Sotatercept, Lenalidomide or Pomalidomide, and Dexamethasone in Treating Patients with Relapsed or Refractory Multiple Myeloma

Status: Active


This phase I trial studies the side effects and best dose of sotatercept when given together with lenalidomide or pomalidomide, and dexamethasone in treating patients with multiple myeloma that has returned (relapsed) or has not responded to treatment (refractory). Biological therapies, such as sotatercept, lenalidomide, pomalidomide, and dexamethasone, may stimulate the immune system in different ways and stop cancer cells from growing. Giving sotatercept together with lenalidomide or pomalidomide, and dexamethasone may also improve anemia (low blood levels of hemoglobin) and bone lesions that may occur in patients with multiple myeloma.

Eligibility Criteria

Inclusion Criteria

  • Relapsed or relapsed/refractory multiple myeloma (MM) with progressive disease (PD) parameters according to International Myeloma Working Group (IMWG) criteria * Refractory is defined as experiencing less than minimal response to or PD within 60 days of the most recent line therapy * Relapsed is defined as patients requiring salvage therapy for PD who are not refractory to the most recent line of therapy
  • Relapsed patients must have measurable disease; patients without measurable disease may be considered after discussion with principal investigator
  • Participant must have received at least one prior line of treatment of multiple myeloma; for pomalidomide-containing arm(s), patients must have received at least one prior line of treatment and must have undergone prior treatment with at least 2 cycles of lenalidomide and at least 2 cycles of proteasome inhibitor (either in separate regimens or within the same regimen) unless not a candidate
  • For participants treated with local radiotherapy with or without concomitant exposure to steroids, for pain control or management of cord/nerve root compression, two weeks must have lapsed since last date of radiotherapy, which is recommended to be a limited field; participants who require concurrent radiotherapy should have entry to the protocol deferred until the radiotherapy is completed and two weeks have passed since the last date of therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status of zero to two unless decline is due to bony disease
  • Serum bilirubin less than two times the institutional upper limits of normal (ULN); higher levels are acceptable if these can be attributed to active hemolysis, ineffective erythropoiesis, or Gilbert’s disease
  • Serum transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) less than three times the upper limits of normal (ULN)
  • Absolute neutrophil count (ANC) >= 1000/uL
  • Platelet count >= 50,000/ul; for patients with >= 50% plasma cell involvement of the bone marrow, platelet count >= 30,000/ul is acceptable
  • Creatinine clearance >= 30 mL/min
  • Women of childbearing potential (WCBP) must have a negative serum or urine pregnancy test within 7 days of starting study drug; in addition, sexually active WCBP must agree to use adequate contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; or barrier contraceptive with spermicide) while on study drug; WCBP must agree to have pregnancy tests every 4 weeks while on study drug
  • Hemoglobin 8-13 g/dL (patients with hemoglobin > 13 g/dL are excluded)
  • All study participants must be registered into the mandatory POMALYST REMS program and be willing and able to comply with the requirements of the POMALYST REMS program
  • Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the POMALYST REMS program
  • Ability to understand and the willingness to sign a written informed consent document
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately

Exclusion Criteria

  • Prior pomalidomide treatment (for patients on the pomalidomide arm)
  • Participants who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
  • Participants may not have received treatment with another investigational drug or device within 28 days prior to day 1, or if the half-life of the previous product is known, within 5 times the half-life prior to dosing, whichever may be longer
  • Participants with known brain metastases should be excluded from this clinical trial
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to sotatercept, lenalidomide, pomalidomide, or dexamethasone; participants with a prior history of allergic reaction to lenalidomide (grade 1-2) may be allowed to participate in the pomalidomide arm, after discussion with the principal investigator and if the use of pomalidomide would reflect standard practice
  • Bisphosphonates will not be allowed on the study while the participant is receiving sotatercept; prior bisphosphonate use is allowed
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with lenalidomide or pomalidomide
  • Individuals with a history of a malignancy (other than multiple myeloma) are ineligible except for the following circumstances; individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy
  • Individuals with the following non-invasive cancers are eligible: cervical cancer in situ, and basal cell or squamous cell carcinoma of the skin
  • History of major surgery within 30 days prior to trial initiation
  • Human immunodeficiency virus (HIV) infection
  • Active hepatitis B infection
  • Active hepatitis C infection

Locations & Contacts


Emory University Hospital / Winship Cancer Institute
Status: Active
Contact: Ajay Kumar Nooka
Phone: 404-779-1900


Brigham and Women's Hospital
Status: Active
Contact: Jacob Peter Laubach
Phone: 617-632-4218
Dana-Farber Cancer Institute
Status: Active
Contact: Jacob Peter Laubach
Phone: 617-632-4218
Massachusetts General Hospital Cancer Center
Status: Active
Contact: Andrew Jenho Yee
Phone: 617-724-4000

Trial Objectives and Outline


I. To identify the maximum tolerated dose of sotatercept given in combination with an immunomodulatory drug (IMiD) in subjects with relapsed and/or refractory multiple myeloma.


I. To evaluate the safety of sotatercept when given in combination with an IMiD and dexamethasone.

II. To evaluate the pharmacokinetics of sotatercept when given in combination with an IMiD and dexamethasone.

III. To explore pharmacodynamic markers of sotatercept when given in combination with an IMiD and dexamethasone.

IV. To evaluate the efficacy of sotatercept in combination with an IMiD and dexamethasone.

OUTLINE: This is a dose-escalation study of sotatercept.

Patients receive sotatercept subcutaneously (SC) on day 1, lenalidomide or pomalidomide orally (PO) once daily (QD) on days 1-21, and dexamethasone PO on days 1, 8, 15 and 22. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months for up to 3 years.

Trial Phase & Type

Trial Phase

Phase I

Trial Type


Lead Organization

Lead Organization
Dana-Farber Harvard Cancer Center

Principal Investigator
Andrew Jenho Yee

Trial IDs

Primary ID 11-318
Secondary IDs NCI-2012-00818 ID NCT01562405