A Randomized, Double-blind, Multicenter Study Comparing Magrolimab in Combination with Azacitidine versus Azacitidine Plus Placebo in Treatment-naïve Patients with Higher Risk Myelodysplastic Syndrome
- Conditions
- Myelodysplastic Syndrome ( a group of bone marrow disorders in which the production of blood cells is seriously disturbed)10018849
- Registration Number
- NL-OMON52320
- Lead Sponsor
- Gilead Sciences
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 14
1. Participants with MDS defined according to World Health Organization
classification, with an IPSS-R prognostic risk category of intermediate, high,
or very high risk. Note: participants who require AML-like therapy are not
eligible. Prior and concurrent therapy with hydroxyurea, oral etoposide,
erythroid, and/or myeloid growth factors is allowed.
2. White blood cell (WBC) count <= 20 × 10^3/µL prior to randomization. If the
participant*s WBC is > 20 × 10^3/µL prior to randomization, the participant
can be randomized, assuming all other eligibility criteria are met. Of note,
while this does not impact eligibility, please ensure that the WBC is <= 20 ×
10^3/µL prior to the first dose of study treatment and prior to each
magrolimab/placebo dose for priming doses of magrolimab.
a) Participants can be treated with hydroxyurea (up to 4 g/day) throughout the
study or prior to randomization to reduce the WBC to <= 20 × 10^3/µL to enable
eligibility and magrolimab dosing. Oral etoposide (up to 200 mg orally per day)
may be given as an alternative to hydroxyurea for participants who are
intolerant to hydroxyurea or cannot achieve sufficient WBC lowering on
hydroxyurea.
3. Participant has provided informed consent.
4. Participant is willing and able to comply with clinic visits and procedures
outlined in the study protocol.
5. Male or female, age >= 18 years.
6. Eastern Cooperative Oncology Group (ECOG) performance score of 0 to 2.
7. Willing to undergo blood transfusions as deemed clinically necessary.
8. Pretreatment blood cross-match including ABO (any of the 4 blood groups A,
B, AB, and O comprising the ABO system)/Rh (Rhesus factor), DAT (direct
antiglobulin test), and phenotyping or genotyping completed.
9. Biochemical indices within the ranges shown below:
a. Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase and
alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase <= 3× upper
limit of normal (ULN)
b. Total bilirubin <= 1.5 × ULN or 3.0 × ULN and primarily unconjugated if
participant has a documented history of Gilbert's syndrome or genetic equivalent
c. Serum creatinine <= 1.5 × ULN or calculated glomerular filtration rate (GFR)
>= 40 mL/min/1.73 m2
10. All participants must have a documented hemoglobin >=9.0 g/dL within 24
hours prior to the first two doses of magrolimab/placebo infusion. Participants
who do not meet these criteria must be transfused and have their hemoglobin
rechecked to meet the minimum haemoglobin threshold prior to administering each
of the first 2 doses of magrolimab/placebo. Transfusions are allowed in order
to meet hemoglobin eligibility.
11. Female participants of childbearing potential must not be nursing or
planning to be pregnant and must have a negative urine or serum pregnancy test
within 30 days before randomization and within 72 hours before the first
administration of study treatment.
12. Male participants and female participants of childbearing potential who
engage in heterosexual intercourse must agree to use protocol-specified methods
of contraception as described in protocol Appendix H.
13. Willing to consent to mandatory pretreatment and on-treatment bone marrow
biopsies (trephines), unless not feasible as determined by the Investigator and
discussed with the Sponsor.
1. Prior treatment with CD47 or SIRPa-targeting agents.
2. Prior therapy for the treatment of MDS with an IPSS-R prognostic risk
category of intermediate, high or very high risk (excluding hydroxyurea or oral
etoposide), prior treatment with hypomethylating agents and/or low dose
cytarabine. NOTE: Localized noncentral nervous system (CNS) radiotherapy,
erythroid and/or myeloid growth factors, previous hormonal therapy with
luteinizing hormone-releasing hormone (LHRH) agonists for prostate cancer, and
treatment with bisphosphonates and receptor activator of nuclear factor kappa-B
ligand (RANKL) inhibitors are not criteria for exclusion. Prior lenalidomide is
also not exclusionary.
3.Immediately eligible for an allogeneic SCT, as determined by the
Investigator, with an available donor.
4. Contraindications to azacitidine, including advanced malignant hepatic
tumors or known hypersensitivity to azacitidine or mannitol.
5. Known inherited or acquired bleeding disorders.
6. Previous SCT within 6 months prior to randomization, active
graft-versus-host disease, or requiring transplant-related immunosuppression.
7. Clinical suspicion of active CNS involvement by MDS.
8. Significant medical diseases or conditions, as assessed by the Investigators
and Sponsor, that would substantially increase the risk benefit ratio of
participating in the study. This includes, but is not limited to, acute
myocardial infarction within the last 6 months, unstable angina, uncontrolled
diabetes mellitus, significant active infections, and congestive heart failure
New York Heart Association Class III-IV.
9. Second malignancy, except treated basal cell or localized squamous skin
carcinomas, localized prostate cancer, or other malignancies for which
participants are not on active anticancer therapies and have had no evidence of
active malignancy for at least >= 1 year.
10. History of psychiatric illness or substance abuse likely to interfere with
the ability to comply with protocol requirements or give informed consent.
11. Pregnancy or active breastfeeding.
12. Known active or chronic hepatitis B or C infection or HIV infection in
medical history.
13. Active hepatitis B virus (HBV) and/or active hepatitis C virus (HCV),
and/or HIV following testing at screening:
a) Participants who test positive for hepatitis B surface antigen (HBsAg).
Participants who test positive for hepatitis B core antibody (anti-HBc) will
require HBV DNA by quantitative polymerase chain reaction (PCR) for
confirmation of active disease.
b) Participants who test positive for HCV antibody. These participants will
require HCV RNA by quantitative PCR for confirmation of active disease.
c) Participants who test positive for HIV antibody.
d) Participants not currently on antiviral therapy and who have an undetectable
viral load in the prior 3 months may be eligible for the study.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Endpoints:<br /><br><br /><br>* CR rate as assessed by Investigators:<br /><br>The CR rate is the proportion of participants who reach morphologic CR<br /><br>(morphological blast of <= 5% and recovery of ANC, platelets, and hemoglobin<br /><br>from CBS as well as peripheral blast collected on the same day) based on<br /><br>Investigator assessed IWG 2006 MDS criteria (Cheson 2006) prior to initiation<br /><br>of any new anticancer therapy for MDS, including SCT (stem cell transplant).<br /><br><br /><br>* Overall Survival (OS): The length of OS is measured from randomization to the<br /><br>date of death from any cause. Those who are not observed to die during the<br /><br>study will be censored at their last known alive date.</p><br>
- Secondary Outcome Measures
Name Time Method <p>See protocol section 3. Objectives and endpoints</p><br>