Luspatercept for Anemia in Lower Risk MDS or Non-proliferative MDS/MPN Neoplasms

Sponsor
H. Lee Moffitt Cancer Center and Research Institute (Other)
Overall Status
Recruiting
CT.gov ID
NCT05732961
Collaborator
Bristol-Myers Squibb (Industry)
70
1
2
14.7
4.8

Study Details

Study Description

Brief Summary

The purpose of the study is to see if participants with anemia due to their type of MDS or MDS/MPN will experience a more decreased need for regular blood transfusions if they take luspatercept plus best supportive care, and what effect, good and/or bad, luspatercept has on them and their anemia due to MDS or MDS/MPN. The safety and tolerability of luspatercept will also be evaluated in this study.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
70 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2, Single Arm Study of Luspatercept for the Treatment of Anemia in Lower Risk Myelodysplastic Syndromes (MDS) or Non-Proliferative Myelodysplastic Syndromes/ Myeloproliferative Neoplasms (MDS/MPN)
Actual Study Start Date :
Feb 8, 2023
Anticipated Primary Completion Date :
May 1, 2024
Anticipated Study Completion Date :
May 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Participants with gene mutations other than SF3B1

Participants with lower risk MDS or non-proliferative MDS/MPN with somatic splicing gene mutations other than SF3B1

Drug: Luspatercept
Participants will be treated with Luspatercept, with a starting dose of 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle)
Other Names:
  • ACE-536
  • Experimental: Participants with SF3B1 mutation

    Participants with lower risk MDS or non-proliferative MDS/MPN with SF3B1 mutation who had received hypomethylating agents and or lenalidomide.

    Drug: Luspatercept
    Participants will be treated with Luspatercept, with a starting dose of 1.0 mg/kg subcutaneous injection every 3 weeks (administered on Day 1 of each 21-day treatment cycle)
    Other Names:
  • ACE-536
  • Outcome Measures

    Primary Outcome Measures

    1. RBC Transfusion Independence [From start of treatment to up to 18 months]

      RBC transfusion independence (RBC-TI) as defined by IWG 2006 MDS response criteria

    Secondary Outcome Measures

    1. Incidence of treatment related adverse events [From start of treatment to 30 days after the last day of treatment, up to 19 months]

      To determine the number of participants with treatment related AEs using CTCAE v5

    2. Hematological Improvement [From start of treatment to up to 18 months]

      Hematological improvement as defined by using IWG 2006 MDS response criteria

    3. Duration of Response [From start of treatment to up to 18 months]

      The duration of response is measured from the time measurement criteria are met for RBC TI or HI by IWG 2006 criteria until the first date of loss of response or progressive disease is objectively documented.

    4. ASC specks changes with response [End of treatment, up to 18 months]

      ASC specks as biomarker of response, investigators will compare mean baseline percentage of ASC specks among responders and non-responders (t-test) and use paired t-test to compare change in mean percentage of ASC specks with treatment among responders and non-responders

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    1. Participant is ≥18 years at the time of signing the informed consent form

    2. Participant is willing and able to adhere to the study visit schedule and other protocol requirements

    3. Documented diagnosis of MDS or non-proliferative MDS/MPN (WBC < 13,000 U/L)

    4. According to WHO 2016 classification

    5. Meets IPSS-R classification of very low, low, or intermediate risk disease

    6. Documented acquired splicing gene mutation

    7. Cohort 1: detectable splicing mutation other than SF3B1

    8. Cohort 2: SF3B1 mutation with prior treatment with hypomethylating agent and or lenalidomide

    9. <5% blasts in bone marrow

    10. Refractory, intolerant to, or ineligible for, prior ESA treatment, as defined by any one of the following:

    11. Refractory to prior ESA treatment - non-response or response that is no longer maintained. ESA regimen must have been either:

    • rHu EPO ≥ 40,000 IU/wk for at least 8 doses or equivalent Or darbepoetin alpha ≥ 500 μg Q3W for at least 4 doses or equivalent
    1. Intolerant to prior ESA treatment - discontinuation of prior ESA-containing regimen, at any time after introduction due to intolerance or AE

    2. ESA ineligible - Low chance of response to ESA based on endogenous serum EPO > 200 U/L for subjects not previously treated with ESAs

    3. Discontinuation of ESAs, G-CSF, GM-CSF ≥ 4 weeks prior to start of study treatment

    4. Require RBC transfusions

    1. Average of ≥ 2 units/8 weeks of pRBCs confirmed for a minimum of 16 weeks immediately preceding registration
    1. Applies to on treatment subjects only - females of childbearing potential (FCBP) defined as a sexually mature woman who:

    2. has achieved menarche at some point,

    3. has not undergone a hysterectomy or bilateral oophorectomy, or

    4. has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months) and must:

    • Have two negative pregnancy tests 48 hours apart as verified by the investigator prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. This applies even if the subject practices true abstinence* from heterosexual contact.

    • Either commit to true abstinence*from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with highly effective, contraception without interruption, 35 days prior to starting

    1. investigational product (IP), during the study therapy (including dose interruptions), and for 84 days after discontinuation of study therapy

    2. Applies to on treatment subjects only - Male subjects must:

    3. Practice true abstinence* (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for at least 84 days following investigational product discontinuation even if he has undergone a successful vasectomy. * True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception).

    Exclusion Criteria:
    1. Prior allogeneic or autologous stem cell transplant

    2. MDS associated with del 5q cytogenetic abnormality if no prior lenalidomide treatment

    3. Uncontrolled hypertension, defined as repeated elevations of diastolic blood pressure (DBP) ≥ 100 mmHg despite adequate treatment

    4. ANC < 500/μL (0.5 x 109/L)

    5. Platelet count ˂50,000/μL (50 x 109/L)

    6. Active other malignancies

    7. Severe renal impairment (eGFR < 30 mL/min/1.73 m2)

    8. ALT or AST ≥ 3 × ULN

    9. Prior treatment with Luspatercept or Sotatercept

    10. Pregnant or breastfeeding females

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Moffitt Cancer Center Tampa Florida United States 33612

    Sponsors and Collaborators

    • H. Lee Moffitt Cancer Center and Research Institute
    • Bristol-Myers Squibb

    Investigators

    • Principal Investigator: Rami Komrokji, MD, Moffitt Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    H. Lee Moffitt Cancer Center and Research Institute
    ClinicalTrials.gov Identifier:
    NCT05732961
    Other Study ID Numbers:
    • MCC-21405
    First Posted:
    Feb 17, 2023
    Last Update Posted:
    Feb 17, 2023
    Last Verified:
    Feb 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by H. Lee Moffitt Cancer Center and Research Institute
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Feb 17, 2023