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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Myelodysplastic Syndromes; Anemia; Myeloproliferative Neoplasm
• Intervention / Treatment: Drug: Luspatercept

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rami Komrokji, MD; Phone Number: 813-745-4748; Email: Rami.Komrokji@moffitt.org

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
      • Contact: Lisa Nardelli; Phone Number: 813-745-4731; Email: Lisa.Nardelli@moffitt.org
      • Principal Investigator: Rami Komrokji, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

   1. According to WHO 2016 classification
   2. Meets IPSS-R classification of very low, low, or intermediate risk disease

4. Documented acquired splicing gene mutation

   1. Cohort 1: detectable splicing mutation other than SF3B1: (SRSF2, U2AF1, ZRSR2)
   2. Cohort 2: SF3B1 mutation with prior treatment with hypomethylating agent and or lenalidomide
5. <5% blasts in bone marrow

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

   1. Refractory to prior ESA treatment - non-response or response that is no longer maintained.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
   2. Intolerant to prior ESA treatment - discontinuation of prior ESA-containing regimen, at any time after introduction due to intolerance or AE
   3. ESA ineligible - Low chance of response to ESA based on endogenous serum EPO > 200 U/L for subjects not previously treated with ESAs
7. Discontinuation of ESAs, G-CSF, GM-CSF ≥ 4 weeks prior to start of study treatment

8. Require RBC transfusions

   a. Average of ≥ 2 units/8 weeks of pRBCs confirmed for a minimum of 16 weeks immediately preceding registration

9. Applies to on treatment subjects only - females of childbearing potential (FCBP) defined as a sexually mature woman who:

   1. has achieved menarche at some point,
   2. has not undergone a hysterectomy or bilateral oophorectomy, or

   3. 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
10. investigational product (IP), during the study therapy (including dose interruptions), and for 84 days after discontinuation of study therapy

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

    1. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RBC Transfusion Independence	RBC transfusion independence (RBC-TI) as defined by IWG 2006 MDS response criteria	From start of treatment to up to 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of treatment related adverse events	To determine the number of participants with treatment related AEs using CTCAE v5	From start of treatment to 30 days after the last day of treatment, up to 19 months
Hematological Improvement	Hematological improvement as defined by using IWG 2006 MDS response criteria	From start of treatment to up to 18 months
Duration of Response	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.	From start of treatment to up to 18 months
ASC specks changes with response	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	End of treatment, up to 18 months

Collaborators and Investigators

• Sponsor: H. Lee Moffitt Cancer Center and Research Institute
• Collaborators: Bristol-Myers Squibb
• Investigators: Principal Investigator: Rami Komrokji, MD, Moffitt Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): February 21, 2023
• Primary Completion (Estimated): May 1, 2024
• Study Completion (Estimated): May 1, 2024

Study Registration Dates

• First Submitted: February 8, 2023
• First Submitted That Met QC Criteria: February 16, 2023
• First Posted (Actual): February 17, 2023

Study Record Updates

• Last Update Posted (Actual): January 25, 2024
• Last Update Submitted That Met QC Criteria: January 24, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: MPN; MDS; Non-Proliferative MDS; Non-Proliferative MPN
• Additional Relevant MeSH Terms: Pathologic Processes; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Neoplasms; Syndrome; Myelodysplastic Syndromes; Preleukemia; Anemia; Myeloproliferative Disorders; Hematinics; Luspatercept
• Other Study ID Numbers: MCC-21405

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No