Hematopoietic and Lymphoid Cell NeoplasmEarly Phase 1NCT04744116
Addition of Cord Blood Tissue-Derived Mesenchymal Stromal Cells to Ruxolitinib for the Treatment of Steroid-Refractory Acute Graft Versus Host Disease
A Early Phase 1 study testing Cellular Therapy and Ruxolitinib in people with Hematopoietic and Lymphoid Cell Neoplasm and Steroid Refractory Graft Versus Host Disease, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 12 to 80 years
- Conditions the study is for
- Hematopoietic and Lymphoid Cell Neoplasm, Steroid Refractory Graft Versus Host Disease
- What is being tested?
- Cellular Therapy and Ruxolitinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Feb 2021to 31 Mar 2032
- Phase
- Early Phase 1
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 12 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Participants between the ages of 12 years and 80 years (inclusive).
- 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.
- Karnofsky/Lansky Performance score of at least 30 at the time of study entry.
- Participants who are women of childbearing potential, must be non-pregnant, not breast-feeding, and use adequate contraception. Male patients must use adequate contraception
- Participants (or legal representative where appropriate) must be capable of providing written informed consent, and assent if indicated.
Who cannot join
- De novo chronic GVHD
- Isolated acute GVHD of skin
- Secondary systemic therapy for acute GVHD ruxolitinib greater than 96 hours before initiation of therapy.
- Primary treatment with agents other than alpha-1 antitrypsin (AAT) glucocorticoids and ruxolitinib.
- 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.
- 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.
- Participants with significant supplemental oxygen requirement defined as >6 L oxygen by nasal cannula.
- Participants with known allergy to bovine or porcine products.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
M D Anderson Cancer Center
Houston, Texas, 77030
Partow Kebriaei, MD, 713-745-0663, pkebriae@mdanderson.org
Partow Kebriaei, MD
About this study
Official title: 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.
Read the detailed description
PRIMARY OBJECTIVE:
- 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.
- Being tested
- Cellular Therapy, Ruxolitinib
- Medical subject headings
- Hematologic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cellular TherapyOther
Also called Cell Therapy
Given ds-MSCs IV
RuxolitinibDrug
Also called INCB-18424, INCB18424, Jakafi, Oral JAK Inhibitor INCB18424
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 (ruxolitinib) | Active comparator | 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. Receives: Drug: Ruxolitinib |
| Arm 2 (ruxolitinib, lower dose ds-MSCs) | Experimental | 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. Receives: Other: Cellular Therapy; Drug: Ruxolitinib |
| Arm 3 (ruxolitinib, higher dose ds-MSCs) | Experimental | 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. Receives: Other: Cellular Therapy; Drug: Ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Death from any cause
Measured: 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.
Measured: At day 28 from start of therapy on study
Incidence of adverse events
Measured: Within 28 days from the start of active study treatment
Secondary outcomes (19)
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).
Measured: 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.
Measured: At days 7, 14, 21 and 28 post treatment
Time to complete response
Will be estimated by the method of Kaplan and Meier.
Measured: Up to 6 months
Time to very good partial response
Will be estimated by the method of Kaplan and Meier.
Measured: Up to 6 months
Time to partial response
Will be estimated by the method of Kaplan and Meier.
Measured: Up to 6 months
Incidence of complete response for each organ
Measured: Up to 6 months
Incidence of very good partial response for each organ
Measured: Up to 6 months
Incidence of partial response for each organ
Measured: Up to 6 months
Durability of organ response
Measured: Up to 6 months
Cumulative incidence of non-relapse mortality (NRM)
Measured: At 6 months post treatment
Cumulative incidence of relapse/progression of the primary disease
Measured: At 6 months
Overall survival
Measured: From enrollment to death from any cause, assessed at 6 months
Disease-free survival
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Up to 28 days after completing last MSC infusion study drug
Incidence of any grade cytokine release
Measured: Up to 28 days after completing last MSC infusion study drug
Incidence of any infusional toxicity
Measured: Within 24 hours of each cord blood-MSC infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Feb 2021
- Study start17 Feb 2021
- Primary completion31 Mar 2032 (estimated)
- Study completion31 Mar 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hematopoietic and Lymphoid Cell NeoplasmStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Partow Kebriaei, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04744116
- Sponsor's protocol ID
- 2019-1122
- Other IDs
- NCI-2020-13889, 2019-1122, P01CA148600
- Status last verified
- Sep 2026
- First submitted
- 3 Feb 2021
- Last updated
- 23 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No