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Myelodysplastic SyndromesPhase 1/2NCT04539236

Luspatercept and Lenalidomide (L2) in Lower-risk, Non-del(5q) MDS Patients

A Phase 1/2 study testing Lenalidomide and Luspatercept in people with Myelodysplastic Syndromes, run by Mikkael Sekeres, MD at 5 sites in United States.

Suspended

Paused. Enrolment is on hold for now and may resume.

Official record
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Trial summary

The purpose of this study is to evaluate if the combination of drugs, Lenalidomide and Luspatercept, will help improve the treatment of anemia in patients with lower-risk Myelodysplastic Syndrome (MDS). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelodysplastic Syndromes
What is being tested?
Lenalidomide and Luspatercept
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
5 sitesUnited States
Study dates
9 Nov 2021to 1 Aug 2029
Phase
Phase 1/2
Are there results?
None posted in the registry

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

  • Subject is ≥ 18 years of age the time of signing the informed consent form (ICF).
  • Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
  • Documented diagnosis of MDS according to World Health Organization (WHO) / French-American-British (FAB) classification that meets International Prognostic Scoring System Revised (IPSS-R) classification (Greenberg, 2012) of very low, low, or intermediate risk disease; intermediate patients must have a blast percentage <5% to be enrolled.
  • Subjects can be ESA-naïve, or refractory or intolerant to, or ineligible for, prior ESA treatment, as defined by any one of the following:
  • Refractory to prior ESA treatment - documentation of non-response or response that is no longer maintained to prior ESA-containing regimen, either as single agent or combination (eg, with G-CSF); ESA regimen must have been either:
  • recombinant human erythropoietin (rHu EPO) ≥ 40,000 IU/wk for at least 8 doses or equivalent; OR
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  • darbepoetin alpha ≥ 200-500 μg Q1-3W for at least 4 doses or equivalent;
  • Intolerant to prior ESA treatment - documentation of discontinuation of prior ESAcontaining regimen, either as single agent or combination (eg, with G-CSF), at any time after introduction due to intolerance or an adverse event
  • ESA ineligible - Low chance of response to ESA based on endogenous serum erythropoietin level > 200 U/L for subjects not previously treated with ESAs
  • If previously treated with ESAs, agents must have been discontinued ≥ 4 weeks prior to date of C1D1.
  • Requires RBC transfusions, as documented by the following criteria:
  • average transfusion requirement of ≥ 2 units/8 weeks of packed Red Blood Cells (pRBC)s preceding C1D1.
  • Hemoglobin levels at the time of or within 7 days prior to administration of a RBC transfusion must have been ≤ 10.0 g/dL for the transfusion to be counted towards meeting eligibility criteria. Red blood cell transfusions administered when Hgb levels were > 10.0 g/dL and/or RBC transfusions administered for elective surgery will not qualify as a required transfusion for the purpose of meeting eligibility criteria.
  • Eastern Cooperative Oncology Group (ECOG) score of 0, 1, or 2 (Appendix 1)
  • Females of childbearing potential (FCBP), defined as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) 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), must:
  • Have two negative pregnancy tests (urine or serum) as verified by the Investigator prior to starting study therapy (unless the screening pregnancy test was done within 72 hours of C1D1). She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment.
  • If sexually active, agree to use, and be able to comply with, highly effective contraception without interruption, 5 weeks prior to starting investigational product, during the study therapy (including dose interruptions), and for 12 weeks after discontinuation of study therapy.
  • Male subjects must:
  • Agree to use a condom, defined as a male latex condom or nonlatex condom NOT made out of natural (animal) membrane (for example, polyurethane), 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 12 weeks following investigational product discontinuation, even if he has undergone a successful vasectomy.
  • Subject must have a negative Coronavirus Disease of 2019 (COVID-19) test completed ≤7 days prior to administration of protocol therapy.
  • Subject is willing and able to adhere to the study visit schedule and other protocol requirements.

Who cannot join

  • Prior therapy with Lenalidomide.
  • Previously treated with either luspatercept (ACE-536) or sotatercept (ACE-011)
  • MDS associated with del 5q cytogenetic abnormality
  • Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding
  • iron deficiency to be determined by serum ferritin ≤ 15 μg/L and additional testing if clinically indicated (eg, calculated transferrin saturation [iron/total iron binding capacity ≤ 20%] or bone marrow aspirate stain for iron).
  • Prior allogeneic stem cell transplant
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  • Known history of diagnosis of AML
  • Use of any of the following within 4 weeks prior to C1D1:
  • anticancer cytotoxic chemotherapeutic agent or treatment
  • other RBC hematopoietic growth factors (eg, Interleukin-3)
  • investigational drug or device, or approved therapy for investigational use. If the half-life of the previous investigational product is known, use within 5 times the half-life prior to C1D1 or within 5 weeks, whichever is longer is excluded.
  • Uncontrolled hypertension, defined as repeated elevations of diastolic blood pressure (DBP) ≥ 100 mmHg despite adequate treatment.
  • Prior history of malignancies, other than MDS, unless the subject has been free of the disease (including completion of any active or adjuvant treatment for prior malignancy) for ≥ 1 year. However, subjects with the following history/concurrent conditions involving in situ cancer (or similar) are allowed:
  • Basal or squamous cell carcinoma of the skin
  • Carcinoma in situ of the cervix
  • Carcinoma in situ of the breast
  • Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis (TNM) clinical staging system)
  • Major surgery within 4 weeks prior to C1D1. Subjects must have completely recovered from any previous surgery prior to C1D1
  • History of stroke, deep venous thrombosis (DVT), pulmonary or arterial embolism within 6 months prior to C1D1
  • Pregnant or breastfeeding females
  • Subject has any significant medical condition, laboratory abnormality, psychiatric illness, or is considered vulnerable by local regulations (eg, imprisoned or institutionalized) that, in the opinion of the Investigator, would prevent the subject from participating in the study.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites

  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • University of Miami

    Miami, Florida, 33136

Other trials in United States

About this study

Official title: A Multicenter, Phase Ib/II Study That Combines Luspatercept and Lenalidomide (L2) in Lower-risk, Non-del(5q) MDS Patients

The purpose of this study is to evaluate if the combination of drugs, Lenalidomide and Luspatercept, will help improve the treatment of anemia in patients with lower-risk Myelodysplastic Syndrome (MDS).

Being tested
Lenalidomide, Luspatercept
Keywords
non-del(5q) MDS
Medical subject headings
Myelodysplastic Syndromes

What participants receive

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

  • LenalidomideDrug

    Also called Revlimid

    Administered daily by mouth on a 21 day cycle. Doses will be administered at 2.5 mg, 5 mg and 10 mg.

  • LuspaterceptDrug

    Also called Reblozyl, ActRIIB-IgG, ACE-536, 1373715-00-4

    Administered subcutaneously in the upper arm, thigh and/or abdomen on Day 1 of a 21 day cycle. Starting dose will be at 1.0 mg/kg and can be titrated, dependent on participant response, to doses of 1.33 mg/kg, and 1.75 mg/kg.

Study groups in NCT04539236
Study groupRoleWhat they receive
Luspatercept + Lenalidomide GroupExperimentalPhase 1B: Luspatercept will be administered at starting dose 1.0 mg/kg and can be titrated to 1.33 and 1.75 mg/kg dependent on participant response. Lenalidomide will be administered in a dose escalation design between 3 cohorts to determine MTD (2.5 mg, 5 mg and 10 mg daily dose on a 21-day cycle). MTD will be defined as the dose level with 0 or 1 DLT out of 6 participants. MTD will be declared as the RP2D for the Phase II portion of the study. Phase II: Luspatercept will be administered at 1.0 mg/kg and can be titrated to 1.33 and 1.75 mg/kg dependent on participant response. Lenalidomide will be administered with the RP2D daily for 21 days on a 21 day cycle. Treatment with combination of Lenalidomide and Luspatercept will continue as long as a participant is deriving clinical benefit, in the opinion of the treating physician, for up to 5 years or until disease progression or treatment intolerance.
Receives: Drug: Lenalidomide; Drug: Luspatercept

What is being measured

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

  1. MTD/RP2D of Luspatercept combined with Lenalidomide

    Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) of Luspatercept combined with Lenalidomide (reported in mg/kg) from Phase Ib portion of study

    Measured: Up to 15 weeks

  2. DLT Rate for Phase Ib

    DLT rate is defined as the percentage of participants with Dose Limiting Toxicities (DLT) as evaluated by treating physician using the National Cancer Center (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. DLTs are non-hematologic events grade 3 or higher that are at least possibly related to the investigational product and do not resolve to grade 1 or lower within 21 days.

    Measured: Up to 15 weeks

  3. Percentage of participants with RBC-TI response

    Red Blood Cell Transfusion Independence (RBC-TI) response is defined as participants who are RBC transfusion free over any consecutive 56-day period

    Measured: Up to 5 years

  4. Toxicity Rate for Phase II

    Toxicity rate is defined as the percentage of participants with treatment emergent adverse events (TE-AEs) as evaluated by treating physician using the National Cancer Center (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

    Measured: Up to 5 years

Secondary outcomes (8)

  1. Percentage of participants with relevant reduction in RBC transfusion requirement

    Participants with relevant reduction in RBC transfusion requirement will be defined as those participants whose total number of RBC units transfused has decreased by at least 4 units compared to the number transfused during the 8 weeks before study participation

    Measured: Up to 5 years

  2. Percentage of participants with Erythroid Response

    Hematologic Improvement Erythroid Response (HI-E) will bdefined as at least a 1.5 g/dl increase in serum hemoglobin from baseline

    Measured: Up to 5 years

  3. Duration of RBC-TI

    The length of time where participants are RBC transfusion free will be reported

    Measured: Up to 5 years

  4. Percentage of participants with Platelet Response

    Hematologic improvement Platelet response (HI-P) will be defined as:

    For participants with a serum baseline platelet count of > 20,000/mm3 at baseline: An absolute increase of ≥ 30,000/mm3 from baseline

    For participants with a serum platelet count ≤ 20,000/mm3 at baseline: An increase of at least 100% from baseline counts to a platelet count > 20,000/mm3.

    Measured: Up to 5 years

  5. Percentage of participants with Neutrophil Response

    Hematologic improvement of Neutrophil Response (HI-N) will be defined as a serum absolute neutrophil count (ANC) increase from baseline of at least 100%, and an absolute increase of > 500/mm3 from baseline.

    Measured: Up to 5 years

  6. Percentage of participants experiencing a progression to higher-risk MDS or AML

    Percentage of participants experiencing a progression to higher-risk Myelodysplastic Syndrome (MDS) or Acute Myeloid Leukemia (AML)

    Measured: Up to 5 years

  7. Overall Survival (OS)

    OS is calculated for all participants from the date of initial registration to date of death due to any cause. The follow-up for participants last known to be alive is censored at the date of last contact.

    Measured: Up to 5 years

  8. Percentage of participants with RBC-TI lasting 16 weeks

    Percentage of participants with RBC-TI lasting 16 weeks (112 days) will be assessed per the Blood 2019 position paper on defining response in lower-risk MDS

    Measured: Up to 5 years

Timeline

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

  1. First posted4 Sep 2020
  2. Study start9 Nov 2021
  3. Primary completion1 Aug 2029 (estimated)
  4. Study completion1 Aug 2029 (estimated)

Why it stopped: Funding Sponsor decision

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04539236
Sponsor's protocol ID
20201503
Other IDs
CASE2920
Status last verified
Jul 2026
First submitted
31 Aug 2020
Last updated
17 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Lenalidomide and Luspatercept in people with Myelodysplastic Syndromes, run by Mikkael Sekeres, MD at 5 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 21 inclusion and 21 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: paused, as of the sponsor's last update on 17 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Results are not available in the source record.

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?

MTD/RP2D of Luspatercept combined with Lenalidomide (time frame: Up to 15 weeks). The study lists 4 primary outcomes in all. 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 NCT04539236.

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 17 Jul 2026.

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