This phase I/II trial studies the side effects and the best dose of ruxolitinib given in combination with recombinant human chorionic gonadotropin and corticosteroids for the treatment of lower gastrointestinal (GI) acute graft versus host disease (aGVHD) in patients who have undergone hematopoietic cell transplant (HCT). GVHD occurs when the donor cells (the graft) see the patient’s body cells (the host) as foreign and attacks them. Acute GVHD occurs within the first few months after the transplant. It is characterized by excess inflammation and may affect the skin (rash, itching), the GI tract (severe diarrhea, pain, ulcers of the GI tract,) and/or the liver (yellowing of the skin, worsening of liver function as detected by blood tests). Drugs that suppress the immune system are routinely given after transplant but are not always effective in preventing GVHD. The standard treatment for acute GVHD high dose steroids, but steroids completely resolve GVHD symptoms in only approximately half of patients. Ruxolitinib is a kinase inhibitor that specifically binds to and inhibits protein tyrosine kinases JAK 1 and 2, which may lead to a reduction of inflammation in GVHD that does not respond to treatment with steroids (refractory). Epidermal growth factors (EGFs), which are involved in the healing of damaged intestinal mucosal tissues, have also been found to be very low in patients with aGVHD. Administration of EGF has been shown to induce remission of other life-threatening forms of intestinal inflammation, such as necrotizing enterocolitis and inflammatory bowel disease. A readily available and inexpensive source of EGF is recombinant human chorionic gonadotropin. Giving ruxolitinib in combination with recombinant human chorionic gonadotropin and corticosteroids may help to minimize the need for high-dose steroids and treat lower GI aGVHD in patients who have undergone HCT.
Additional locations may be listed on ClinicalTrials.gov for NCT05123040.
Locations matching your search criteria
United States
Minnesota
Minneapolis
University of Minnesota/Masonic Cancer CenterStatus: Active
Contact: Punita Grover
Phone: 612-625-8942
PRIMARY OBJECTIVES:
I. To determine the lowest possible recommended phase II dose (RP2D) of corticosteroids when given in combination with ruxolitinib and urinary-derived human chorionic gonadotrophin/epidermal growth factor (uhCG/EGF) in pediatric (over 12 years of age) and adult patients with lower gastrointestinal aGVHD. (Phase I)
II. To determine the proportions of complete, partial, mixed, and no response among surviving patients at days 28 after initiation of protocol therapy in pediatric and adult patients with lower gastrointestinal aGVHD. (Phase II)
SECONDARY OBJECTIVES:
I. To determine the safety and feasibility of steroid dose de-escalation when used in novel combination with ruxolitinib and uhCG/EGF in lower gastrointestinal aGVHD.
II. To determine the incidence of acute GVHD flare after complete response (CR)/partial response (PR) requiring increase of steroids or other systemic treatment at days 28 and 56.
III. To compare the rate of treatment failure for acute GVHD at days 28 and 56 after initiation of protocol therapy to historical controls.
IV. To determine 1-year overall survival and non-relapse mortality.
V. To assess patient quality of life on study.
VI. To collect blood samples and rectosigmoid biopsies for future correlative studies.
OUTLINE:
Patients receive ruxolitinib orally (PO) twice daily (BID) for 56 days followed by dose taper during weeks 9-10 and frequency taper of once daily (QD) during weeks 11-12 in the absence of disease progression or unacceptable toxicity. Patients also recieve recombinant human chorionic gonadotropin subcutaneously (SC) every other day for 3 doses and twice weekly for 14 doses through day 56, as well as prednisone PO or intravenously (IV) or methylprednisolone IV for 56 days in the absence of disease progression or unacceptable toxicity. Patients may undergo echocardiography (ECHO) or multigated acquisition (MUGA) scan at baseline. Patients also undergo collection of blood samples at baseline, weeks 1-6 and 8 of study treatment, and 6 month follow-up. Patients may undergo rectosigmoid biopsy during week 4 of study treatment.
After completion of the study treatment, patients are followed up to 30 days and at 6 months.
Lead OrganizationUniversity of Minnesota/Masonic Cancer Center
Principal InvestigatorPunita Grover
