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

NCT05005182 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: MC200805NCI-2021-0851920-013021
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 3

Brief 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. 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.

Conditions

Myelodysplastic/Myeloproliferative Neoplasm With Ring Sideroblasts and Thrombocytosis, Not Otherwise Specified; Myelodysplastic/Myeloproliferative Neoplasm, Not Otherwise Specified

Outcome Measures

Primary Outcomes (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).

  8 weeks

Secondary Outcomes (5)

• Incidence of Adverse Events (AEs)

  3 months, 29 days

• Duration of Response

  69 days

• Time to Leukemic Transformation

  6 months

• Leukemia-free Survival

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

• Overall Survival

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

Study Arms (2)

Cohort A (luspatercept)

EXPERIMENTAL

Patients 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.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Biological: Luspatercept; Other: Questionnaire Administration

Cohort A (luspatercept, hydroxyurea)

EXPERIMENTAL

Patients 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.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Hydroxyurea; Biological: Luspatercept; Other: Questionnaire Administration

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Cohort A (luspatercept); Cohort A (luspatercept, hydroxyurea)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow biopsy and aspirate

Cohort A (luspatercept); Cohort A (luspatercept, hydroxyurea)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy and aspirate

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Cohort A (luspatercept); Cohort A (luspatercept, hydroxyurea)

Hydroxyurea DRUG

Given PO

Also known as: Droxia, Hydrea, Hydroxycarbamide, Litalir, Onco-Carbide, Oncocarbide, Oxeron, SQ 1089, SQ-1089, Syrea, WR 83799

Cohort A (luspatercept, hydroxyurea)

Luspatercept BIOLOGICAL

Given SC

Also known as: ACE-536, Luspatercept-aamt, Reblozyl

Cohort A (luspatercept); Cohort A (luspatercept, hydroxyurea)

Questionnaire Administration OTHER

Ancillary studies

Cohort A (luspatercept); Cohort A (luspatercept, hydroxyurea)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (3)

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (1)

• 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.

  PMID: 37345627 DERIVED

Related Links

• Mayo Clinic Clinical Trials

MeSH Terms

Conditions

Thrombocytosis; Myeloproliferative Disorders

Interventions

Specimen Handling; Biopsy; Hydroxyurea; luspatercept

Condition Hierarchy (Ancestors)

Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Urea; Amides; Organic Chemicals

Results Point of Contact

• Title: Abhishek Mangaonkar
• Organization: Mayo Clinic

Mangaonkar.Abhishek@mayo.edu

507-538-0173

Study Officials

• Abhishek A. Mangaonkar, M.B.B.S.

  Mayo Clinic in Rochester

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2021
• First Posted: August 13, 2021
• Study Start: February 20, 2023
• Primary Completion: April 17, 2023
• Study Completion: June 17, 2023
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-09

Locations

US (3)