Luspatercept + Darbepoetin for Myelodysplastic Syndrome

(DarbeLus Trial)

Overseen By Stephanie Ladd

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Yale University

Must not be taking: ESAs, Hypomethylating agents

Disqualifiers: Seizures, Stroke, Thrombosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 22

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, luspatercept (a red blood cell production stimulator) and darbepoetin alfa (a synthetic form of erythropoietin), for individuals with myelodysplastic syndrome (MDS). Researchers aim to determine if these drugs can reduce the need for blood transfusions in people with MDS who rely on them regularly. Participants should have a lower-risk form of MDS, require frequent blood transfusions, and have a low level of natural erythropoietin (a hormone that aids in red blood cell production). As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to potentially benefit from innovative therapies.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take certain drugs like other red blood cell growth factors, some chemotherapy agents, and specific immunomodulating drugs during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both luspatercept and darbepoetin have been studied separately for treating anemia in patients with myelodysplastic syndromes (MDS). In these studies, patients generally tolerated the treatments well.

For luspatercept, studies found that nearly half of the patients experienced improved blood counts after 24 weeks, indicating effectiveness for many without severe side effects.

Darbepoetin has long been used to help with anemia, though some patients eventually stop responding to it. Despite this, it is generally considered safe.

Using these two treatments together is a new approach, but studies have shown they are safe when used alone. For those considering joining a trial for this combination, existing evidence suggests a good safety record, although individual experiences may vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatment options for myelodysplastic syndrome, which typically include medications like erythropoiesis-stimulating agents (ESAs), the combination of luspatercept and darbepoetin offers a novel approach. Luspatercept works by enhancing late-stage red blood cell maturation, which is a different mechanism from traditional ESAs that primarily boost early red blood cell production. This unique mechanism may improve anemia management more effectively. Researchers are excited because this combination has the potential to optimize red blood cell production and reduce the need for blood transfusions, offering a promising new avenue for patients who haven't responded well to standard treatments.

What evidence suggests that luspatercept and darbepoetin could be effective for myelodysplastic syndrome?

Research has shown that luspatercept can reduce the need for blood transfusions in patients with lower-risk myelodysplastic syndrome (MDS), with over 70% of patients requiring fewer transfusions. Darbepoetin, another treatment tested in this trial, increases red blood cell production. Studies found that switching from darbepoetin to luspatercept improved hemoglobin levels and quality of life. In this trial, participants will receive a combination of luspatercept and darbepoetin, which work together to improve blood health and reduce the need for transfusions in MDS patients. ^{1 2 3 6 7}

Who Is on the Research Team?

Maximilian Stahl, MD

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

This trial is for people with lower-risk Myelodysplastic Syndrome (MDS) who need regular red blood cell transfusions and have a natural erythropoietin (EPO) level below 500 IU/L. It's not specified who can't join, but typically there are criteria based on age, other health conditions, and previous treatments.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

I can care for myself but may not be able to do heavy physical work.

I am 18 years old or older.

Exclusion Criteria

I do not have an ongoing serious infection that isn't getting better with treatment.

I have severe, life-threatening complications from my blood cancer.

I do not have high blood pressure or a history of strokes or mini-strokes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive luspatercept and darbepoetin alfa every 21 days (three weeks) in combination therapy

48 weeks

Every 21 days (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

42 days

1 visit (in-person)

Long-term follow-up

Participants are assessed for long-term outcomes and red blood cell transfusion independence

Approximately 2.5 years

What Are the Treatments Tested in This Trial?

Interventions

• Darbepoetin
• Luspatercept

Trial Overview The study is testing the combination of two drugs: Luspatercept and Darbepoetin Alfa. Since it's an open-label Phase II trial, everyone gets the same treatment without any placebo or comparison group, and both participants and researchers know what's being given.

How Is the Trial Designed?

Group I: Luspatercept + Darbepoetin Experimental Treatment 2 Interventions

Each participant will be treated with luspatercept every 21 days (three weeks) in combination with darbepoetin alfa every 21 days (three weeks). Both agents will be administered on day 1 of each 21-day cycle. Based on the individual participant's response to combination therapy of luspatercept and darbepoetin alfa, the doses of luspatercept and/or darbepoetin alfa can be either decreased or increased. The starting dose is luspatercept at 1.0 mg/kg (Dose Level 0) and darbepoetin alfa 300 µg (Dose Level 0).

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07096297

NCT07096297 | Luspatercept + Darbepoetin in MDS This is a single arm open-label Phase II trial of luspatercept and darbepoetin alfa in SF3B1 wild type, lower-risk, RBC transfusion dependent MDS participants ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123130709

Improved Quality of Life upon Shifting from Darbepoetin to ... We are reporting successful shifting of two patients from Darbepoietin to Luspatercept with significant increase in Hb level and improvement in quality of life.

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1111/bjh.20126

How to use luspatercept and erythropoiesis‐stimulating ... In the EPOANE study, results were consistent, and erythroid response was obtained in 25% of TD LR-MDS patients versus 66.7% of NTD patients.

4. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/6714/528736/Efficacy-of-Luspatercept-on-Transfusion-Burden-and

Efficacy of Luspatercept on Transfusion Burden and ... Among patients with platelets less than 100K, 16% (n=5/31) achieved a platelet response (HI-P); while 59% (n=10/17) of patients with an ANC < ...

5. bloodcancerstoday.com bloodcancerstoday.com/post/making-headway-in-mds-two-novel-agents-for-advanced-lower-risk-mds-treatment

Two Novel Agents for Advanced Lower-Risk MDS Treatment Updated data presented in 2024 showed that more than 70.0% of patients assigned to luspatercept had achieved the primary endpoint of transfusion ...

6. ashpublications.org ashpublications.org/blood/article/133/8/790/260592/Luspatercept-for-the-treatment-of-anemia-in

Luspatercept for the treatment of anemia in myelodysplastic ... In addition to frequent primary resistance, most EPO or darbepoetin responders eventually relapse in 70% of the cases without progression to higher-risk MDSs ...

7. ajmc.com ajmc.com/view/luspatercept-promising-against-anemia-in-mds

Luspatercept Promising Against Anemia in MDS The study's results show that at 24 weeks, 47.6% of patients achieved a hematological improvement-erythroid response, significantly surpassing ...