Canakinumab and Darbepoetin Alfa for the Treatment of Lower-Risk Myelodysplastic Syndromes in Patients Who Have Failed Erythropoietin Stimulating Agents

Active:	Yes
Cancer Type:	Cancer-Related Syndrome Leukemia Myelodysplastic Syndromes (MDS)	NCT ID:	NCT04798339
Trial Phases:	Phase I Phase II	Protocol IDs:	MCC-20552 (primary) NCI-2021-02281
Eligibility:	18 Years and older, Male and Female	Study Type:	Treatment
Study Sponsor:	Moffitt Cancer Center
NCI Full Details:	http://clinicaltrials.gov/show/NCT04798339

Summary

This phase Ib/II trial finds the best dose of canakinumab and determines the safety and effect when it's given together with darbepoetin alfa in treating patients with lower-risk myelodysplastic syndromes who have failed erythropoietin stimulating agents. Canakinumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Darbepoetin alfa may help to stimulate the bone marrow to produce red blood cells. Giving canakinumab and darbepoetin alfa may kill more cancer cells.

Objectives

PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of canakinumab in combination with darbepoetin alfa as determined by DLTs occurring during the first treatment cycle. (Phase Ib)
II. To determine the rate of hematologic improvement-erythroid (HI-E) as per revised International Working Group (IWG) 2018 response criteria, defined as red blood cell transfusion independence (RBC-TI) of at least 8 weeks in transfusion dependent patients or a mean hemoglobin (Hgb) increase of >= 1.5 g/dL above baseline sustained for at least 8 weeks in non-transfusion dependent patients, during treatment with canakinumab. (Phase II)

SECONDARY OBJECTIVES:
I. To determine the duration of HI-E response.
II. To determine the degree of reduction in red blood cell transfusions.
III. To determine the complete response (CR) and overall response rate (ORR) by IWG 2006 response criteria in myelodysplastic syndrome (MDS).
IV. To determine the duration of response by IWG 2006 criteria.
V. To determine the overall survival (OS).
VI. To determine the progression free survival (PFS).
VII. To determine the effect on patient’s symptoms and quality of life (QoL).
VIII. To determine whether recurrent genetic mutations are predictive of response.
IX. To characterize in vivo IL-1beta inhibition with canakinumab.
X. To evaluate the relationship between changes in innate immune and pyroptosis biomarker indices with response to treatment.
XI. To determine the prevalence of infections, including opportunistic infections, associated with canakinumab therapy in MDS patients.

OUTLINE: This is a phase Ib, dose-escalation study of canakinumab followed by a phase II study.

Patients receive canakinumab subcutaneously (SC) on day 1 and darbepoetin alfa SC on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 6 months for 5 years.

Treatment Sites in Georgia

Winship Cancer Institute of Emory University
1365 Clifton Road NE
Building C
Atlanta, GA 30322
winshipcancer.emory.edu

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