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

Primary Purpose

Myelodysplastic Syndromes, Myeloproliferative Neoplasm, Anemia

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Luspatercept
Sponsored by
H. Lee Moffitt Cancer Center and Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelodysplastic Syndromes focused on measuring MDS, MPN, Non-Proliferative MDS, Non-Proliferative MPN

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Participant is ≥18 years at the time of signing the informed consent form Participant is willing and able to adhere to the study visit schedule and other protocol requirements Documented diagnosis of MDS or non-proliferative MDS/MPN (WBC < 13,000 U/L) According to WHO 2016 classification Meets IPSS-R classification of very low, low, or intermediate risk disease Documented acquired splicing gene mutation Cohort 1: detectable splicing mutation other than SF3B1 Cohort 2: SF3B1 mutation with prior treatment with hypomethylating agent and or lenalidomide <5% blasts in bone marrow Refractory, intolerant to, or ineligible for, prior ESA treatment, as defined by any one of the following: Refractory to prior ESA treatment - non-response or response that is no longer maintained.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 Intolerant to prior ESA treatment - discontinuation of prior ESA-containing regimen, at any time after introduction due to intolerance or AE ESA ineligible - Low chance of response to ESA based on endogenous serum EPO > 200 U/L for subjects not previously treated with ESAs Discontinuation of ESAs, G-CSF, GM-CSF ≥ 4 weeks prior to start of study treatment Require RBC transfusions a. Average of ≥ 2 units/8 weeks of pRBCs confirmed for a minimum of 16 weeks immediately preceding registration Applies to on treatment subjects only - females of childbearing potential (FCBP) defined as a sexually mature woman who: has achieved menarche at some point, has not undergone a hysterectomy or bilateral oophorectomy, or 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 investigational product (IP), during the study therapy (including dose interruptions), and for 84 days after discontinuation of study therapy Applies to on treatment subjects only - Male subjects must: 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: Prior allogeneic or autologous stem cell transplant MDS associated with del 5q cytogenetic abnormality if no prior lenalidomide treatment Uncontrolled hypertension, defined as repeated elevations of diastolic blood pressure (DBP) ≥ 100 mmHg despite adequate treatment ANC < 500/μL (0.5 x 109/L) Platelet count ˂50,000/μL (50 x 109/L) Active other malignancies Severe renal impairment (eGFR < 30 mL/min/1.73 m2) ALT or AST ≥ 3 × ULN Prior treatment with Luspatercept or Sotatercept Pregnant or breastfeeding females

Sites / Locations

  • Moffitt Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Participants with gene mutations other than SF3B1

Participants with SF3B1 mutation

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Incidence of treatment related adverse events
To determine the number of participants with treatment related AEs using CTCAE v5
Hematological Improvement
Hematological improvement as defined by using IWG 2006 MDS response criteria
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.
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

Full Information

First Posted
February 8, 2023
Last Updated
July 20, 2023
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT05732961
Brief Title
Luspatercept for Anemia in Lower Risk MDS or Non-proliferative MDS/MPN Neoplasms
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)
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 21, 2023 (Actual)
Primary Completion Date
May 2024 (Anticipated)
Study Completion Date
May 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndromes, Myeloproliferative Neoplasm, Anemia
Keywords
MDS, MPN, Non-Proliferative MDS, Non-Proliferative MPN

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
70 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Participants with gene mutations other than SF3B1
Arm Type
Experimental
Arm Description
Participants with lower risk MDS or non-proliferative MDS/MPN with somatic splicing gene mutations other than SF3B1
Arm Title
Participants with SF3B1 mutation
Arm Type
Experimental
Arm Description
Participants with lower risk MDS or non-proliferative MDS/MPN with SF3B1 mutation who had received hypomethylating agents and or lenalidomide.
Intervention Type
Drug
Intervention Name(s)
Luspatercept
Other Intervention Name(s)
ACE-536
Intervention Description
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)
Primary Outcome Measure Information:
Title
RBC Transfusion Independence
Description
RBC transfusion independence (RBC-TI) as defined by IWG 2006 MDS response criteria
Time Frame
From start of treatment to up to 18 months
Secondary Outcome Measure Information:
Title
Incidence of treatment related adverse events
Description
To determine the number of participants with treatment related AEs using CTCAE v5
Time Frame
From start of treatment to 30 days after the last day of treatment, up to 19 months
Title
Hematological Improvement
Description
Hematological improvement as defined by using IWG 2006 MDS response criteria
Time Frame
From start of treatment to up to 18 months
Title
Duration of Response
Description
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.
Time Frame
From start of treatment to up to 18 months
Title
ASC specks changes with response
Description
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
Time Frame
End of treatment, up to 18 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Participant is ≥18 years at the time of signing the informed consent form Participant is willing and able to adhere to the study visit schedule and other protocol requirements Documented diagnosis of MDS or non-proliferative MDS/MPN (WBC < 13,000 U/L) According to WHO 2016 classification Meets IPSS-R classification of very low, low, or intermediate risk disease Documented acquired splicing gene mutation Cohort 1: detectable splicing mutation other than SF3B1 Cohort 2: SF3B1 mutation with prior treatment with hypomethylating agent and or lenalidomide <5% blasts in bone marrow Refractory, intolerant to, or ineligible for, prior ESA treatment, as defined by any one of the following: 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 Intolerant to prior ESA treatment - discontinuation of prior ESA-containing regimen, at any time after introduction due to intolerance or AE ESA ineligible - Low chance of response to ESA based on endogenous serum EPO > 200 U/L for subjects not previously treated with ESAs Discontinuation of ESAs, G-CSF, GM-CSF ≥ 4 weeks prior to start of study treatment Require RBC transfusions a. Average of ≥ 2 units/8 weeks of pRBCs confirmed for a minimum of 16 weeks immediately preceding registration Applies to on treatment subjects only - females of childbearing potential (FCBP) defined as a sexually mature woman who: has achieved menarche at some point, has not undergone a hysterectomy or bilateral oophorectomy, or 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 investigational product (IP), during the study therapy (including dose interruptions), and for 84 days after discontinuation of study therapy Applies to on treatment subjects only - Male subjects must: 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: Prior allogeneic or autologous stem cell transplant MDS associated with del 5q cytogenetic abnormality if no prior lenalidomide treatment Uncontrolled hypertension, defined as repeated elevations of diastolic blood pressure (DBP) ≥ 100 mmHg despite adequate treatment ANC < 500/μL (0.5 x 109/L) Platelet count ˂50,000/μL (50 x 109/L) Active other malignancies Severe renal impairment (eGFR < 30 mL/min/1.73 m2) ALT or AST ≥ 3 × ULN Prior treatment with Luspatercept or Sotatercept Pregnant or breastfeeding females
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Rami Komrokji, MD
Phone
813-745-4748
Email
Rami.Komrokji@moffitt.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rami Komrokji, MD
Organizational Affiliation
Moffitt Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Lisa Nardelli
Phone
813-745-4731
Email
Lisa.Nardelli@moffitt.org
First Name & Middle Initial & Last Name & Degree
Rami Komrokji, MD

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

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

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