- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04798339
Canakinumab With Darbepoetin Alfa in PTs With Lower-Risk MDS Who Have Failed ESA
April 5, 2024 updated by: H. Lee Moffitt Cancer Center and Research Institute
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)
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)
Study Overview
Status
Recruiting
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Estimated)
41
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Florida
-
Tampa, Florida, United States, 33612
- Recruiting
- Moffitt Cancer Center
-
Contact:
- Lisa Nardelli
- Phone Number: 813-745-4731
- Email: Lisa.Nardelli@moffitt.org
-
Sub-Investigator:
- Rami Komrokji, MD
-
Sub-Investigator:
- Timothy E Kubal, MD, MBA
-
Sub-Investigator:
- Jeffrey E Lancet, MD
-
Sub-Investigator:
- Eric Padron, MD
-
Sub-Investigator:
- Kendra L Sweet, MD
-
Sub-Investigator:
- Chetasi Talati, MD
-
Principal Investigator:
- David A Sallman, MD
-
Sub-Investigator:
- Andrew T Kuykendall, MD
-
-
Georgia
-
Atlanta, Georgia, United States, 30322
- Recruiting
- Emory-Winship Cancer Institute
-
Principal Investigator:
- Anthony Hunter, MD
-
Contact:
- Aaliyah Guillory
- Phone Number: 404-778-5165
- Email: Aguill2@emory.edu
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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.)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 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.
|
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
Other Names:
Participants will receive Darbepoetin alfa subcutaneously at a dose of 300mg on days 1 and 15 of each cycle
Other Names:
|
Experimental: 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.
|
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
Other Names:
Participants will receive Darbepoetin alfa subcutaneously at a dose of 300mg on days 1 and 15 of each cycle
Other Names:
|
Experimental: 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.
|
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
Other Names:
Participants will receive Darbepoetin alfa subcutaneously at a dose of 300mg on days 1 and 15 of each cycle
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase 1b: Maximum Tolerated Dose (MTD)
Time Frame: up to 28 days per cohort
|
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).
|
up to 28 days per cohort
|
Phase 2: Rate of Hematologic Improvement-Erythroid (HI-E) response
Time Frame: 8 - 12 weeks from baseline
|
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.
|
8 - 12 weeks from baseline
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase 1b and Phase 2: Duration of Hematologic Improvement-Erythroid (HI-E) response
Time Frame: Up to 12 months per cohort
|
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.
|
Up to 12 months per cohort
|
Phase 1b and Phase 2: Degree in reduction of PRBC Transfusions
Time Frame: at 24 weeks per cohort
|
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
|
at 24 weeks per cohort
|
Phase 2: Overall Response Rate (ORR)
Time Frame: Up to 60 months
|
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
|
Up to 60 months
|
Phase 2: Duration of Response
Time Frame: Up to 60 months
|
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.
|
Up to 60 months
|
Phase 2: Overall Survival (OS)
Time Frame: Up to 60 months
|
OS is defined as the duration of time starting from first treatment with canakinumab until death
|
Up to 60 months
|
Phase 2: Progression Free Survival (PFS)
Time Frame: Up to 60 months
|
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.
|
Up to 60 months
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Principal Investigator: David A Sallman, MD, Moffitt Cancer Center
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
March 30, 2021
Primary Completion (Estimated)
June 28, 2024
Study Completion (Estimated)
June 28, 2024
Study Registration Dates
First Submitted
March 11, 2021
First Submitted That Met QC Criteria
March 11, 2021
First Posted (Actual)
March 15, 2021
Study Record Updates
Last Update Posted (Actual)
April 8, 2024
Last Update Submitted That Met QC Criteria
April 5, 2024
Last Verified
April 1, 2024
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- MCC-20552
- CACZ885TUS02T (Other Identifier: Novartis Pharmaceuticals)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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