Ruxolitinib, Human Chorionic Gonadotropin (uhCG/EGF), and Dose De-escalated Corticosteroids

Phase

1/2

Condition

N/A

Treatment

Ruxolitinib 10 MG Oral Tablet

hCG

Corticosteroids

Clinical Study ID

NCT05123040

2020LS098

MT2020-28

Ages > 12
All Genders

Study Summary

This multi-center center phase I/II study to establish the lowest possible recommended phase 2 dose (RP2D) of corticosteroids in conjunction with ruxolitinib and uhCG/EGF (a novel combination) for high-risk aGVHD.

This is a single arm study designed to determine the lowest dose of corticosteroids required (toxicity endpoint) without impairing GVHD complete response or partial response (CR/PR) at day 28 when given in conjunction with uhCG/EGF and ruxolitinib.

After completion of the corticosteroid dose finding, the final dose will be carried forward into a two-stage phase II extension trial to confirm safety and make a preliminary determination of efficacy of this novel drug combination for high-risk aGVHD.

Eligibility Criteria

Inclusion

Inclusion Criteria:

HCT recipients over 12 years of age within the first 7 days of initial treatment of high-risk aGVHD, defined as:

Newly diagnosed Minnesota high-risk aGVHD -OR-
Newly diagnosed Minnesota standard risk aGVHD with plasma amphiregulin ≥ 33 pg/mltested at the UMN Cytokine Reference Lab. For amphiregulin lab ordering information,see Fairview Lab Guide:http://labguide.fairview.org/showtest.asp?testid=6766&format=long -OR-
Newly diagnosed Minnesota standard risk aGVHD Ann Arbor 3 biomarkers tested byViracor. For ordering information, see:https://www.viracor-eurofins.com/test-menu/403572p-agvhd-symptomatic-onset-algorithm/
Renal: Serum creatinine ≤2.5x upper limit of normal (ULN)
Cardiac: Left ventricular ejection fraction (LVEF) ≥ 35%
Voluntary written consent (adult or parent/guardian with minor assent for 12through 17-year-olds).

Exclusion

Exclusion Criteria:

Progressive malignancy
Uncontrolled bacterial, fungal, parasitic, or viral infection at initiation ofprotocol treatment
Unwilling or unable to stop supplemental sex hormone therapy (estrogen,progesterone, and/or testosterone preparations)
Unwilling or unable to stop GnRH antagonists, aromatase inhibitors, oranti-androgens
History of a hormone responsive malignancy
Current thromboembolic disease requiring full-dose anticoagulation - patientsreceiving pharmacologic prophylaxis for thromboembolic disease will be eligible
Active or recent (within prior 3 months) thrombus, irrespective of anticoagulationstatus
Pregnancy
Women or men of childbearing potential unwilling to take adequate precautions toavoid unintended pregnancy from the start of protocol treatment through 30 daysafter the last treatment

Study Design