Clinical trial NCT04744116: Addition of Cord Blood Tissue-Derived Mesenchymal Stromal Cells to Ruxolitinib for the Treatment of Steroid-Refractory Acute Graft Versus Host Disease
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Hematopoietic and Lymphoid Cell Neoplasm
Steroid Refractory Graft Versus Host Disease
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2021-02-08
Enrollment: 24
Sex: ALL
Minimum age (years): 12
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Death from any cause
timeFrame: Within 28 days from the start of active study treatment
measure: Response
timeFrame: At day 28 from start of therapy on study
measure: Incidence of adverse events
timeFrame: Within 28 days from the start of active study treatment
Secondary outcomes:
measure: Graft versus host disease status
timeFrame: At days 7, 14, 21 and 28 post treatment
measure: Proportion of response
timeFrame: At days 7, 14, 21 and 28 post treatment
measure: Time to complete response
timeFrame: Up to 6 months
measure: Time to very good partial response
timeFrame: Up to 6 months
measure: Time to partial response
timeFrame: Up to 6 months
measure: Incidence of complete response for each organ
timeFrame: Up to 6 months
measure: Incidence of very good partial response for each organ
timeFrame: Up to 6 months
measure: Incidence of partial response for each organ
timeFrame: Up to 6 months
measure: Durability of organ response
timeFrame: Up to 6 months
measure: Cumulative incidence of non-relapse mortality (NRM)
timeFrame: At 6 months post treatment
measure: Cumulative incidence of relapse/progression of the primary disease
timeFrame: At 6 months
measure: Overall survival
timeFrame: From enrollment to death from any cause, assessed at 6 months
measure: Disease-free survival
timeFrame: From enrollment to death from any cause or relapse/progression of the primary disease, assessed at 6 months
measure: Graft versus host disease-free survival
timeFrame: At 6 months
measure: Incidence of chronic graft versus host disease
timeFrame: At 6 months after first mesenchymal stromal cells (MSC) infusion
measure: Incidence of systemic infections
timeFrame: 28 days after last study drug
measure: Incidence of toxicities
timeFrame: Up to 28 days after completing last MSC infusion study drug
measure: Incidence of any grade cytokine release
timeFrame: Up to 28 days after completing last MSC infusion study drug
measure: Incidence of any infusional toxicity
timeFrame: Within 24 hours of each cord blood-MSC infusion
Other outcomes:
measure: Cytokine biomarker analysis (optional)
timeFrame: Up to 6 months
measure: Fecal samples analysis (optional)
timeFrame: Up to 6 months
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Partow Kebriaei, MD
role: PRINCIPAL_INVESTIGATOR
References: