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

University of Minnesota (UMN)

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Acute-graft-versus-host Disease

Treatments: Drug: Ruxolitinib 10 MG Oral Tablet; Drug: hCG; Drug: Corticosteroids

Study type: Interventional

Funder types: Other

Identifiers

NCT05123040

MT2020-28 (Other Identifier)

2020LS098

Details and patient eligibility

About

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.

Enrollment: 55 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

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/ml tested 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 by Viracor. 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 12 through 17-year-olds).

Exclusion criteria

• Progressive malignancy
• Uncontrolled bacterial, fungal, parasitic, or viral infection at initiation of protocol 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, or anti-androgens
• History of a hormone responsive malignancy
• Current thromboembolic disease requiring full-dose anticoagulation - patients receiving pharmacologic prophylaxis for thromboembolic disease will be eligible
• Active or recent (within prior 3 months) thrombus, irrespective of anticoagulation status
• Pregnancy
• Women or men of childbearing potential unwilling to take adequate precautions to avoid unintended pregnancy from the start of protocol treatment through 30 days after the last treatment

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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55 participants in 1 patient group

Ruxolitinib;hCG (Pregnyl®) ;Corticosteroids

Experimental group

Description:

* Ruxolitinib 10 mg by mouth twice daily (with dose adjustments as indicated) through day 56, followed by taper * hCG (Pregnyl®) 2,000 units/m2 SQ every other day x 3 doses, followed by twice weekly x 14 doses (total 17 doses through day 56) * Corticosteroids (Prednisone, or IV methylprednisolone equivalent) * Dose level 1 (starting dose) = 1 mg/kg * Dose level 2 = 0.5 mg/kg * Dose level 3 = 0.25 mg/kg * Dose level 4 = 0.1 mg/kg * Dose level 5 = 0 mg/kg

Treatment:

Drug: Corticosteroids

Drug: hCG

Drug: Ruxolitinib 10 MG Oral Tablet