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
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
Study locations (1)
M D Anderson Cancer Center
Houston, Texas, 77030