Addition of Cord Blood Tissue-Derived Mesenchymal Stromal Cells to Ruxolitinib for the Treatment of Steroid-Refractory Acute Graft Versus Host Disease

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

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.

Study Overview

• Status: Recruiting
• Conditions: Hematopoietic and Lymphoid Cell Neoplasm; Steroid Refractory Graft Versus Host Disease
• Intervention / Treatment: Drug: Ruxolitinib; Other: Cellular Therapy

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.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Partow Kebriaei, MD; Phone Number: 713-745-0663; Email: pkebriae@mdanderson.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • M D Anderson Cancer Center
      • Contact: Partow Kebriaei, MD; Phone Number: 713-745-0663; Email: pkebriae@mdanderson.org
      • Principal Investigator: Partow Kebriaei, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1 (ruxolitinib); Patients receive ruxolitinib PO 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.	Drug: Ruxolitinib; Given PO; Other Names: Jakafi; INCB-18424; INCB18424; Oral JAK Inhibitor INCB18424
Experimental: Arm 2 (ruxolitinib, lower dose ds-MSCs); Patients receive ruxolitinib PO BID as in Arm 1. Patients also receive lower 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.	Drug: Ruxolitinib; Given PO; Other Names: Jakafi; INCB-18424; INCB18424; Oral JAK Inhibitor INCB18424; Other: Cellular Therapy; Given ds-MSCs IV; Other Names: Cell Therapy
Experimental: Arm 3 (ruxolitinib, higher dose ds-MSCs); 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.	Drug: Ruxolitinib; Given PO; Other Names: Jakafi; INCB-18424; INCB18424; Oral JAK Inhibitor INCB18424; Other: Cellular Therapy; Given ds-MSCs IV; Other Names: Cell Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Death from any cause		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.	At day 28 from start of therapy on study
Incidence of adverse events		Within 28 days from the start of active study treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Graft versus host disease status	Will assess complete response (CR), very good partial response (VGPR), partial response (PR), stable disease (SD), and progressive disease (PD).	At days 7, 14, 21 and 28 post treatment
Proportion of response	Will assess proportion of patients with CR, PR, VGPR, and no-response (NR). The event NR is defined as stable disease, mixed response, disease progression, OR initiation of additional systemic (second-line) GVHD therapies.	At days 7, 14, 21 and 28 post treatment
Time to complete response	Will be estimated by the method of Kaplan and Meier.	Up to 6 months
Time to very good partial response	Will be estimated by the method of Kaplan and Meier.	Up to 6 months
Time to partial response	Will be estimated by the method of Kaplan and Meier.	Up to 6 months
Incidence of complete response for each organ		Up to 6 months
Incidence of very good partial response for each organ		Up to 6 months
Incidence of partial response for each organ		Up to 6 months
Durability of organ response		Up to 6 months
Cumulative incidence of non-relapse mortality (NRM)		At 6 months post treatment
Cumulative incidence of relapse/progression of the primary disease		At 6 months
Overall survival		From enrollment to death from any cause, assessed at 6 months
Disease-free survival		From enrollment to death from any cause or relapse/progression of the primary disease, assessed at 6 months
Graft versus host disease-free survival	Patients alive, free of active acute or chronic GVHD, and without other systemic agents (or escalation of steroids to >= 2.5 mg/kg/day of prednisone [or methylprednisolone equivalent of 2 mg/kg/day]) added for treatment of GVHD will be considered successes for this endpoint	At 6 months
Incidence of chronic graft versus host disease	Chronic GVHD is defined per National Institutes of Health Consensus Criteria. Diagnosis of chronic GVHD of any severity (mild, moderate, or severe) is considered an event for this endpoint. Organ involvement and maximum severity will also be described at six months.	At 6 months after first mesenchymal stromal cells (MSC) infusion
Incidence of systemic infections	The incidence of grade 2 to 3 systemic infections occurring from study treatment until 28 days after last study drug will be described using standard Common Terminology Criteria for Adverse Events (CTCAE) criteria. Infections will be recorded by site of disease, date of onset, and severity.	28 days after last study drug
Incidence of toxicities	The incidence of grade 3-5 treatment-emergent adverse events (per CTCAE version 5.0) that occur through 28 days after completing last MSC infusion study drug will be described.	Up to 28 days after completing last MSC infusion study drug
Incidence of any grade cytokine release		Up to 28 days after completing last MSC infusion study drug
Incidence of any infusional toxicity		Within 24 hours of each cord blood-MSC infusion

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cytokine biomarker analysis (optional)	Will use cytokine biomarker assays to predict response to therapy.	Up to 6 months
Fecal samples analysis (optional)	Will use fecal samples to assess microbiome and potential predictor for response to therapy.	Up to 6 months

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Partow Kebriaei, MD, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• M D Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2021
• Primary Completion (Estimated): March 31, 2032
• Study Completion (Estimated): March 31, 2032

Study Registration Dates

• First Submitted: February 3, 2021
• First Submitted That Met QC Criteria: February 3, 2021
• First Posted (Actual): February 8, 2021

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: April 29, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Hematologic Neoplasms; Therapeutics; Biological Therapy; ruxolitinib; Cell- and Tissue-Based Therapy
• Other Study ID Numbers: 2019-1122 (Other Identifier: M D Anderson Cancer Center); NCI-2020-13889 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); P01CA148600 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No