Sotatercept Combination Therapy for Multiple Myeloma

Recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Massachusetts General Hospital

Must be taking: Lenalidomide, Dexamethasone

Disqualifiers: Brain metastases, Allergic reactions, others

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

Compensation: Varies

Number of Visits: Unknown

33 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose of a new drug, ACE-011 (sotatercept), when combined with lenalidomide and dexamethasone for treating multiple myeloma. Researchers hope this combination will slow cancer growth and address issues like anemia and bone problems common in multiple myeloma patients. It suits those diagnosed with multiple myeloma who have undergone at least one prior treatment and possess specific cancer markers, such as certain proteins in the blood or urine. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have had chemotherapy or radiotherapy within 2 weeks before starting the study, and you must not have taken another investigational drug within 28 days prior to the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that ACE-011, also known as sotatercept, is generally safe and well-tolerated. In studies, patients with bone issues related to multiple myeloma (a type of blood cancer) have taken several doses of sotatercept without major problems. Reports indicate it is safe when combined with other treatments like lenalidomide and dexamethasone, which are commonly used for multiple myeloma. No major safety concerns have emerged so far, but as this is an early phase trial, researchers are still determining the optimal dose. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Sotatercept (ACE-011) is unique because it targets a new pathway in the treatment of multiple myeloma. Unlike standard treatments like proteasome inhibitors and immunomodulatory drugs, sotatercept works by modulating the transforming growth factor-beta (TGF-β) superfamily, which plays a role in bone health and cancer growth. This novel mechanism has the potential to not only treat the cancer but also improve bone density, which is often compromised in multiple myeloma patients. Researchers are excited because this dual action could offer a more comprehensive approach to managing the disease.

What evidence suggests that this treatment might be an effective treatment for multiple myeloma?

Studies have shown that sotatercept (ACE-011) can increase hemoglobin levels in people with blood disorders, potentially reducing the need for blood transfusions. In this trial, participants will receive sotatercept combined with lenalidomide or pomalidomide and dexamethasone. Research suggests that sotatercept, when used with these medications, might inhibit cancer cell growth and help manage anemia and bone problems in patients with multiple myeloma. Previous studies with sotatercept demonstrated positive effects on bone health and blood cell levels. These findings suggest that this treatment could help people with multiple myeloma by addressing both the cancer and its related symptoms. ^{1 2 3 4 6}

Who Is on the Research Team?

Andrew Yee, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for adults with multiple myeloma who've had at least one prior treatment. They must not be pregnant or breastfeeding, have a decent level of physical function (ECOG 0-2), and show specific signs of the disease in their blood, urine, or bone marrow. Those needing recent radiotherapy should wait two weeks post-treatment to join.

Inclusion Criteria

Monoclonal protein present in the serum and/or urine

Not pregnant or breastfeeding

My bone marrow has more than 10% plasma cells or I have a confirmed plasmacytoma.

Exclusion Criteria

I do not have brain metastases.

I have allergies to medications similar to ACE 011, Lenalidomide, or Dexamethasone.

I have not had major surgery in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose-escalation Treatment

Participants receive ACE-011, lenalidomide, and dexamethasone in 28-day cycles to determine the maximum tolerated dose

2 years

Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ACE-011

Trial Overview Researchers are testing Sotatercept (ACE-011) combined with Lenalidomide and Dexamethasone to find the highest safe dose against multiple myeloma. This study aims to see if this combo can slow cancer growth while helping anemia and bone issues related to the disease.

How Is the Trial Designed?

Group I: ACE-011 (sotatercept) Experimental Treatment 4 Interventions

ACE-011, Lenalidomide or pomalidomide, Dexamethasone

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Multiple Myeloma Research Consortium

Collaborator

Trials

21

Recruited

1,200+

Published Research Related to This Trial

Recent advancements in anti-myeloma treatments, including thalidomide, lenalidomide, and bortezomib, have shown significant clinical responses, especially in patients who do not respond to traditional chemotherapy.

The review highlights the ongoing development of various novel therapeutic classes, such as second-generation proteasome inhibitors and HDAC inhibitors, which are currently in clinical trials or advanced preclinical stages, indicating a promising expansion of treatment options for myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From the bench to the bedside: emerging new treatments in multiple myeloma. Mitsiades, CS., Hayden, PJ., Anderson, KC., et al.[2023]

The introduction of 18 new treatments for multiple myeloma over the past 12 years has significantly improved patient survival rates, extending median survival by 3 to 4 times.

Current treatment strategies emphasize the use of triplet therapies for both transplant and non-transplant patients, with maintenance therapies like lenalidomide showing benefits in prolonging progression-free and overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress and Paradigms in Multiple Myeloma. Anderson, KC.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4312883/

Sotatercept in patients with osteolytic lesions of multiple ... Overall, 25% of patients received all four sotatercept doses; 71% of sotatercept-treated patients had ≥1 dose interruption mainly due to increases in ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00747123

A Safety, Tolerability and Efficacy Study of ACE-011 in ... Multi-center, randomized, multiple-dose study to evaluate the safety, tolerability and efficacy of ACE-011 in patients with osteolytic lesions of multiple ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0753332223010302

The promise of sotatercept in hematologic disorders These results suggest that median or higher doses of sotatercept can effectively increase Hb levels in CIA patients and reduce the burden of transfusions and ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01562405

NCT01562405 | Sotatercept (ACE-011) With Lenalidomide ... It is possible that the combination of lenalidomide, dexamethasone and ACE 011 may reduce or prevent the growth of cancer cells along with improving anemia ...

5. jons-online.com jons-online.com/issues/2018/april-2018-vol-9-no-4/sotatercept-a-first-in-class-agent-improves-hemoglobin-levels-in-anemic-patients-with-myelofibrosis

Sotatercept, a First-in-Class Agent, Improves Hemoglobin ... Of the 24 patients receiving sotatercept monotherapy, 20 had primary myelofibrosis. Their median baseline hemoglobin level was 7.5 g/dL. A JAK2 driver mutation ...

6. accp1.onlinelibrary.wiley.com accp1.onlinelibrary.wiley.com/doi/full/10.1002/jcph.160

Multiple‐dose, safety, pharmacokinetic, and ... Results of the present study indicate that sotatercept, an ActRIIA ligand trap, achieves clinically relevant increases in hemoglobin, hematocrit ...