Blasts 10-19 Percent of Bone Marrow Nucleated CellsPhase 1NCT03896269

CPX-351 in Treating Patients With Relapsed or Refractory High Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia

A Phase 1 study testing Liposome-encapsulated Daunorubicin-Cytarabine in people with Blasts 10-19 Percent of Bone Marrow Nucleated Cells and Blasts More Than 5 Percent of Bone Marrow Nucleated Cells, run by M.D. Anderson Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Blasts 10-19 Percent of Bone Marrow Nucleated Cells, Blasts More Than 5 Percent of Bone Marrow Nucleated Cells, High Risk Chronic Myelomonocytic Leukemia
What is being tested?: Liposome-encapsulated Daunorubicin-Cytarabine
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 38 participants
Where: 1 siteUnited States
Study dates: 14 May 2019to 31 Dec 2027
Phase: Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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)

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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

Who cannot join

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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Guillermo M Bravo contact

713-794-3604

gmontalban1@mdanderson.org

United States1 site, 1 recruiting

M D Anderson Cancer Center
Houston, Texas, 77030
Guillermo M. Bravo, 713-794-3604
Guillermo M. Bravo
Recruiting

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

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:

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.

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
Being tested: Liposome-encapsulated Daunorubicin-Cytarabine
Medical subject headings: Leukemia, Myelomonocytic, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Liposome-encapsulated Daunorubicin-CytarabineDrug
Also called CPX-351, Cytarabine-Daunorubicin Liposome for Injection, Liposomal AraC-Daunorubicin CPX-351, Liposomal Cytarabine-Daunorubicin
Given IV

Study groups in NCT03896269
Study group	Role	What they receive
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. Receives: Drug: Liposome-encapsulated Daunorubicin-Cytarabine

What is being measured

The primary outcome is the main question the study is designed to answer.

Incidence of adverse events (dose-escalation stage)
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.
Measured: Up to 30 days
Maximum-tolerated dose (MTD) of liposome-encapsulated daunorubicin-cytarabine (dose-escalation stage)
Defined as the highest dose level in which a dose-limiting toxicity (DLT) occurs within at most 1 out of 6 patients treated. DLTs are defined as any related non-hematological Common Terminology Criteria for Adverse Events grade >= 3 adverse events that prevent further administration of the agent at that same dose level.
Measured: Up to 28 days
Incidence of adverse events (dose-expansion stage)
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.
Measured: Up to 30 days
Objective response rate (ORR) (dose-expansion stage)
Defined as complete response (CR), partial response, CR with incomplete bone marrow recovery, marrow CR or hematological improvement. Will be estimated along with 95% confidence intervals treated at the MTD (i.e., including those treated at the MTD during dose escalation and dose expansion phases). The association between ORR and patient's clinical characteristics will be examined by Wilcoxon's rank sum test or Fisher's exact test, as appropriate.
Measured: Up to 1.5 years

Secondary outcomes (5)

Overall response rate
Measured: Up to 1.5 years
Overall survival
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.
Measured: Up to 1.5 years
Duration of response
Will be summarized using descriptive statistics such as mean, standard deviation, median and range.
Measured: Up to 1.5 years
Relapse-free survival
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.
Measured: Up to 1.5 years
Incidence of adverse events
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.
Measured: Up to 1.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

14 May 201931 Dec 2027

First posted29 Mar 2019
Study start14 May 2019
Primary completion31 Dec 2027 (estimated)
Study completion31 Dec 2027 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Blasts 10-19 Percent of Bone Marrow Nucleated CellsStudies of the same condition, open and under way.
More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 38 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03896269
Sponsor's protocol ID: 2018-0911
Other IDs: NCI-2019-01558, 2018-0911
Status last verified: Oct 2026
First submitted: 28 Mar 2019
Last updated: 6 Oct 2026
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Montalban-Bravo G, Jabbour E, Borthakur G, Kadia T, Ravandi F, Chien K, Pemmaraju N, Hammond D, Dong XQ, Huang X, Schneider H, John R, Kanagal-Shamana R, Loghavi S, Kantarjian H, Garcia-Manero G. Phase 1/2 study of CPX-351 for patients with Int-2 or high risk International Prognostic Scoring System myelodysplastic syndromes and chronic myelomonocytic leukaemia after failure to hypomethylating agents. Br J Haematol. 2024 Mar;204(3):898-909. doi: 10.1111/bjh.19193. Epub 2023 Nov 10.
PubMed 37946611