CPX-351 in Treating Patients With Newly Diagnosed, High-Risk Acute Myeloid Leukemia
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| ClinicalTrials.gov Identifier: NCT02286726 |
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Recruitment Status :
Active, not recruiting
First Posted : November 10, 2014
Last Update Posted : November 25, 2019
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Acute Myeloid Leukemia Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome Secondary Acute Myeloid Leukemia | Other: Laboratory Biomarker Analysis Drug: Liposome-encapsulated Daunorubicin-Cytarabine | Phase 2 |
PRIMARY OBJECTIVE:
I. To assess preliminary efficacy (as determined by the rate of complete response [CR] or CR with incomplete blood count recovery [CRi]) of two or three dose levels of CPX-351 in patients with newly diagnosed acute myeloid leukemia (AML) at high risk for induction mortality, defined as 30-50% predicted risk of death by day 60, and to select the most promising dose level for further efficacy testing.
SECONDARY OBJECTIVE:
I. To confirm the rate of dose limiting toxicities, including induction mortality (at day 60) for two different sub-maximum tolerated dose (MTD) dose levels (50 and 75 U/m^2).
EXPLORATORY OBJECTIVES:
I. To investigate the effect of CPX-351 on immune response, as determined by the effect on recovery of functional pathogen-specific and leukemia-specific immune responses and the recovery and function of natural killer (NK) cells.
II. To investigate the role of troponin-T as an early marker for CPX-351-induced cardiotoxicity.
III. To investigate ex vivo the cytotoxicity of combination of Pim-1 proto-oncogene, serine/threonine kinase (Pim) kinase inhibitor(s) and CPX-351 on circulating leukemia cells.
OUTLINE:
INDUCTION: Patients are randomized to 1 of 2 arms. After safety is established for both dose levels, and escalation is deemed feasible, an additional arm will be studied at the standard dose level.
ARM I: Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 intravenously (IV) over 90 minutes on days 1, 3, and 5 of a 28-day course. Patients with persistent disease may receive a second course with treatment on days 1 and 3.
ARM II: Patients receive intermediate-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients with persistent disease may receive a second course with treatment on days 1 and 3.
ARM III: Patients receive standard-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients with persistent disease may receive a second course with treatment on days 1 and 3.
CONSOLIDATION THERAPY: Patients achieving CR receive liposomal cytarabine-daunorubicin CPX-351 on days 1 and 3. Treatment may repeat every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up monthly for as long as the study doctor thinks it is needed, every 2-3 months for up to 1 year, and every 3-4 months for up to 1 year.
| Study Type : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 80 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Phase II Study of CPX-351 (Cytarabine:Daunorubicin) Liposome Injection in Patients With Newly Diagnosed AML at High Risk for Induction Mortality |
| Actual Study Start Date : | May 4, 2015 |
| Estimated Primary Completion Date : | May 31, 2021 |
| Estimated Study Completion Date : | May 31, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm I (lower-dose CPX-351)
Patients receive lower-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5 of a 28-day course. Patients with persistent disease may receive a second course with treatment on days 1 and 3.
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Other: Laboratory Biomarker Analysis
Correlative studies Drug: Liposome-encapsulated Daunorubicin-Cytarabine Given IV
Other Names:
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Experimental: Arm II (intermediate-dose CPX-351)
Patients receive intermediate-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients with persistent disease may receive a second course with treatment on days 1 and 3.
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Other: Laboratory Biomarker Analysis
Correlative studies Drug: Liposome-encapsulated Daunorubicin-Cytarabine Given IV
Other Names:
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Experimental: Arm III (standard-dose CPX-351)
Patients receive standard-dose liposomal cytarabine-daunorubicin CPX-351 IV over 90 minutes on days 1, 3, and 5. Patients with persistent disease may receive a second course with treatment on days 1 and 3.
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Other: Laboratory Biomarker Analysis
Correlative studies Drug: Liposome-encapsulated Daunorubicin-Cytarabine Given IV
Other Names:
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- Complete response (CR)/CR with incomplete blood count recovery (CRi) rate [ Time Frame: Up to 8 weeks (after induction therapy) ]Estimated for each arm with 95% confidence intervals. Fisher's exact test will be used to compare the response rate between the two dose levels.
- Incidence of dose-limiting toxicity [ Time Frame: Up to day 60 ]Defined as induction mortality (death occurring on or before day 60), grade 3 or 4 non-hematologic toxicity, or dose limiting hematologic toxicity at least possibly related to the study drug occurring during the first 28 days from the start of therapy. Estimated for each arm with 95% confidence intervals. Fisher's exact test will be used to compare the toxicity rate between the two dose levels.
- Immune response [ Time Frame: Up to 1 year ]Fisher's exact test will be used to compare immune responses between different doses of liposomal cytarabine-daunorubicin CPX-351.
- Troponin-T levels [ Time Frame: Up to 1 year ]Two-sample t test or analysis of variance or Fisher's exact test will be used to check the association between troponin-T and cardiotoxicity.
- Apoptosis of ex-vivo cultured leukemia cells [ Time Frame: Up to 1 year ]Two-sample t test or analysis of variance will be used to compare the apoptosis of ex-vivo cultured leukemia cells.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Ability to understand and voluntarily sign an informed consent form
- Pathological diagnosis of AML according to World Health Organization (WHO) criteria (with at least 20% blasts in the peripheral blood or bone marrow): newly diagnosed de novo AML; except for acute promyelocytic leukemia (APL); newly diagnosed secondary AML, defined as having a history of an antecedent hematologic disorder (myelodysplastic syndromes [MDS], myeloproliferative disease [MPD] or history of cytotoxic treatment for non-hematologic malignancy) or apparent de novo AML with MDS-associated karyotype
- Eastern Cooperative Oncology Group (ECOG) performance status 0-3
- Serum creatinine =< 2.0 mg/dL
- Serum total bilirubin =< 2.0 mg/dL
- Serum alanine aminotransferase < 3 times the upper limit of normal (ULN); Note: If elevated liver enzymes are related to disease alanine aminotransferase (ALT) should be < 5 times ULN
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To be considered at high risk for induction mortality patients must have 1 or 2 of the following risk factors (patients >= 60 must have at least 1 risk factor, patients < 60 must have at least 2 risk factors) present; at least one risk factor in every patient must be an AML-related factor:
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AML-related factors include:
- Antecedent hematologic disorder (AHD) (MDS, chronic myelomonocytic leukemia [CMML], or MPD) or history of exposure to cytotoxic chemotherapy [therapy-related (t)-AML]), or WHO-defined AML with MDS-related changes or apparent de novo AML with MDS-associated karyotype
- Unfavorable cytogenetics as defined by the European Leukemia Net
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Patient-related factors:
- Age >= 70
- ECOG performance status (PS) >= 2
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Co-morbidities:
- Serum creatinine > 1.3 g/dL
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- Cardiac ejection fraction >= 50% by echocardiography or multi gated acquisition (MUGA) (when left ventricular ejection fraction [LVEF] expressed as a range, at least the upper limit should include 50%)
- Able to adhere to the study visit schedule and other protocol requirements
- All men and women must agree to practice effective contraception during the study period if not otherwise documented to be infertile
Exclusion Criteria:
- Patients with history of second malignancy are eligible if they have documentation of disease stability, off therapy, based on computed tomography (CT) scan or other measures for the 6 months prior to entry in core
- Any serious medical condition or psychiatric illness that would prevent the patient from providing informed consent
- Chemotherapy or other investigational anticancer therapeutic drugs in the two weeks prior to study entry; in the event of rapidly proliferative disease, however, the use of hydroxyurea is permitted up to 24 hours before study entry in core
- Evidence of active central nervous system (CNS) leukemia
- Pregnant or lactating women
- Uncontrolled infection; to be eligible, patients receiving treatment for an infection (antibiotic, antifungal or antiviral treatment) must be afebrile (< 38.3 degrees Celsius [C]) and without hemodynamic instability or dyspnea from pneumonia for > 48 hours (hrs) prior to the start of induction therapy
- Hypersensitivity to cytarabine, daunorubicin or liposomal products
- History of Wilson's disease or other copper-metabolism disorder
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02286726
| United States, Texas | |
| M D Anderson Cancer Center | |
| Houston, Texas, United States, 77030 | |
| Principal Investigator: | Ghayas Issa | M.D. Anderson Cancer Center |
Additional Information:
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT02286726 History of Changes |
| Other Study ID Numbers: |
2014-0548 NCI-2014-02529 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ) 2014-0548 ( Other Identifier: M D Anderson Cancer Center ) P30CA016672 ( U.S. NIH Grant/Contract ) |
| First Posted: | November 10, 2014 Key Record Dates |
| Last Update Posted: | November 25, 2019 |
| Last Verified: | November 2019 |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Myelodysplastic Syndromes Neoplasms by Histologic Type Neoplasms Bone Marrow Diseases Hematologic Diseases Cytarabine Daunorubicin Antimetabolites, Antineoplastic Antimetabolites |
Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Antiviral Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors |