Clinical Trials /

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

NCT04798339

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 Erythropoietin Stimulating Agent (ESA)

Related Conditions:
  • Myelodysplastic Syndromes
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Canakinumab With Darbepoetin Alfa in PTs With Lower-Risk MDS Who Have Failed ESA
  • Official Title: 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)

Clinical Trial IDs

  • ORG STUDY ID: MCC-20552
  • SECONDARY ID: CACZ885TUS02T
  • NCT ID: NCT04798339

Conditions

  • Myelodysplastic Syndromes

Interventions

DrugSynonymsArms
Canakinumab InjectionIlarisPhase 1b: Dose Level 1
Darbepoetin AlfaAranespPhase 1b: Dose Level 1

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1b: Dose Level 1ExperimentalPatients 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.
  • Canakinumab Injection
  • Darbepoetin Alfa
Phase 1b: Dose Level 2ExperimentalPatients 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.
  • Canakinumab Injection
  • Darbepoetin Alfa
Phase 2: Treatment at Maximum Tolerated DoseExperimentalPatients 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.
  • Canakinumab Injection
  • Darbepoetin Alfa

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.)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Phase 1b: Maximum Tolerated Dose (MTD)
Time Frame:up to 28 days per cohort
Safety Issue:
Description: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).

Secondary Outcome Measures

Measure:Phase 1b and Phase 2: Duration of Hematologic Improvement-Erythroid (HI-E) response
Time Frame:Up to 12 months per cohort
Safety Issue:
Description: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.
Measure:Phase 1b and Phase 2: Degree in reduction of PRBC Transfusions
Time Frame:at 24 weeks per cohort
Safety Issue:
Description: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
Measure:Phase 2: Overall Response Rate (ORR)
Time Frame:Up to 60 months
Safety Issue:
Description: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
Measure:Phase 2: Duration of Response
Time Frame:Up to 60 months
Safety Issue:
Description: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.
Measure:Phase 2: Overall Survival (OS)
Time Frame:Up to 60 months
Safety Issue:
Description:OS is defined as the duration of time starting from first treatment with canakinumab until death
Measure:Phase 2: Progression Free Survival (PFS)
Time Frame:Up to 60 months
Safety Issue:
Description: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.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:H. Lee Moffitt Cancer Center and Research Institute

Trial Keywords

  • MDS

Last Updated

March 15, 2021