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

NCT05998408 | Active Not Recruiting Phase 1 Results FDA Drug

• 2 other identifiers: 10001667001667-H
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Single Lineage Cytopenias, T-LGL; Hypoplastic MDS; Severe Aplastic Anemia

Keywords

Hematologic toxicity; Ruxolitinib

Outcome Measures

Primary Outcomes (2)

• 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

  6 months

• 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

  6 months

Secondary Outcomes (8)

• Hematological Response

  3, 12 months, and yearly thereafter

• Depth of Response

  3, 6 months

• Rate of Clonal Evolution

  Variable

• Rate of Relapse

  Variable

• Time to Transfusion Independence

  Variable

Study Arms (5)

Cohort 1: PParticipants with Severe Aplastic Anemia (SAA)

EXPERIMENTAL

Participants 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.

Drug: Ruxolitinib

Cohort 2: Participants with Moderate Aplastic Anemia (MAA)

EXPERIMENTAL

Participants 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.

Drug: Ruxolitinib

Cohort 3: Participants with Unilineage Bone Marrow Failure Disorder

EXPERIMENTAL

Participants 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.

Drug: Ruxolitinib

Cohort 4: Participants with T-cell large granular lymphocyte (T-LGL) leukemia

EXPERIMENTAL

Participants 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

Drug: Ruxolitinib

Cohort 5: Participants with hypoplastic myelodysplastic syndrome (hMDS)

EXPERIMENTAL

Participants 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.

Drug: Ruxolitinib

Interventions

Ruxolitinib DRUG

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.

Cohort 1: PParticipants with Severe Aplastic Anemia (SAA); Cohort 2: Participants with Moderate Aplastic Anemia (MAA); Cohort 3: Participants with Unilineage Bone Marrow Failure Disorder; Cohort 4: Participants with T-cell large granular lymphocyte (T-LGL) leukemia; Cohort 5: Participants with hypoplastic myelodysplastic syndrome (hMDS)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Limitations and Caveats

The clinical trial was discontinued early before enrollment was completed across all cohorts.

Results Point of Contact

• Title: Emma M. Groarke, M.D.
• Organization: National Heart, Lung, and Blood Institute

Emma.Groarke@nih.gov

301.451.7129

Study Officials

• Emma M Groarke, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2023
• First Posted: August 21, 2023
• Study Start: February 20, 2024
• Primary Completion: July 22, 2025
• Study Completion (Estimated): June 3, 2032
• Last Updated: July 15, 2026
• Results First Posted: July 15, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)