What side effects are associated with this type of intervention?

Common treatments for Graft-versus-Host Disease (GVHD) include corticosteroids, ruxolitinib, and uhCG/EGF. Corticosteroids can cause hyperglycemia, hypertension, increased infection risk, osteoporosis, and mood changes. Ruxolitinib, a JAK1/2 inhibitor, may lead to anemia, thrombocytopenia, increased infection risk, and elevated liver enzymes. The combination of uhCG/EGF is still under investigation, with specific side effects not well-documented yet. Broadly, GVHD treatments can have significant side effects impacting multiple organ systems.

What prior FDA approvals exist?

For the treatment of Graft-versus-Host Disease (GVHD), corticosteroids have long been the cornerstone of therapy due to their potent anti-inflammatory effects. Ruxolitinib, a JAK1/2 inhibitor, has also been approved by the FDA for steroid-refractory acute GVHD, offering a targeted approach to modulate the immune response. While uhCG/EGF is still under investigation, its combination with ruxolitinib and corticosteroids represents a novel therapeutic strategy aimed at enhancing anti-inflammatory and regenerative effects. These treatments reflect a broader trend towards integrating targeted immunomodulatory and regenerative therapies in the management of GVHD.

What other types of research exist?

Promising novel alternatives for GVHD treatment in 2024 include: 1) Itacitinib, a selective JAK1 inhibitor, which has shown efficacy in clinical trials. 2) Abatacept, a fusion protein that modulates T-cell activation, recently approved for GVHD prophylaxis. 3) Vedolizumab, an integrin receptor antagonist, which is being explored for its potential in reducing GVHD severity. These alternatives offer targeted mechanisms that may provide effective treatment options for GVHD patients.

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Corticosteroid

Combination Therapy for Graft-versus-Host Disease

Phase 1 & 2

Recruiting

Led By Sherman Holtan, MD

Research Sponsored by Masonic Cancer Center, University of Minnesota

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Renal: Serum creatinine ≤2.5x upper limit of normal (ULN)

Must not have

Unwilling or unable to stop GnRH antagonists, aromatase inhibitors, or anti-androgens

Unwilling or unable to stop supplemental sex hormone therapy (estrogen, progesterone, and/or testosterone preparations)

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year post treatment

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a mix of anti-inflammatory drugs and immune response controllers for patients with severe immune reactions after a transplant. The treatment aims to reduce harmful immune attacks and inflammation.

Who is the study for?

This trial is for HCT recipients over 12 years old with high-risk aGVHD, or standard risk aGVHD plus certain biomarkers. Participants need functioning kidneys and hearts, and must consent to the study. Excluded are those with current severe infections, hormone-responsive cancers, thrombosis, or unwilling to stop hormone therapies or avoid pregnancy.

What is being tested?

The study tests the lowest effective dose of corticosteroids combined with ruxolitinib and uhCG/EGF for treating high-risk acute Graft-versus-Host Disease (aGVHD). It's a single-arm phase I/II trial aiming to find this dose without affecting response rates at day 28.

What are the potential side effects?

Potential side effects include immune system suppression leading to increased infection risk, blood sugar increases from steroids, hormonal changes due to hCG/EGF therapy, and possible liver function alterations from ruxolitinib.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I am over 12 and starting treatment for severe aGVHD within 7 days.

Select...

My kidney function, measured by creatinine, is within the normal range.

Select...

I have been newly diagnosed with high-risk acute graft-versus-host disease.

Select...

My heart's pumping ability is at least 35%.

Select...

I have aGVHD with high amphiregulin levels according to the UMN test.

Select...

I have aGVHD and my risk level is confirmed by a specific test.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I cannot or will not stop taking hormone therapy for cancer.

Select...

I cannot or will not stop taking supplemental sex hormones.

Select...

I do not have any untreated serious infections.

Select...

I have had cancer that responded to hormone therapy.

Select...

I am not willing to use birth control during and for 30 days after treatment.

Select...

My cancer is getting worse.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 year post treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 year post treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 year post treatment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Best response of treatment in adult and children

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

Secondary study objectives

Collect blood samples and rectosigmoid biopsies for future correlative studies

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

Determine 1-year overall survival

+4 more

Side effects data

From 2018 Phase 4 trial • 2037 Patients • NCT01950819

34%

Oedema peripheral

24%

Constipation

24%

Diarrhoea

24%

Hypertension

22%

Anaemia

22%

Urinary tract infection

19%

Hypophosphataemia

19%

Nausea

16%

Hyperkalaemia

15%

Hypokalaemia

14%

Hyperglycaemia

14%

Blood creatinine increased

13%

Diabetes mellitus

13%

Hyperlipidaemia

13%

Headache

13%

Hypomagnesaemia

13%

Proteinuria

12%

Vomiting

11%

Nasopharyngitis

11%

Hypocalcaemia

11%

Pyrexia

10%

Tremor

10%

Dyslipidaemia

10%

Hypercholesterolaemia

10%

Haematuria

10%

Insomnia

Leukopenia

Back pain

Procedural pain

Abdominal pain

Metabolic acidosis

Cough

Upper respiratory tract infection

Thrombocytopenia

Dyspnoea

Pain in extremity

BK virus infection

Complications of transplanted kidney

Hypertriglyceridaemia

Acne

Arthralgia

Dysuria

Fatigue

Hypotension

Vitamin D deficiency

Pneumonia

Acute kidney injury

Polycythaemia

Tachycardia

Hyperuricaemia

Incision site pain

Dizziness

Anxiety

Transplant rejection

Abdominal pain upper

Weight increased

Hypercalcaemia

Alopecia

Lymphocele

Kidney transplant rejection

Gastroenteritis

Pyelonephritis

Sepsis

Pulmonary embolism

Cytomegalovirus infection

Renal impairment

Graft loss

Deep vein thrombosis

Leukocytosis

Urosepsis

Angina pectoris

Cardiac failure congestive

Impaired healing

Pneumocystis jirovecii pneumonia

Pyelonephritis acute

Septic shock

Delayed graft function

Incisional hernia

Transplant dysfunction

Dehydration

Osteonecrosis

Squamous cell carcinoma

Hydronephrosis

Urinary incontinence

Influenza

Basal cell carcinoma

Thrombotic microangiopathy

Wound dehiscence

Acute myocardial infarction

Atrial fibrillation

Cardiac failure

100%

80%

60%

40%

20%

Study treatment Arm

Everolimus Plus@Reduced CNI

MPA Plus Standard@CNI

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Ruxolitinib;hCG (Pregnyl®) ;CorticosteroidsExperimental Treatment3 Interventions

* 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

First Studied

Drug Approval Stage

How many patients have taken this drug

hCG

2013

Completed Phase 4

~4100

Corticosteroids

2003

Completed Phase 4

~8270

0 / 12Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Graft-versus-Host Disease (GVHD) include corticosteroids, ruxolitinib, and uhCG/EGF. Corticosteroids act as anti-inflammatory agents, reducing immune system activity and thereby decreasing inflammation and tissue damage. Ruxolitinib, a JAK1/2 inhibitor, disrupts immune signaling pathways, reducing T-cell proliferation and activity. uhCG/EGF, a novel combination, offers regenerative and anti-inflammatory benefits, aiding in tissue repair and reducing inflammation. These mechanisms are vital for GVHD patients as they help manage symptoms and improve treatment outcomes.