Sotatercept (ACE-011) With Lenalidomide or Pomalidomide and Dexamethasone in Relapsed/Refractory Multiple Myeloma

Sponsor
Massachusetts General Hospital (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT01562405
Collaborator
Multiple Myeloma Research Consortium (Other)
33
4
1
121
8.3
0.1

Study Details

Study Description

Brief Summary

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 and bone lesions that sometimes occur in people with multiple myeloma.

This current study is the first study combining ACE 011 with lenalidomide. In this research study, the investigators are looking for the highest dose of ACE 011 that can be given with lenalidomide and dexamethasone. The investigators will also begin to collect information about the effect of the combination of ACE 011, lenalidomide and dexamethasone on multiple myeloma.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

After the screening procedures confirm that you are eligible to participate in the research study:

Assignment to dose level of study treatment Since we are looking for the highest dose of the ACE 011 combined with lenalidomide that can be administered safely without severe or unmanageable side effects in participants that have multiple myeloma, not everyone who participates in this research study will receive the same dose of these drugs. The dose you get will depend on the number of participants who have been enrolled in the study before you and how well they have tolerated their doses.

Study treatment Study treatment will be given in 28 day cycles.

  • ACE-011 will be given as an injection under the skin, Day 1 of each cycle (every 28 days). You will receive each injection at the clinic.

  • Lenalidomide will be taken by mouth: once daily days 1 21, followed by a 7 day rest period during which no lenalidomide will be taken.

  • Dexamethasone will be taken by mouth once per week (days 1, 8, 15 and 22) of each cycle.

You will be given drug diaries to record the doses of lenalidomide and dexamethasone taken. The study staff will tell you how to complete the diaries

Study Design

Study Type:
Interventional
Actual Enrollment :
33 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 1, Multicenter, Open-label, Dose-escalation Study of Sotatercept (ACE-011) in Combination With Lenalidomide or Pomalidomide and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma
Study Start Date :
May 1, 2012
Anticipated Primary Completion Date :
Jun 1, 2022
Anticipated Study Completion Date :
Jun 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: ACE-011 (sotatercept)

ACE-011, Lenalidomide or pomalidomide, Dexamethasone

Drug: ACE-011
Injection every 28 days, dose escalation levels from 15-45 mg
Other Names:
  • Sotatercept
  • Drug: Lenalidomide
    15 to 25 mg days 1-21, given orally
    Other Names:
  • Revlimid
  • Drug: Dexamethasone
    40 mg days 1,8,15,22; given orally
    Other Names:
  • Decadron
  • Drug: Pomalidomide
    Pomalidomide 4 mg daily on days 1-21
    Other Names:
  • Pomalyst
  • Outcome Measures

    Primary Outcome Measures

    1. Maximum Tolerated Dose of ACE-011 [2 years]

      Identify the maximum tolerated dose of ACE-011 given in combination with lenalidomide and dexamethasone in subjects with relapsed multiple myeloma

    Secondary Outcome Measures

    1. Efficacy of ACE-011 [2 years]

      Objective response according to the International Myeloma Working Group Uniform Response Criteria Duration of response Time to progression Progression-free survival

    2. Safety of ACE-011 [2 years]

      Adverse events profile Toxicity profile as per NCI CTCAE v4.0

    3. Pharmacodynamic measures [2 years]

      -Activin levels

    4. Pharmacodynamic markers [2 years]

      Markers of bone turnover

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Monoclonal plasma cells in the bone marrow > 10% and/or presence of a biopsy-proven plasmacytoma

    • Monoclonal protein present in the serum and/or urine

    • Patient must have received at least 1 line of prior systemic therapy for the treatment of multiple myeloma. A line of treatment is sequential treatment without interruption for response and subsequent progression

    • 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.

    • ECOG performance status of zero to two unless decline is due to bony disease

    • Not pregnant or breastfeeding

    Exclusion Criteria:
    • Participants who have had chemotherapy or radiotherapy within 2 weeks (6 weeks for nitrosureas 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 because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events.

    • History of allergic reactions attributed to compounds of similar chemical or biologic composition to ACE 011, Lenalidomide or Dexamethasone

    • 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

    • Individuals with a history of a different malignancy 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 cancers are eligible if diagnosed and treated within the past 5 years: 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Emory University Atlanta Georgia United States 30322
    2 Massachusetts General Hosptial Boston Massachusetts United States 02115
    3 Brigham and Women's Hospital Boston Massachusetts United States 02215
    4 Dana-Farber Cancer Institute Boston Massachusetts United States 02215

    Sponsors and Collaborators

    • Massachusetts General Hospital
    • Multiple Myeloma Research Consortium

    Investigators

    • Principal Investigator: Andrew J. Yee, MD, Massachusetts General Hospital

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Andrew Yee, MD, Principal Investigator, Massachusetts General Hospital
    ClinicalTrials.gov Identifier:
    NCT01562405
    Other Study ID Numbers:
    • 11-318
    First Posted:
    Mar 23, 2012
    Last Update Posted:
    Oct 29, 2021
    Last Verified:
    Oct 1, 2021
    Keywords provided by Andrew Yee, MD, Principal Investigator, Massachusetts General Hospital
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 29, 2021