Filgrastim, Cladribine, Cytarabine, and Mitoxantrone With Sorafenib in Treating Patients With Newly-Diagnosed, Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome
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|ClinicalTrials.gov Identifier: NCT02728050|
Recruitment Status : Recruiting
First Posted : April 5, 2016
Last Update Posted : January 8, 2021
|Condition or disease||Intervention/treatment||Phase|
|Acute Biphenotypic Leukemia Acute Myeloid Leukemia de Novo Myelodysplastic Syndrome Myelodysplastic Syndrome Myeloproliferative Neoplasm||Drug: Cladribine Drug: Cytarabine Biological: Filgrastim Other: Laboratory Biomarker Analysis Other: Quality-of-Life Assessment Drug: Mitoxantrone Drug: Sorafenib||Phase 1 Phase 2|
OUTLINE: This is a phase I, dose-escalation study of mitoxantrone and sorafenib followed by a phase II study.
INDUCTION: Patients receive mitoxantrone intravenously (IV) over 60 minutes on days 1-3 and sorafenib orally (PO) twice daily (BID) on days 10-19 in the absence of disease progression or unacceptable toxicity. Patients also receive filgrastim subcutaneously (SC) once daily (QD) on days 0-5, cladribine IV QD over 2 hours on days 1-5, and cytarabine IV QD over 2 hours on days 1-5 in the absence of disease progression or unacceptable toxicity. Patients achieving partial remission (including MRD positive [pos] CR, CR with incomplete platelet recovery [CRp], and CR with incomplete count recovery [CRi]) or persistent AML may receive up to 2 cycles of induction therapy per the discretion of the treating physician.
POST-REMISSION: Patients receive sorafenib PO BID on days 8-27 or 3 days prior to next cycle of treatment, whichever occurs first. Patients also receive filgrastim subcutaneously SC QD on days 0-5, cladribine IV QD over 2 hours on days 1-5, and cytarabine IV QD over 2 hours on days 1-5 in the absence of disease progression or unacceptable toxicity. Patients achieving MRDneg CR may receive up to 4 cycles of post-remission therapy. Patients achieving disease response (MRDpos CR, CRi/CRp, or persistent disease) may receive up to two induction cycles and 1 cycle of post-remission therapy with mitoxantrone omitted in cycle 3. If they then enter MRDneg CR, they can proceed with up to a total of 4 cycles of post-remission therapy.
MAINTENANCE THERAPY: Patients achieving MRDneg CR may receive maintenance therapy of sorafenib PO BID for up to 1 year.
After completion of study treatment, patients are followed up every 3 months for up to 5 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||82 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Addition of Sorafenib to G-CSF, Cladribine, Cytarabine, and Mitoxantrone (G-CLAM) in Adults With Newly-Diagnosed Acute Myeloid Leukemia (AML) Independent of FLT3-ITD Status: A Phase 1/2 Study|
|Actual Study Start Date :||December 1, 2016|
|Estimated Primary Completion Date :||October 31, 2022|
|Estimated Study Completion Date :||October 31, 2025|
Experimental: Treatment (sorafenib, G-CLAM)
See Detailed Description.
Other: Laboratory Biomarker Analysis
Other: Quality-of-Life Assessment
Other Name: Quality of Life Assessment
- Maximum tolerated dose (MTD) (Phase I) [ Time Frame: 28 days ]Will be defined as the highest dose studied in which the incidence of dose-limiting toxicity is < 33% assuming at least 6 patients have been treated at this dose.
- Minimal residual disease negative (MRDneg) complete response (CR) rate (Phase II) [ Time Frame: 56 days (2 cycles of induction chemotherapy) ]
- Complete response (CR) [ Time Frame: Up to 5 years ]
- Overall response rate (ORR) [ Time Frame: Up to 5 years ]
- Overall survival (OS) [ Time Frame: Up to 5 years ]
- Event-free survival (EFS) [ Time Frame: Up to 5 years ]
- Relapse-free survival (RFS) [ Time Frame: Up to 5 years ]
- Incidence of toxicity [ Time Frame: Up to 5 years ]Will be assessed using National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
- Quality of life (QOL) scores [ Time Frame: Up to 5 years ]Will be assessed by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30. Will be recorded and summarized using descriptive methods including boxplots, histograms, and statistical summary measures (medians, means, standard deviation, N, and proportions).
- Costs, obtained by cost records [ Time Frame: Up to 5 years ]Will be recorded and summarized using descriptive methods including boxplots, histograms, and statistical summary measures (medians, means, standard deviation, N, and proportions).
- Number of days in hospital [ Time Frame: Up to 5 years ]
- Number of hospital admissions [ Time Frame: Up to 5 years ]
- Mean duration of hospital stays [ Time Frame: Up to 5 years ]
- Number of days in the intensive care unit [ Time Frame: Up to 5 years ]
- Number of blood product transfusions received [ Time Frame: Up to 5 years ]
- Number of episodes of febrile neutropenia [ Time Frame: Up to 5 years ]
- Number of days requiring antibiotic use [ Time Frame: Up to 5 years ]
- Number of visits to the emergency department [ Time Frame: Up to 5 years ]
- Number of clinic visits [ Time Frame: Up to 5 years ]
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): NCT02728050
|Contact: Anna Halpernfirstname.lastname@example.org|
|United States, Washington|
|Fred Hutch/University of Washington Cancer Consortium||Recruiting|
|Seattle, Washington, United States, 98109|
|Contact: Anna Halpern 206-606-1978 email@example.com|
|Principal Investigator: Anna Halpern|
|Principal Investigator:||Anna Halpern||Fred Hutch/University of Washington Cancer Consortium|