Description:
This phase I trial studies best dose and side effects of liposome-encapsulated
daunorubicin-cytarabine (CPX-351) and how well it works in treating patients with high risk
myelodysplastic syndrome or chronic myelomonocytic leukemia that has come back or has not
responded to treatment. Drugs used in chemotherapy, such as liposome-encapsulated
daunorubicin-cytarabine, work in different ways to stop the growth of cancer cells, either by
killing the cells, by stopping them from dividing, or by stopping them from spreading.
Title
- Brief Title: CPX-351 in Treating Patients With Relapsed or Refractory High Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia
- Official Title: Phase 1 Dose Escalation Study of CPX-351 for Patients With Int-2 or High Risk IPSS Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia After Failure to Hypomethylating Agents
Clinical Trial IDs
- ORG STUDY ID:
2018-0911
- SECONDARY ID:
NCI-2019-01558
- SECONDARY ID:
2018-0911
- SECONDARY ID:
P30CA016672
- NCT ID:
NCT03896269
Conditions
- Blasts 10-19 Percent of Bone Marrow Nucleated Cells
- Blasts More Than 5 Percent of Bone Marrow Nucleated Cells
- High Risk Chronic Myelomonocytic Leukemia
- Recurrent Chronic Myelomonocytic Leukemia
- Recurrent High Risk Myelodysplastic Syndrome
- Refractory Chronic Myelomonocytic Leukemia
- Refractory High Risk Myelodysplastic Syndrome
Interventions
Drug | Synonyms | Arms |
---|
Liposome-encapsulated Daunorubicin-Cytarabine | CPX-351, Cytarabine-Daunorubicin Liposome for Injection, Liposomal AraC-Daunorubicin CPX-351, Liposomal Cytarabine-Daunorubicin, Liposome-encapsulated Combination of Daunorubicin and Cytarabine, Vyxeos | Treatment (liposome-encapsulated daunorubicin-cytarabine) |
Purpose
This phase I trial studies best dose and side effects of liposome-encapsulated
daunorubicin-cytarabine (CPX-351) and how well it works in treating patients with high risk
myelodysplastic syndrome or chronic myelomonocytic leukemia that has come back or has not
responded to treatment. Drugs used in chemotherapy, such as liposome-encapsulated
daunorubicin-cytarabine, work in different ways to stop the growth of cancer cells, either by
killing the cells, by stopping them from dividing, or by stopping them from spreading.
Detailed Description
PRIMARY OBJECTIVES:
I. To characterize the safety and tolerability of CPX-351 in patients with intermediate-2 or
high-risk myelodysplastic syndrome (MDS). (Dose Escalation Stage) II. To determine the
maximum tolerated dose (MTD) of intravenous CPX-351 in patients with intermediate-2 or
high-risk MDS. (Dose Escalation Stage) III. To further characterize the safety and
tolerability of CPX-351 in patients with intermediate-2 and high-risk MDS. (Dose-Expansion
Stage) IV. To evaluate preliminary efficacy of CPX-351 in patients with intermediate-2 or
high-risk MDS. (Dose-Expansion Stage)
SECONDARY OBJECTIVES:
I. To assess overall response (OR) rate. II. To assess overall survival. III. To assess
duration of response. IV. To assess relapse-free survival. V. To assess safety profile.
OUTLINE: This is a dose-escalation study.
INDUCTION THERAPY: Patients receive liposome-encapsulated daunorubicin-cytarabine
intravenously (IV) over 90 minutes on days 1, 3, and 5 in the absence of disease progression
or unacceptable toxicity. After 2-5 weeks, patients who do not achieve a complete response
(CR)/CR with incomplete bone marrow recovery (CRi)/CR with incomplete platelet recovery
(CRp), have acceptable or no toxicity, and have stable disease and no disease progression may
receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 in
the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Patients who achieve at least a hematological improvement (HI)
response, receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1
and 3. Treatment repeats every 28 days for up to 12 cycles in the absence of disease
progression or unacceptable toxicity. After 5-8 weeks, patients who do not show clinically
significant disease progression or unacceptable toxicity may receive liposome-encapsulated
daunorubicin-cytarabine for up to 12 additional cycles.
After completion of study treatment, patients are followed up at 30 days and then every 6
months thereafter.
Trial Arms
Name | Type | Description | Interventions |
---|
Treatment (liposome-encapsulated daunorubicin-cytarabine) | Experimental | INDUCTION THERAPY: Patients receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1, 3, and 5 in the absence of disease progression or unacceptable toxicity. After 2-5 weeks, patients who do not achieve a CR/CRi/CRp, have acceptable or no toxicity, and have stable disease and no disease progression may receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3 in the absence of disease progression or unacceptable toxicity.
CONSOLIDATION THERAPY: Patients who achieve at least a HI response, receive liposome-encapsulated daunorubicin-cytarabine IV over 90 minutes on days 1 and 3. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. After 5-8 weeks, patients who do not show clinically significant disease progression or unacceptable toxicity may receive liposome-encapsulated daunorubicin-cytarabine for up to 12 additional cycles. | - Liposome-encapsulated Daunorubicin-Cytarabine
|
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of MDS or chronic myelomonocytic leukemia (CMML) according to World Health
Organization (WHO)
- Patients are either not eligible for or choose not to proceed with a stem cell
transplant at the time of enrollment
- MDS and CMML classified by International Prognostic Scoring System (IPSS) as
intermediate-2/high risk with excess blasts > 5%, or with 10-19% bone marrow blasts
- No response following at least 4 cycles of therapy or relapse after initial CR,
partial response (PR), or HI or progression after any number of cycles of either
azacitidine, decitabine, guadecitabine or ASTX727 (oral decitabine) as single agents
or in combination with other investigational agents
- Patient (or patient's legally authorized representative) must have signed an informed
consent document indicating that the patient understands the purpose of and procedures
required for the study and is willing to participate in the study
- Total bilirubin < 3 mg/dL (will allow less than 5 x upper limit of normal [ULN] if
Gilbert's at investigator's discretion)
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 3 x ULN
- Serum creatinine clearance > 30 mL/min and no end/stage renal disease
- Hydroxyurea for control of leukocytosis or use of hematopoietic growth factors (eg,
granulocyte-colony stimulating factor [G-CSF], granulocyte-macrophage
colony-stimulating factor [GM-CSF], procrit, aranesp, thrombopoietins) is allowed at
any time prior to or during study if considered to be in the best interest of the
patient
Exclusion Criteria:
- New York Heart Association (NYHA) class III or IV congestive heart failure or left
ventricular ejection fraction (LVEF) < 50 by echocardiogram or multigated acquisition
(MUGA) scan
- History of myocardial infarction within the last 6 months or unstable/uncontrolled
angina pectoris or history of severe and/or uncontrolled ventricular arrhythmias
- Uncontrolled infection not adequately responding to appropriate antibiotics
- Female patients who are pregnant or lactating
- Patients with reproductive potential who are unwilling to following contraception
requirements (including condom use for males with sexual partners, and for females:
prescription oral contraceptives [birth control pills], contraceptive injections,
intrauterine devices [IUD], double-barrier method [spermicidal jelly or foam with
condoms or diaphragm], contraceptive patch, or surgical sterilization) throughout the
study
- Female patients with reproductive potential who have a positive urine or blood
beta-human chorionic gonadotropin (beta HCG) pregnancy test at screening
- Patients receiving any other concurrent investigational agent or chemotherapy,
radiotherapy, or immunotherapy (within 14 days of initiating study treatment)
- Prior cumulative anthracycline exposure of > 550 mg/m^2 daunorubicin or equivalent, or
> 400 mg/m^2 in patients who received radiation therapy to the mediastinum
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Incidence of adverse events (dose-escalation stage) |
Time Frame: | Up to 30 days |
Safety Issue: | |
Description: | Safety data of the patients will be summarized using descriptive statistics such as mean, standard deviation, median, and range. Toxicity type, severity, and attribution will be summarized for each patient using frequency tables. |
Secondary Outcome Measures
Measure: | Overall response rate |
Time Frame: | Up to 1.5 years |
Safety Issue: | |
Description: | |
Measure: | Overall survival |
Time Frame: | Up to 1.5 years |
Safety Issue: | |
Description: | The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests. |
Measure: | Duration of response |
Time Frame: | Up to 1.5 years |
Safety Issue: | |
Description: | Will be summarized using descriptive statistics such as mean, standard deviation, median and range. |
Measure: | Relapse-free survival |
Time Frame: | Up to 1.5 years |
Safety Issue: | |
Description: | The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier. Comparisons of time-to-event endpoints by important subgroups will be made using the log-rank tests. |
Measure: | Incidence of adverse events |
Time Frame: | Up to 1.5 years |
Safety Issue: | |
Description: | Safety data of the patients will be summarized using descriptive statistics such as mean, standard deviation, median, and range. Toxicity type, severity, and attribution will be summarized for each patient using frequency tables. |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | M.D. Anderson Cancer Center |
Last Updated
October 7, 2019