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RecruitingInterventionalEarly Phase 1

A Randomized Controlled Pilot Study of Two Doses of Cord Blood Tissue-Derived Mesenchymal Stromal Cells Combined With Ruxolitinib Versus Ruxolitinib Alone for Therapy of Steroid-Refractory Acute Graft Versus Host Disease

NCT ID: NCT04744116Sponsor: M.D. Anderson Cancer CenterLast updated: 2026-05-05

Summary

This early phase I trial is to find out the effect of adding cord blood tissue-derived mesenchymal stromal cells (cb-MSCs) to ruxolitinib in treating patients with acute graft versus host disease that does not respond to steroid therapy (steroid-refractory). Ruxolitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. cb-MSCs are a type of tissue helper cell that can be removed from donated umbilical cord blood tissue and grown into many different cell types that can be used to treat cancer and other disease, such as graft versus host disease. This trial aims to learn if adding cb-MSCs to ruxolitinib may help control steroid-refractory acute graft versus host disease.

Detailed description

PRIMARY OBJECTIVE: I. To estimate between-arm differences (Arm 3 versus \[vs\] Arm 1, and Arm 2 vs Arm 1) for each of the 28-day co-primary outcome probabilities. OUTLINE: Patients are randomized to 1 of 3 arms. ARM 1: Patients receive ruxolitinib orally (PO) twice daily (BID) for at least 3 days and may consider tapering after 6 months of therapy if response occurs and therapeutic corticosteroid doses have been discontinued. ARM 2: Patients receive ruxolitinib PO BID as in Arm 1. Patients also receive lower dose of cb-MSCs intravenously (IV) for up to 60 minutes twice weekly (at least 3 days apart) over 4 consecutive weeks for 8 total doses. ARM 3: Patients receive ruxolitinib PO BID as in Arm 1. Patients also receive higher dose of cb-MSCs IV for up to 60 minutes twice weekly (at least 3 days apart) over 4 consecutive weeks for 8 total doses. After completion of study treatment, patients are followed up on day 28 and then for up to 6 months.

Arms & interventions

  • OtherCellular Therapy

    Given ds-MSCs IV

  • DrugRuxolitinib

    Given PO

Outcome measures

Primary

  • Death from any cause

    Time frame: Within 28 days from the start of active study treatment

  • Response

    Will compare the patient's 28-day graft versus host disease (GVHD) status to the patient's baseline GVHD status when steroid refractory acute GVHD was diagnosed.

    Time frame: At day 28 from start of therapy on study

  • Incidence of adverse events

    Time frame: Within 28 days from the start of active study treatment

Secondary

  • Graft versus host disease status

    Time frame: At days 7, 14, 21 and 28 post treatment

  • Proportion of response

    Time frame: At days 7, 14, 21 and 28 post treatment

  • Time to complete response

    Time frame: Up to 6 months

  • Time to very good partial response

    Time frame: Up to 6 months

  • Time to partial response

    Time frame: Up to 6 months

  • Incidence of complete response for each organ

    Time frame: Up to 6 months

  • Incidence of very good partial response for each organ

    Time frame: Up to 6 months

  • Incidence of partial response for each organ

    Time frame: Up to 6 months

  • Durability of organ response

    Time frame: Up to 6 months

  • Cumulative incidence of non-relapse mortality (NRM)

    Time frame: At 6 months post treatment

  • Cumulative incidence of relapse/progression of the primary disease

    Time frame: At 6 months

  • Overall survival

    Time frame: From enrollment to death from any cause, assessed at 6 months

  • Disease-free survival

    Time frame: From enrollment to death from any cause or relapse/progression of the primary disease, assessed at 6 months

  • Graft versus host disease-free survival

    Time frame: At 6 months

  • Incidence of chronic graft versus host disease

    Time frame: At 6 months after first mesenchymal stromal cells (MSC) infusion

  • Incidence of systemic infections

    Time frame: 28 days after last study drug

  • Incidence of toxicities

    Time frame: Up to 28 days after completing last MSC infusion study drug

  • Incidence of any grade cytokine release

    Time frame: Up to 28 days after completing last MSC infusion study drug

  • Incidence of any infusional toxicity

    Time frame: Within 24 hours of each cord blood-MSC infusion

Eligibility criteria

Sex: AllAge: 12 Years to 80 YearsHealthy volunteers: No
Inclusion Criteria: 1. Participants between the ages of 12 years and 80 years (inclusive). 2. Steroid refractory grades II-IV acute GVHD of the Lower GI tract or Liver (including those developing these manifestations after previous acute GVHD of skin) secondary to allogeneic HCT or donor lymphocyte infusion. (Grading, see Appendix I) GVHD with: No improvement after treatment with methylprednisolone at ≥ 2.0 mg/kg/day or equivalent for minimum 7 days, or progressive symptoms after minimum 3 days, or a flare in acute GVHD while on systemic steroids. Participants must have had a biopsy that suggests GVHD; a repeat biopsy to enroll on the study is not necessary. 3. Karnofsky/Lansky Performance score of at least 30 at the time of study entry. 4. Participants who are women of childbearing potential, must be non-pregnant, not breast-feeding, and use adequate contraception. Male patients must use adequate contraception 5. Participants (or legal representative where appropriate) must be capable of providing written informed consent, and assent if indicated. Exclusion Criteria: 1. De novo chronic GVHD 2. Isolated acute GVHD of skin 3. Secondary systemic therapy for acute GVHD ruxolitinib greater than 96 hours before initiation of therapy. 4. Primary treatment with agents other than alpha-1 antitrypsin (AAT) glucocorticoids and ruxolitinib. 5. Participants with uncontrolled infections will be excluded. Infections are considered controlled if appropriate therapy has been instituted and, at the time of enrollment, no signs of progression are present. Progression of infection is defined as hemodynamic instability attributable to sepsis, new symptoms, worsening physical signs or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection. 6. Adult and pediatric patients with cognitive impairments and/or any serious unstable pre-existing medical condition or psychiatric disorder that can interfere with safety or with obtaining informed consent or compliance with study procedures. 7. Participants with significant supplemental oxygen requirement defined as \>6 L oxygen by nasal cannula. 8. Participants with known allergy to bovine or porcine products.

Study locations (1)

M D Anderson Cancer Center

Houston, Texas, 77030

Recruiting
Partow Kebriaei, MD · Contact
Partow Kebriaei, MD · Principal Investigator