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Myelodysplastic/Myeloproliferative Neoplasm With Ring Sideroblasts and Thrombocytosis, Not Otherwise SpecifiedPhase 2NCT05005182

Luspatercept With or Without Hydroxyurea for the Treatment of Myelodysplastic/Myeloproliferative Neoplasms With Ring Sideroblasts and Thrombocytosis or Unclassifiable With Ring Sideroblasts

A Phase 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Myelodysplastic/Myeloproliferative Neoplasm With Ring Sideroblasts and Thrombocytosis, Not Otherwise Specified and Myelodysplastic/Myeloproliferative Neoplasm, Not Otherwise Specified, run by Mayo Clinic at 3 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase II trial studies the effects of luspatercept with or without hydroxyurea in treating patients with myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis or unclassifiable with ring sideroblasts. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
3 sitesUnited States
Study dates
20 Feb 2023to 17 Jun 2023
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age >= 18 years
  • Patients with a World Health Organization(WHO)-defined diagnosis of MDS/MPN-RS-T or MDS/MPN-U with >= 15% RS
  • Prior treatment with lenalidomide, hypomethylating agents, immunosuppressive therapy, erythropoietin stimulating agents (ESA) or investigational agent is allowed as long as patients have not received luspatercept-aamt or sotatercept. If there is prior history of investigational agent, there should be an interval equivalent to at least four elimination half-lives of the agent prior to enrollment. Note: For patients who have received prior lenalidomide, hypomethylating agents, or immunosuppressive therapy, there must be >= 6 weeks since the last dose before luspatercept-aamt treatment is started
  • Eastern Cooperative Oncology Group (ECOG) performance score of 0, 1 or 2
  • Requirement of red blood cell transfusions (>= 2 unit =< 8-weeks prior to registration) OR symptomatic anemia with hemoglobin < 9.5 g/dL OR hematocrit < 30% (as long as there is documentation of adequate iron stores (ferritin > 50 mg/L) =< 5 weeks prior to registration). Symptomatic anemia is defined as fatigue with or without exertion, shortness of breath with or without exertion, or decrease in exercise tolerance
  • Hemoglobin =< 9.5 g/dL (obtained =< 14 days prior to registration)
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  • Total bilirubin =< 1.5 x upper limit of normal (ULN) (obtained =< 14 days prior to registration)
  • Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 3 x ULN (=< 5 x ULN for patients with liver involvement) (obtained =< 14 days prior to registration)
  • Calculated creatinine clearance >= 30 ml/min using the Cockcroft-Gault (obtained =< 14 days prior to registration)
  • 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:
  • Must have two negative urine or serum pregnancy tests as verified by the investigator prior to starting study therapy. A negative pregnancy test must be done =< 7 days prior to registration. Patient 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 during the study therapy (including dose interruptions), and for 84 days after discontinuation of study therapy
  • 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)
  • Male participants 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)
  • Provide written informed consent
  • Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)
  • Willingness to provide mandatory blood specimens for correlative research

Who cannot join

  • Any of the following because this study involves an agent that has known genotoxic, mutagenic and teratogenic effects:
  • Pregnant persons
  • Nursing persons
  • Persons of childbearing potential who are unwilling to employ highly effective contraception
  • Any of the following prior therapies:
  • Surgery =< 3 weeks prior to registration
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  • Chemotherapy or other agents =< 2 weeks prior to registration
  • Uncontrolled intercurrent non-cardiac illness including, but not limited to:
  • Ongoing or active infection
  • Uncontrolled hypertension (defined as systolic blood pressure >= 140 mmHg or diagnostic blood pressure >= 90 mmHg despite use of >= 3 anti-hypertensive drugs at optimal doses)
  • Psychiatric illness/social situations
  • Dyspnea at rest due to complications of advanced malignancy or other disease that requires continuous oxygen therapy
  • Clinically significant (symptomatic) anemia either due to nutritional deficiencies or iron, vitamin B12, folate or gastrointestinal (GI) bleeding
  • Any other conditions that would limit compliance with study requirements
  • Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy
  • NOTE: Patients known to be HIV positive, but without clinical evidence of an immunocompromised state (CD4 =< 200 x 10^6/L), are eligible for this trial
  • Receiving any other drug (except hydroxyurea) or investigational agent which would be considered as a treatment for the primary disease, that is, MDS/MPN-RS-T or MDS/MPN-U with RS =< 2 weeks prior to registration
  • Other active malignancy =< 3 years prior to registration. Patients on hormonal therapy for treated breast or prostate cancer are permitted if they meet other eligibility criteria
  • EXCEPTIONS: Non-melanotic skin cancer or carcinoma-in-situ of the cervix. NOTE: If there is a history of prior malignancy, they must not be receiving other specific treatment (luteinizing hormone-releasing hormone (LHRH) agonists for prostate cancer, and treatment with bisphosphonates and receptor activator of nuclear factor kappa-B ligand [RANKL] inhibitors) for their cancer
  • History of myocardial infarction, stroke, embolism, deep vein or arterial thrombosis =< 6 months prior to registration, or congestive heart failure requiring use of ongoing maintenance therapy for life-threatening ventricular arrhythmias

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • Mayo Clinic Hospital in Arizona

    Phoenix, Arizona, 85054

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: Phase II Study to Determine the Efficacy and Safety of Luspatercept (ACE-536) in Patients With Myelodysplastic/Myeloproliferative Neoplasms With Ring Sideroblasts and Thrombocytosis (MDS/MPN-RS-T) and Myelodysplastic/Myeloproliferative Neoplasms, Unclassifiable With Ring Sideroblasts (MDS/MPN-U With RS)

This phase II trial studies the effects of luspatercept with or without hydroxyurea in treating patients with myelodysplastic/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis or unclassifiable with ring sideroblasts. Biological therapies, such as luspatercept, use substances made from living organisms that may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Hydroxyurea may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving luspatercept with or without hydroxyurea may help doctors determine what doses of the combination is safe for patients to take and how the disease responds to the treatment.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To document the erythroid response rate assessed as per the 2015 International Working Group (IWG) myelodysplastic (MDS)/myeloproliferative neoplasms (MPN) response criteria.

SECONDARY OBJECTIVES:

  1. To document response duration, time to acute myeloid leukemia (AML) transformation, AML-free survival (LFS) and overall survival (OS) in patients with MDS/MPN-with ring sideroblasts (RS) and thrombocytosis (T) and MDS/MPN-unclassifiable (U)U with RS.

II. To document safety of luspatercept (luspatercept-aamt) in patients with MDS/MPN-RS-T and MDS/MPN-U with RS.

EXPLORATORY OBJECTIVE:

  1. To assess overall health-related quality of life as measured by Hematological Malignancy Specific Patient-Reported Outcome Measure (HM-PRO).

CORRELATIVE RESEARCH OBJECTIVE:

I: To find an effective biomarker of response to luspatercept-aamt.

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT A: Patients receive luspatercept subcutaneously (SC) on day 1. Cycles repeat every 21 days for 6 months in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, bone marrow biopsy and aspirate at baseline and on study.

COHORT B: Patients receive luspatercept SC on day 1 and hydroxyurea orally (PO) on days 1-21. Cycles repeat every 21 days for 6 months in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, bone marrow biopsy and aspirate at baseline and on study.

After completion of study treatment, patients are followed up every 3 months.

Being tested
Biospecimen Collection, Bone Marrow Aspiration, Bone Marrow Biopsy, Hydroxyurea, Luspatercept
Medical subject headings
Thrombocytosis, Myeloproliferative Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow biopsy and aspirate

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy and aspirate

  • HydroxyureaDrug

    Also called Droxia, Hydrea, Hydroxycarbamide, Litalir

    Given PO

  • LuspaterceptBiological

    Also called ACE-536, Luspatercept-aamt, Reblozyl

    Given SC

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT05005182
Study groupRoleWhat they receive
Cohort A (luspatercept)ExperimentalPatients receive luspatercept SC on day 1. Cycles repeat every 21 days for 6 months in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, bone marrow biopsy and aspirate at baseline and on study.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Biological: Luspatercept; Other: Questionnaire Administration
Cohort A (luspatercept, hydroxyurea)ExperimentalPatients receive luspatercept SC on day 1 and hydroxyurea PO on days 1-21. Cycles repeat every 21 days for 6 months in the absence of disease progression or unacceptable toxicity. Patients undergo blood sample collection, bone marrow biopsy and aspirate at baseline and on study.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Hydroxyurea; Biological: Luspatercept; Other: Questionnaire Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Erythroid Response Rate

    Defined as the proportion of patients who achieve an erythroid response out of the total number of evaluable patients (i.e. eligible patients who received at least one dose of treatment on study).

    Measured: 8 weeks

Secondary outcomes (5)

  1. Incidence of Adverse Events (AEs)

    AEs as well as toxicities (AEs felt to be at least possibly related to study treatment) will be reported in the adverse events section of the report. The count of participants by cohort that were evaluated for address events is reported here.

    Measured: 3 months, 29 days

  2. Duration of Response

    Time from erythroid response to progression or death.

    Measured: 69 days

  3. Time to Leukemic Transformation

    Will be evaluated and characterized within each cohort using the methods of Kaplan and Meier.

    Measured: 6 months

  4. Leukemia-free Survival

    Will be evaluated and characterized within each cohort using the methods of Kaplan and Meier.

    Measured: From time of treatment to progression to acute myeloid leukemia or death from any cause, assessed up to 6 months

  5. Overall Survival

    Will be evaluated and characterized within each cohort using the methods of Kaplan and Meier.

    Measured: 117 117 days [was intended to be 'Up to 6 months' (duration of treatment), but study terminated early due to slow accrual]

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Aug 2021
  2. Study start20 Feb 2023
  3. Primary completion17 Apr 2023
  4. Study completion17 Jun 2023

Why it stopped: Slow accrual

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05005182
Sponsor's protocol ID
MC200805
Other IDs
NCI-2021-08519, 20-013021
Status last verified
Sep 2024
First submitted
9 Aug 2021
Last updated
19 Sep 2024
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Patnaik MM, Tefferi A. Luspatercept use for lower risk myelodysplastic syndromes: Active but not enough. Am J Hematol. 2023 Aug;98(8):1171-1175. doi: 10.1002/ajh.27003. Epub 2023 Jun 22. No abstract available.

    PubMed 37345627

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Bone Marrow Biopsy in people with Myelodysplastic/Myeloproliferative Neoplasm With Ring Sideroblasts and Thrombocytosis, Not Otherwise Specified and Myelodysplastic/Myeloproliferative Neoplasm, Not Otherwise Specified, run by Mayo Clinic at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Sep 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Erythroid Response Rate (time frame: 8 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05005182, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Sep 2024.

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