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Severe Aplastic AnemiaPhase 1/2NCT05998408

JAK1/2 Inhibitor Ruxolitinib for Relapsed/Refractory Immune Bone Marrow Failure

A Phase 1/2 study testing Ruxolitinib in people with Severe Aplastic Anemia and Single Lineage Cytopenias, T-LGL, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Background: Immune bone marrow failure is a condition that occurs when a person s immune system attacks the cells of the bone marrow. This can lead to diseases including different types of anemias and blood cancers. Some of these diseases can be deadly. Better treatments are needed. Read more about this study

Who is it for?
Ages 18 to 99 years
What is being tested?
Ruxolitinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
1 siteUnited States
Study dates
20 Feb 2024to 3 Jun 2032
Phase
Phase 1/2
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 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants of both sexes will be considered for inclusion in this study. There will be no racial, ethnic, or sex discrimination. To be eligible to participate in the treatment portion of this study, an individual must meet all of the following inclusion criteria and none of the following exclusion criteria:
  • ALL COHORTS:
  • Ability of the participant or legally authorized representative (LAR) to understand and be willing to sign a written informed consent document
  • Age 18 or older
  • For females of childbearing potential, stated willingness to use an accepted method of contraception for the duration of the study. Accepted methods of contraception are:
  • Total abstinence
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  • Use of an implanted or intrauterine hormonal device for at least 30 consecutive days before study drug administration
  • Use of oral, patch or injectable contraceptives or a vaginal hormonal device for at least 30 consecutive days before study drug infusion
  • Use of a non-hormonal intrauterine device for at least 30 consecutive days before study drug administration
  • Two barrier methods such as a diaphragm with spermicide or a condom with spermicide
  • For sexually active males with a female partner of childbearing potential, stated willingness to agree to use a condom with spermicide for the duration of the study.
  • Diagnosis of immune bone marrow failure (see specific cohort)
  • COHORT 1: RELAPSED/REFRACTORY SAA:
  • Meet all 3 criteria below:
  • Severe aplastic anemia:
  • -Bone marrow cellularity <30% excluding lymphocytes
  • AND
  • At least two of the following:
  • Absolute neutrophil count < 0.5 x 10^9/L
  • Platelet count < 20 x 10^9/L
  • Absolute Reticulocyte count < 60 x 10^9/L
  • Relapsed or refractory disease as evidenced by a course of at least 1 prior therapy.
  • Not suitable for transplant due to age, co-morbidities, lack of suitable donor, or participant choice.
  • Patients who have a documented historic diagnosis of SAA and have received an ATG-based therapy in the past and are now relapsed / refractory may be included in this cohort even if documentation of original CBC and bone marrow are unavailable.
  • COHORT 2: RELAPSED/REFRACTORY MODERATE AA:
  • Moderate AA:
  • Aplastic anemia (hypocellular bone marrow for age) with no evidence for other disease processes causing marrow failure, and depression of at least two out of three blood counts below the normal values but not fulfilling the criteria for SAA:
  • Absolute neutrophil count <= l.2 x 10^9/L
  • Platelet count <= 70 x 10^9/L
  • Anemia with hemoglobin <= 9 g/dL and absolute reticulocyte count < 60 x 10^9/L or transfusion dependence
  • Relapsed or refractory disease as evidenced by a course of at least 1 prior therapy.
  • COHORT 3: RELAPSED/REFRACTORY UNILINEAGE BONE MARROW FAILURE DISORDERS:
  • Cytopenia in lineage as below:
  • -Erythroid lineage: Hemoglobin <= 9 g/dL and reticulocyte count < 60 x 10^9/L or red cell transfusion dependence and bone marrow with absent or reduced red cell precursors
  • OR
  • Platelet lineage: Thrombocytopenia <= 30 x 10^9/L or platelet transfusion dependence and bone marrow with absent or reduced megakaryocytes
  • OR
  • Granulocyte lineage: Neutropenia <= 0.5 x 10^9/L and bone marrow for with absent or reduced granulopoiesis
  • No evidence of viral or drug suppression of the marrow, T-LGL, dysplasia, or underproduction anemias secondary to B12, folate, iron or other reversible causes.
  • Relapsed or refractory disease as evidenced by a course of at least 1 prior therapy.
  • COHORT 4: RELAPSED/REFRACTORY T-LGL WITH CYTOPENIAS:
  • Clinical history supportive of the diagnosis of T-LGL leukemia (i.e., a history of cytopenias with peripheral blood morphologic evidence of LGLs).
  • Immunophenotypic studies of peripheral blood showing an increased population of T-LGLs (suggested by staining with CD3+, CD8+ and CD16+ or CD57+) or gamma-delta T cells.
  • Restricted or clonal rearrangement of the T-cell receptor by PCR
  • AND cytopenia as follows:
  • Severe neutropenia (< 0.5 x 10^9/L);
  • OR
  • Severe thrombocytopenia (<= 20 x 10^9/L), or moderate thrombocytopenia (<= 50 x 10^9/L) with active bleeding;
  • OR
  • Symptomatic anemia with a hemoglobin <= 9 g/dL or red blood cell transfusion dependence
  • -Relapsed or refractory disease as evidenced by a course of at least 1 prior therapy.
  • COHORT 5: HYPOPLASTIC MDS:
  • -A diagnosis of hypoplastic MDS by WHO 2016, WHO 2022, or ICC criteria with significant cytopenias defined as:
  • Bone marrow hypocellular for age
  • AND
  • Either morphologic dysplasia or cytogenetic abnormality
  • AND
  • At least one of the following:
  • Neutropenia: Absolute neutrophil count < 0.5 x 10^9/L
  • Thrombocytopenia: Platelet count < 30 x 10^9/L or platelet transfusion dependence
  • Anemia: Hemoglobin < 9g/dL or red cell transfusion-dependence or absolute reticulocyte count <60 x 10^9/L
  • Relapsed or refractory disease as evidenced by a course of at least 1 prior therapy

Who cannot join

  • An individual who meets any of the following criteria will be excluded from participation in this study:
  • Known diagnosis or high suspicion of constitutional marrow failure syndrome
  • Evidence of a clonal disorder with poor risk cytogenetics per R-IPSS criteria involving chromosome 7 (-7del/-7), chromosome 3 (inv 3/del3/t(3)) or three or more chromosomal abnormalities (complex)
  • MDS with EB-1, EB-2, AML, chronic myelomonocytic leukemia (CMML), MDS/MPN
  • For MDS: Has received hypomethylating agent, chemotherapy, or immunomodulatory therapy within 8 weeks prior to study entry
  • History of progressive multifocal leuko-encephalopathy (PML)
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  • Infection not adequately responding to appropriate therapy
  • Participants with untreated or poorly controlled HIV, Hepatitis B or C
  • Participants with cancer who are on active chemotherapeutic treatment
  • Presence of severely impaired renal function defined by CrCl (as calculated by eGFR) less than 15 mL/min not requiring renal dialysis
  • Current pregnancy, or unwillingness to take oral contraceptives or use a barrier method of birth control or practice abstinence to refrain from pregnancy if of childbearing potential during this study
  • Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease of such severity that it would preclude the participant s ability to tolerate protocol therapy, or that death within 7-10 days is likely
  • Inability to understand the investigational nature of the study or to give informed consent or does not have a legally authorized representative or surrogate that can provide informed consent
  • Hypersensitivity to ruxolitinib or its components
  • Inability to swallow pills
  • Currently breastfeeding
  • Active non-melanoma skin cancer
  • Acute thrombosis (myocardial infarction, ischemic heart disease requiring stents, stroke, pulmonary embolism, or deep venous thrombosis) within the last 6 months
  • Patients with a PNH clone >50% who are not taking anticoagulation or anticomplement therapy

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: A Phase I/II Study of the JAK1/2 Inhibitor Ruxolitinib for Relapsed / Refractory Immune Bone Marrow Failure

Background:

Immune bone marrow failure is a condition that occurs when a person s immune system attacks the cells of the bone marrow. This can lead to diseases including different types of anemias and blood cancers. Some of these diseases can be deadly. Better treatments are needed.

Read more

Objective:

To test a drug (ruxolitinib) in people with different types of immune bone marrow failure.

Eligibility:

Adults aged 18 and older with an immune bone marrow failure.

Design:

Participants will be screened. They will have a physical exam. They will give samples of blood and saliva. They will have a bone marrow biopsy: A large needle will be inserted into a small cut to remove a sample of the soft tissue inside the bone. Some participants may have a skin biopsy: A small piece of skin will be removed. Some may have a computed tomography (CT) scan: They will lie on a table that slides into a donut-shaped machine that uses X-rays to make pictures of the inside of the body.

Ruxolitinib is a tablet taken by mouth. Participants will take the drug twice a day for up to 6 months.

Participants will have blood tests every week while they are taking the drug. These tests can be done by the participant s own physician and the results sent to the researchers.

Participants will have clinic visits after taking the drug for 3 months and 6 months and then after 1, 2, and 3 years. The blood tests and bone marrow biopsy will be repeated.

Participants who improve while taking the drugs may go on to an extension phase of the study.

Read the detailed description

Study Description:

This is a prospective, non-randomized, phase I/II study in which participants with relapsed/refractory immune marrow failure (severe aplastic anemia, moderate aplastic anemia, single lineage cytopenias, T-LGL, and hypoplastic MDS) will be treated with the JAK1/2 inhibitor ruxolitinib. Our hypothesis is that JAK1/2 inhibition with ruxolitinib will result in hematologic improvement in participants with immune marrow failure.

Objectives:

The primary objectives are to assess safety and efficacy of the JAK1/2 inhibitor ruxolitinib in immune marrow failure.

The secondary objectives are to assess early and long-term hematologic response, depth of response, development of transfusion independence, rate of relapse, rate of clonal evolution to myeloid malignancy and Paroxysmal Nocturnal Hemoglobinuria (PNH), 3-year overall survival, response after re-initiation of therapy in relapsed participants, maximum tolerated dose.

Endpoints:

The primary endpoints are: (a) the primary safety endpoint will be number of participants who complete a full course of ruxolitinib without cessation required by hematologic toxicity in the 6 months following treatment initiation; (b) The primary efficacy endpoint is overall response (OR) rate by 6 months.

The secondary endpoints are time to OR, OR at 3 months, development of transfusion independence at 3 and 6 months, type of response at 3 and 6 months, rate of relapse up to 3 years, rate of clonal evolution up to 3 years, 3-year overall survival (OS), and number of participants tolerating maximum ruxolitinib dose.

Being tested
Ruxolitinib
Keywords
Hematologic toxicity, Ruxolitinib
Medical subject headings
Anemia, Aplastic

What participants receive

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

  • RuxolitinibDrug

    Participants will be instructed to take ruxolitinib at up to 20mg (total) BID for up to 6 months (with or without food). The dose will be increased weekly in 5 mg twice-daily increments, up to a maximum dose of 20 mg by mouth twice daily.

Study groups in NCT05998408
Study groupRoleWhat they receive
Cohort 1: PParticipants with Severe Aplastic Anemia (SAA)ExperimentalParticipants diagnosed with Severe Aplastic Anemia (SAA) will be administered ruxolitinib 5 mg by mouth twice daily. The dose will be increased weekly in 5 mg twice-daily increments, up to a maximum dose of 20 mg by mouth twice daily.
Receives: Drug: Ruxolitinib
Cohort 2: Participants with Moderate Aplastic Anemia (MAA)ExperimentalParticipants diagnosed with Moderate Aplastic Anemia (MAA) will be administered ruxolitinib 5 mg by mouth twice daily. The dose will be increased weekly in 5 mg twice-daily increments, up to a maximum dose of 20 mg by mouth twice daily.
Receives: Drug: Ruxolitinib
Cohort 3: Participants with Unilineage Bone Marrow Failure DisorderExperimentalParticipants diagnosed with Unilineage Bone Marrow Failure Disorder will be administered ruxolitinib 5 mg by mouth twice daily. The dose will be increased weekly in 5 mg twice-daily increments, up to a maximum dose of 20 mg by mouth twice daily.
Receives: Drug: Ruxolitinib
Cohort 4: Participants with T-cell large granular lymphocyte (T-LGL) leukemiaExperimentalParticipants diagnosed with T-cell large granular lymphocyte (T-LGL) will be administered ruxolitinib 5 mg by mouth twice daily. The dose will be increased weekly in 5 mg twice-daily increments, up to a maximum dose of 20 mg by mouth twice daily
Receives: Drug: Ruxolitinib
Cohort 5: Participants with hypoplastic myelodysplastic syndrome (hMDS)ExperimentalParticipants diagnosed with hypoplastic myelodysplastic syndrome (hMDS) will be administered ruxolitinib 5 mg by mouth twice daily. The dose will be increased weekly in 5 mg twice-daily increments, up to a maximum dose of 20 mg by mouth twice daily.
Receives: Drug: Ruxolitinib

What is being measured

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

  1. Number of Participants Who Completed a Full Course of Ruxolitinib Without Discontinuation Due to Hematologic Toxicity

    Numbers of participants who complete a full course of ruxolitinib without discontinuation due to hematologic toxicity in the 6 months following treatment initiation. Discontinuation due to hematologic toxicity is defined as those participants that remain off drug for 6 consecutive weeks due to ongoing hematologic toxicity.

    Hematologic toxicity for this study will be defined as follows:

    • Greater than 50% increase in transfusion needs in participants who were transfusion dependent prior to ruxolitinib therapy, lasting for more than 12 weeks
    • Need for any transfusion for more than 12 weeks in participants who were transfusion independent prior to ruxolitinib therapy. This excludes transfusions given for Hb >7g/dL or platelets >10 x 109 or those given for procedures.
    • Worsening in peripheral cytopenias >50% compared to pre-treatment levels in participants with a pre-treatment ANC >500 or platelets >50 Drop in ANC to <200 in participants with a pre-treatment ANC <500

    Measured: 6 months

  2. Number of Participants Who Achieved an Overall Response

    Participants who had a CR at 3 months and discontinued study drug were considered responders, even if they subsequently relapsed.

    • Cohort 1: Response: No Camitta SAA criteria; ≥2 of ANC ≥0.5 × 10⁹/L, platelets ≥20 × 10⁹/L, reticulocytes ≥60 × 10⁹/L on 2 counts ≥1 week apart Complete Response (CR): ANC ≥1 × 10⁹/L, platelets ≥100 × 10⁹/L, Hb ≥10 g/dL Partial Response (PR): Response but not CR
    • Cohorts 3: Response: ≥1 evaluable lineage response Erythroid: Hb ↑ >1.5 g/dL, ≥4 fewer RBC transfusions/8 weeks, or reticulocytes >60 × 10⁹/L Platelet: ↑ ≥30 × 10⁹/L if baseline ≥20 × 10⁹/L, or <20 to >20 × 10⁹/L and ≥100% ↑ Neutrophil: ≥100% ↑ and absolute ↑ >0.5 × 10⁹/L CR: ANC ≥1 × 10⁹/L, platelets ≥100 × 10⁹/L, Hb ≥10 g/dL
    • Cohort 4: Response: ≥1 evaluable lineage response CHR: ANC >1.5 × 10⁹/L, platelets >150 × 10⁹/L, lymphocytes <4 × 10⁹/L PHR: Improvement in ≥1 affected parameter but not CHR CMR: No clonal T-cell detection and CHR CR: CHR and CMR

    Measured: 6 months

Secondary outcomes (8)

  1. Hematological Response

    Measured: 3, 12 months, and yearly thereafter

  2. Depth of Response

    Measured: 3, 6 months

  3. Rate of Clonal Evolution

    Measured: Variable

  4. Rate of Relapse

    Measured: Variable

  5. Time to Transfusion Independence

    Measured: Variable

  6. Overall Survival

    Measured: Variable

  7. Hematological Response of Relapse Subjects That Re-start Treatment

    Measured: Variable

  8. Percent of Patients Tolerating 20 mg Ruxolitinib BID.

    Measured: Variable

Timeline

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

  1. First posted21 Aug 2023
  2. Study start20 Feb 2024
  3. Primary completion22 Jul 2025
  4. Study completion3 Jun 2032 (estimated)

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
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05998408
Sponsor's protocol ID
10001667
Other IDs
001667-H
Status last verified
Sep 2026
First submitted
17 Aug 2023
Last updated
14 Oct 2026
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 Ruxolitinib in people with Severe Aplastic Anemia and Single Lineage Cytopenias, T-LGL, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site 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 62 inclusion and 19 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: under way, not looking for participants, as of the sponsor's last update on 14 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

Yes. Results are posted in the registry (first posted 15 Jul 2026). 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?

Number of Participants Who Completed a Full Course of Ruxolitinib Without Discontinuation Due to Hematologic Toxicity (time frame: 6 months). The study lists 2 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 NCT05998408.

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 14 Oct 2026; AzTrials last refreshed its copy on 7 Nov 2026.

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