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

NCT05123040 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: 2020LS098MT2020-28
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute-graft-versus-host Disease

Keywords

aGVHD

Outcome Measures

Primary Outcomes (2)

• Recommend the lowest possible dose for Phase II of corticosteroids when given in combination with ruxolitinib and uhCG/EGF in pediatric based on DLT frequency

  Plan report patients proportions and their 95% confidence intervals of paitents who experience dose limiting toxicity. Determine best dose based on DLT criteria by CTCAE v5.0 * Thrombosis requiring anticoagulation * Ascites (grade 3-5) * Ovarian hyperstimulation syndrome

  28 days after therapy

• Best response of treatment in adult and children

  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 Minnesota high-risk aGVHD

  28 days after therapy

Secondary Outcomes (9)

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

  30 days after treatment

• Incidence of acute GVHD flare after CR/PR requiring increase of steroids or other systemic treatment

  28 days after treatment

• Incidence of acute GVHD flare after CR/PR requiring increase of steroids or other systemic treatment

  56 days after treatment

• Compare the rate of treatment failure for acute GVHD after initiation of protocol therapy to historical controls

  28 days after treatment

• Compare the rate of treatment failure for acute GVHD after initiation of protocol therapy to historical controls

  56 days after treatment

Study Arms (1)

Ruxolitinib;hCG (Pregnyl®) ;Corticosteroids

EXPERIMENTAL

* 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

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

Interventions

Ruxolitinib 10 MG Oral Tablet DRUG

By mouth twice daily through day 56, then tapered

Ruxolitinib;hCG (Pregnyl®) ;Corticosteroids

hCG DRUG

2,000 units/m2 SQ every other day x 3 doses, followed by twice weekly x 14 doses

Also known as: Pregnyl

Ruxolitinib;hCG (Pregnyl®) ;Corticosteroids

Corticosteroids DRUG

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 • If dose level 1 is determined to be below the Recommended Phase 2 Dose (RP2D), the dose will be escalated: * Dose level -1 = 1.5 mg/kg * Dose level -2 = 2 mg/kg

Also known as: Prednisone, IV methylprednisolone

Ruxolitinib;hCG (Pregnyl®) ;Corticosteroids

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center at University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

MeSH Terms

Interventions

ruxolitinib; Chorionic Gonadotropin; Adrenal Cortex Hormones; Prednisone; Methylprednisolone

Intervention Hierarchy (Ancestors)

Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Placental Hormones; Peptides; Amino Acids, Peptides, and Proteins; Pregnancy Proteins; Proteins; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Prednisolone; Pregnadienetriols

Study Officials

• Sherman Holtan, MD

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2021
• First Posted: November 17, 2021
• Study Start: June 5, 2023
• Primary Completion: February 27, 2026
• Study Completion: February 27, 2026
• Last Updated: March 24, 2026

Record last verified: 2026-03

Locations

US (1)