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

NCT ID: NCT04798339

Last Updated: 2025-10-31

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-30
• Study Completion Date: 2026-07-31

Brief Summary

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)

Detailed Description

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.

Conditions

Myelodysplastic Syndromes

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1b: Dose Level 1

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.

Group Type: EXPERIMENTAL

Canakinumab Injection

Intervention Type: DRUG

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

Darbepoetin Alfa

Intervention Type: DRUG

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

Phase 1b: Dose Level 2

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.

Group Type: EXPERIMENTAL

Canakinumab Injection

Intervention Type: DRUG

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

Darbepoetin Alfa

Intervention Type: DRUG

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

Phase 2: Treatment at Maximum Tolerated Dose

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.

Group Type: EXPERIMENTAL

Canakinumab Injection

Intervention Type: DRUG

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

Darbepoetin Alfa

Intervention Type: DRUG

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

Interventions

Canakinumab Injection

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

Intervention Type: DRUG

Darbepoetin Alfa

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

Intervention Type: DRUG

Other Intervention Names

Ilaris; Aranesp

Eligibility Criteria

Inclusion Criteria

• Adequate organ function as defined by laboratory values per protocol
• Documented diagnosis of MDS by World Health Organization (WHO) criteria, further meeting the following criteria according to disease risk classification
• Patients must be transfusion dependent, defined as requirement for transfusion of at least 3 units of Packed Red Blood cells (PRBCs) 16 weeks for a Hgb<9.0g/dL or, in non-transfusion dependent patients (<3 units of PRBCs transfused in the preceding 16 weeks), must have a baseline Hgb of <9.0 g/dL at time of study enrollment
• Eastern Cooperative Oncology Group (ECOG) Performance Status </=2.
• Women of child bearing potential must have negative urine or serum pregnancy test within 28 days prior to start of study drug.
• Women of child bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence; tubal ligation, partner's vasectomy) prior to Cycle 1 Day 1 and for the duration of study participation.

Exclusion Criteria

• Use of chemotherapeutic agents or experimental agents (agents that are not commercially available) for the treatment of MDS within 14 days of the first day of study drug treatment.
• Previous treatment with a hypomethylating agent (such as azacitidine, decitabine or investigational hypomethylating agent).
• Use of concurrent growth factors such as G-CSF, GM-CSF, or thrombopoietin mimetics during study except in cases of febrile neutropenia, where G-CSF can be used for short term. Growth factors must be stopped two weeks prior to study.
• Patient has any of the following cardiac abnormalities: (a) Uncontrolled, symptomatic congestive heart failure as designated by the treating physician (b) Myocardial infarction ≤ 6 months prior to enrollment (c) Unstable angina pectoris as designated by the treating physician (d) Serious uncontrolled cardiac arrhythmia as designated by the treating physician. (e) Uncontrolled hypertension as designated by the treating physician
• Known history of human immunodeficiency virus (HIV) (no laboratory testing is required), or active infection with Hepatitis B or Hepatitis C.
• Active tuberculosis (Tb) infection or documented, untreated latent Tb infection (all patients should undergo Tb risk evaluation prior to enrollment with Tb screening performed as per local guidelines,
• Active, uncontrolled infection at the time of enrollment, except in cases of localized infections that are unlikely to lead to a systemic infection such as onychomycoses or dental caries. Patients with new fever (> 38.0 C) or respiratory symptoms are required to undergo laboratory screening for COVID-19
• Have undergone prior allo-HSCT for the treatment of MDS, or other hematologic disorder, or prior solid organ transplant.
• Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
• Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.
• Patients with a condition requiring systemic treatment with corticosteroids within 14 days of study drug administration (i.e. prednisone at doses of >10mg). Inhaled or topical steroids and adrenal/pituitary replacement doses >10mg daily prednisone equivalents are permitted.
• Patients undergoing concurrent treatment with agents targeting tumor necrosis factor alpha (TNF) or IL-1 within 28 days of study enrollment.
• Patients who have received a live-virus vaccine within 30 days before study drug administration (patients should not be treated with live-virus vaccine while undergoing therapy).
• History of allergy or hypersensitivity to either darbepoetin alfa or the study drug or its components.
• Women of child bearing potential who are pregnant or breastfeeding.
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness.)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David A Sallman, MD

Role: PRINCIPAL_INVESTIGATOR

Moffitt Cancer Center

Locations

Moffitt Cancer Center

Tampa, Florida, United States

Emory-Winship Cancer Institute

Atlanta, Georgia, United States

Countries

United States

Other Identifiers

CACZ885TUS02T

Identifier Type: OTHER

Identifier Source: secondary_id

MCC-20552

Identifier Type: -

Identifier Source: org_study_id