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Epoetin Alfa

Darbepoetin alfa

Patients will be treated at dose level 1: Canakinumab 150 mg by subcutaneous injection on day 1 of each 28 day cycle. Darbepoetin alfa will be administered subcutaneously at a dose of 300mg on days 1 and 15 of each cycle.

Patients will be treated at dose level 2: Canakinumab 300 mg by subcutaneous injection on day 1 of each 28 day cycle. Darbepoetin alfa will be administered subcutaneously at a dose of 300mg on days 1 and 15 of each cycle.

Patients will be treated with Darbepoetin alfa subcutaneously at a dose of 300 mg on days 1 and 15 of each cycle plus the maximum tolerated dose of Canakinumab.

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

Canakinumab Injection

Participants will receive Darbepoetin alfa subcutaneously at a dose of 300mg on days 1 and 15 of each cycle

Darbepoetin Alfa

Lisa Nardelli

David A Sallman, MD

Rami Komrokji, MD

Timothy E Kubal, MD, MBA

Andrew T Kuykendall, MD

Jeffrey E Lancet, MD

Eric Padron, MD

Kendra L Sweet, MD

Chetasi Talati, MD

Aaliyah Guillory

Anthony Hunter, MD

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.

Canakinumab With Darbepoetin Alfa in PTs With Lower-Risk MDS Who Have Failed ESA

A Phase 1b/2 Study Evaluating the Safety and Efficacy of Canakinumab With Darbepoetin Alfa in Patients With Lower-Risk Myelodysplastic Syndromes (MDS) Who Have Failed Erythropoietin Stimulating Agents (ESA)

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).

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.

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.

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

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

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.

OS is defined as the duration of time starting from first treatment with canakinumab until death

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.

Novartis Pharmaceuticals

H. Lee Moffitt Cancer Center and Research Institute

Inflammation

Anemia

200 mg canakinumab subcutaneously every three weeks

Administration for a duration of 6 months for all patients and in case of response further treatment for up to three years

Anne Sophie Kubasch, Dr.

Hematologic improvement of erythrocytes after 6 months of canakinumab treatment.

To study the erythroid response rate (HI-E) of canakinumab in patients with IPSS-R very low, low, or intermediate risk MDS or MDS/MPN after 6 months of treatment.

Efficacy and Safety of Canakinumab for the Treatment of Anemia in LR-MDS Patients

A Phase II, Single-Arm, Open-Label Study to Assess the Efficacy and Safety of Canakinumab for the Treatment of Anemia in Patients With IPSS-R Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes or MDS/MPN

Erythroid response rate (HI-E) of canakinumab

Duration of erythroid response rate will be measured up to loss of response or reaching end of study (after max. 3 years of treatment)

The safety profile of canakinumab will be described by collecting AE (adverse event) and SAE (serious adverse event) information up to the start of new treatment or reaching end of study (after max. 3 years of treatment). Special consideration will be laid on events that lead to treatment discontinuation.

Proportion of disease progression (after reaching PD at any time during the trial after primary end-point visit)

QoL assessment using the QUALMS questionnaire up to end of treatment:

38-item assessment tool for patients with Myelodysplastic Syndromes (MDS) QUALMS scores ranged from 24 to 99, with higher scores for better outcome

QoL assessment using the EORTC-C30 questionnaire up to end of treatment:

To assess patient-reported quality of life during canakinumab treatment: 30 questions assessing the quality of life of oncology patients across 10 subscales will be analyzed. All subscales have a score range from 0 to 100 points.

Function subscales: a higher score represents a higher quality of life. Symptoms subscales: higher score represents higher level of symptoms/problems, i.e., represents lower quality of life

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Canakinumab With Darbepoetin Alfa in PTs With Lower-Risk MDS Who Have Failed ESA	NCT04798339	Myelodysplastic...	Canakinumab Inj... Darbepoetin Alf...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Canakinumab With Darbepoetin Alfa in PTs With Lower-Risk MDS Who Have Failed ESA	NCT04798339	Myelodysplastic...	Canakinumab Inj... Darbepoetin Alf...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
Efficacy and Safety of Canakinumab for the Treatment of Anemia in LR-MDS Patients	NCT05237713	Anemia Myelodysplastic...	Canakinumab Inj...	18 Years -	University of Leipzig
Canakinumab With Darbepoetin Alfa in PTs With Lower-Risk MDS Who Have Failed ESA	NCT04798339	Myelodysplastic...	Canakinumab Inj... Darbepoetin Alf...	18 Years -	H. Lee Moffitt Cancer Center and Research Institute

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