| Time to response (TTR) |
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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:
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:
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| Name | Affiliation | Role |
|---|---|---|
| Sudipto Mukherjee, MD, PhD | Cleveland Clinic, Case Comprehensive Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cleveland Clinic, Case Comprehensive Cancer Center | Cleveland | Ohio | 44106-5065 | United States |
There are no plans to share individual patient data in order to protect the confidentiality of the participants who enroll on this study
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| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| D015479 | Leukemia, Myelomonocytic, Acute |
| D009190 | Myelodysplastic Syndromes |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| C000629812 | CPX-351 |
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|
| 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 |
TTR is measured from start of treatment to the date of achieving a response. Wilcoxon rank test will be used for comparison of continuous variables.
| At 1 year |
| Time to response (TTR) | TTR is measured from start of treatment to the date of achieving a response. Wilcoxon rank test will be used for comparison of continuous variables. | At 1.5 years |
| Time to response (TTR) | TTR is measured from start of treatment to the date of achieving a response. Wilcoxon rank test will be used for comparison of continuous variables. | At 2 years |
| Time to response (TTR) | TTR is measured from start of treatment to the date of achieving a response. Wilcoxon rank test will be used for comparison of continuous variables. | At 2.5 years |
| Time to response (TTR) | TTR is measured from start of treatment to the date of achieving a response. Wilcoxon rank test will be used for comparison of continuous variables. | At 3 years |
| Time to response (TTR) | TTR is measured from start of treatment to the date of achieving a response. Wilcoxon rank test will be used for comparison of continuous variables. | At 3.5 years |
| Time to response (TTR) | TTR is measured from start of treatment to the date of achieving a response. Wilcoxon rank test will be used for comparison of continuous variables. | At 4 years |
| Time to response (TTR) | TTR is measured from start of treatment to the date of achieving a response. Wilcoxon rank test will be used for comparison of continuous variables. | At 4.5 years |
| Time to response (TTR) | TTR is measured from start of treatment to the date of achieving a response. Wilcoxon rank test will be used for comparison of continuous variables. | At 5 years |
| Duration of response (DOR) | DOR measured from the time of achieving a response to time of disease progression. Wilcoxon rank test will be used for comparison of continuous variables. | At 6 months |
| Duration of response (DOR) | DOR measured from the time of achieving a response to time of disease progression. Wilcoxon rank test will be used for comparison of continuous variables. | At 1 year |
| Duration of response (DOR) | DOR measured from the time of achieving a response to time of disease progression. Wilcoxon rank test will be used for comparison of continuous variables. | At 1.5 years |
| Duration of response (DOR) | DOR measured from the time of achieving a response to time of disease progression. Wilcoxon rank test will be used for comparison of continuous variables. | At 2 years |
| Duration of response (DOR) | DOR measured from the time of achieving a response to time of disease progression. Wilcoxon rank test will be used for comparison of continuous variables. | At 2.5 years |
| Duration of response (DOR) | DOR measured from the time of achieving a response to time of disease progression. Wilcoxon rank test will be used for comparison of continuous variables. | At 3 years |
| Duration of response (DOR) | DOR measured from the time of achieving a response to time of disease progression. Wilcoxon rank test will be used for comparison of continuous variables. | At 3.5 years |
| Duration of response (DOR) | DOR measured from the time of achieving a response to time of disease progression. Wilcoxon rank test will be used for comparison of continuous variables. | At 4 years |
| Duration of response (DOR) | DOR measured from the time of achieving a response to time of disease progression. Wilcoxon rank test will be used for comparison of continuous variables. | At 4.5 years |
| Duration of response (DOR) | DOR measured from the time of achieving a response to time of disease progression. Wilcoxon rank test will be used for comparison of continuous variables. | At 5 years |
| Event-free survival (EFS) | EFS measured from date of first dose to the date of treatment failure, relapse, or death from any cause. Wilcoxon rank test will be used for comparison of continuous variables | At 6 months |
| Event-free survival (EFS) | EFS measured from date of first dose to the date of treatment failure, relapse, or death from any cause. Wilcoxon rank test will be used for comparison of continuous variables | At 1 year |
| Event-free survival (EFS) | EFS measured from date of first dose to the date of treatment failure, relapse, or death from any cause. Wilcoxon rank test will be used for comparison of continuous variables | At 1.5 years |
| Event-free survival (EFS) | EFS measured from date of first dose to the date of treatment failure, relapse, or death from any cause. Wilcoxon rank test will be used for comparison of continuous variables | At 2 years |
| Event-free survival (EFS) | EFS measured from date of first dose to the date of treatment failure, relapse, or death from any cause. Wilcoxon rank test will be used for comparison of continuous variables | At 2.5 years |
| Event-free survival (EFS) | EFS measured from date of first dose to the date of treatment failure, relapse, or death from any cause. Wilcoxon rank test will be used for comparison of continuous variables | At 3 years |
| Event-free survival (EFS) | EFS measured from date of first dose to the date of treatment failure, relapse, or death from any cause. Wilcoxon rank test will be used for comparison of continuous variables | At 3.5 years |
| Event-free survival (EFS) | EFS measured from date of first dose to the date of treatment failure, relapse, or death from any cause. Wilcoxon rank test will be used for comparison of continuous variables | At 4 years |
| Event-free survival (EFS) | EFS measured from date of first dose to the date of treatment failure, relapse, or death from any cause. Wilcoxon rank test will be used for comparison of continuous variables | At 4.5 years |
| Event-free survival (EFS) | EFS measured from date of first dose to the date of treatment failure, relapse, or death from any cause. Wilcoxon rank test will be used for comparison of continuous variables | At 5 years |
| Overall Survival (OS) | OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method | At 6 months |
| Overall Survival (OS) | OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method | At 1 year |
| Overall Survival (OS) | OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method | At 1.5 years |
| Overall Survival (OS) | OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method | At 2 years |
| Overall Survival (OS) | OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method | At 2.5 years |
| Overall Survival (OS) | OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method | At 3 years |
| Overall Survival (OS) | OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method | At 3.5 years |
| Overall Survival (OS) | OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method | At 4 years |
| Overall Survival (OS) | OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method | At 4.5 years |
| Overall Survival (OS) | OS measured from start of treatment to death or last follow up. OS function will be estimated using the Kaplan-Meier method | At 5 years |
| D006402 |
| Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D001855 | Bone Marrow Diseases |