This study is a multi-institution, open-label, Phase 1b/2 clinical trial evaluating the toxicity and efficacy of canakinumab in combination with darbepoetin alfa in patients with lower-risk MDS who have failed prior treatment with an Erythropoietin Stimulating Agent (ESA)
This study is a multi-institution, open-label, Phase 1b/2 clinical trial evaluating the toxicity and efficacy of canakinumab in combination with darbepoetin alfa in patients with lower-risk MDS who have failed prior treatment with an ESA. The study will be conducted in two parts, an initial Phase 1b dose escalation study followed by a dose expansion phase.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
13
Participants will be treated at 1 of 2 dose levels of Canakinumab, beginning at 150 mg and increasing to 300 mg or the Maximum Tolerated Dose
Participants will receive Darbepoetin alfa subcutaneously at a dose of 300mg on days 1 and 15 of each cycle
Moffitt Cancer Center
Tampa, Florida, United States
Emory-Winship Cancer Institute
Atlanta, Georgia, United States
Phase 1b: Maximum Tolerated Dose (MTD)
Maximum tolerated Dose will be determined by testing increasing doses of canakinumab along with a fixed dose of darbepoetin alfa. Patients will be followed for at least 1 cycle before the safety of each cohort can be fully assessed and decisions made for dose escalation in the next cohort. The MTD is defined as the dose level below which DLT is manifested in ≥33% of the patients or at dose level 2 if DLT is manifested in \<33% of the patients (with at 6 patients treated at the MTD).
Time frame: up to 28 days per cohort
Phase 2: Rate of Hematologic Improvement-Erythroid (HI-E) response
To determine the rate of hematologic improvement-erythroid (HI-E) response, defined as red blood cell transfusion independence (RBC-TI) of at least 8 weeks in transfusion dependent patients or a mean Hgb increase of \>/=1.5g/dL above baseline sustained for at least 8 weeks in non-transfusion dependent patients.
Time frame: 8 - 12 weeks from baseline
Phase 1b and Phase 2: Duration of Hematologic Improvement-Erythroid (HI-E) response
Duration of HI-E response: defined as the total duration for which patient is free from transfusions, or in non-transfusion dependent patients, the duration of sustained Hgb improvement of ./=1.5g/dL above pre-treatment baseline.
Time frame: Up to 12 months per cohort
Phase 1b and Phase 2: Degree in reduction of PRBC Transfusions
Degree in reduction of PRBC Transfusions: defined as the total reduction in absolute number of units of PRBCs transfused over the first 24 weeks on study versus the number of units of PRBCs during the 16 weeks prior to treatment
Time frame: at 24 weeks per cohort
Phase 2: Overall Response Rate (ORR)
Overall Response Rate (ORR) is defined by achieving a complete response (CR), partial response (PR), marrow CR (mCR) or hematologic improvement (HI) by IWG 2006 response criteria in MDS
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Time frame: Up to 60 months
Phase 2: Duration of Response
Duration of response is defined as the duration that begins on the day patient first achieves a response, until the day that patient loses response/progresses as per IWG criteria or dies.
Time frame: Up to 60 months
Phase 2: Overall Survival (OS)
OS is defined as the duration of time starting from first treatment with canakinumab until death
Time frame: Up to 60 months
Phase 2: Progression Free Survival (PFS)
PFS is defined as the duration of time starting from first treatment with canakinumab until death or disease progression or transformation, as defined by IWG 2006 criteria.
Time frame: Up to 60 months