What is the mechanism of action of this treatment?

PTCy (post-transplant cyclophosphamide) works by eliminating alloreactive T cells that cause GvHD, thereby reducing the immune response against the host. Bortezomib inhibits antigen-presenting cells and promotes the activity of regulatory T cells, which helps in controlling the immune response and maintaining tolerance. Abatacept blocks T-cell activation by interfering with the co-stimulatory signals required for T-cell activation, thus preventing the initiation of the immune response that leads to GvHD. These mechanisms are important for GvHD patients as they help in reducing the severity of the disease while allowing the transplanted cells to engraft and function properly.

What side effects are associated with this type of intervention?

The most common treatments for Graft-versus-Host Disease (GvHD) include PTCy, Bortezomib, and Abatacept. PTCy can cause side effects such as nausea, vomiting, diarrhea, liver enzyme elevation, and bone marrow suppression. Bortezomib is associated with peripheral neuropathy, gastrointestinal symptoms, and an increased risk of infections. Abatacept may lead to headaches, upper respiratory tract infections, and infusion-related reactions. These treatments aim to modulate the immune response but come with a range of potential adverse effects that need to be managed carefully.

What prior FDA approvals exist?

FDA-approved treatments for Graft-versus-Host Disease (GvHD) include cyclophosphamide (PTCy), which is used to eliminate alloreactive T cells, and bortezomib, which inhibits antigen-presenting cells and promotes regulatory T cells. Abatacept, which blocks T-cell activation, is also being studied for its potential in GvHD treatment. These drugs aim to modulate the immune response to prevent or treat GvHD by targeting different aspects of T-cell function and antigen presentation.

What other types of research exist?

Promising novel alternatives for GvHD treatment in 2024 include Belatacept (a costimulation blocker), ASKP1240 (blocks CD40/CD154 pathway), and CFZ533 (an anti-CD40 antibody). These agents are being explored for their potential to modulate immune responses and reduce the risk of GvHD.

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Alkylating agents

Cyclophosphamide + Bortezomib + Abatacept for Graft-versus-Host Disease

Phase 1 & 2

Recruiting

Led By Maher Abdul Hay, MD

Research Sponsored by NYU Langone Health

Eligibility Criteria Checklist

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

Must have

No evidence of progressive bacterial, viral, or fungal infection

Age ≥18 years

Must not have

Patient had myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see Appendix D), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at screening must be documented by the investigator as not medically relevant.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up day +1 to day +730

Awards & highlights

Approved for 20 Other Conditions

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

This trial is testing three new treatments to prevent a complication called GvHD in adults with blood cancers receiving stem cell transplants. It targets patients at high risk of GvHD due to their transplant type. The treatments work by calming the immune system to prevent it from attacking the body.

Who is the study for?

Adults with blood cancers eligible for a stem cell transplant from a matched donor can join. They must have good organ function, no severe infections, and be willing to follow the study plan. Pregnant women, those with recent heart issues or another cancer within 3 years (with some exceptions), or who cannot consent are excluded.

What is being tested?

The trial tests high-dose Cyclophosphamide, Bortezomib, and Abatacept as preventatives for Graft-versus-Host Disease after allogeneic HSCT in adults. It's a phase I-II study assessing the safety and effectiveness of these drugs post-transplant.

What are the potential side effects?

Possible side effects include immune system suppression leading to increased infection risk, potential damage to organs like the liver and kidneys, allergic reactions to medication components, gastrointestinal issues, and fatigue.

Eligibility Criteria

Inclusion Criteria

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

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I do not have any worsening infections.

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I am 18 years old or older.

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I am able to care for myself but may not be able to do active work.

Exclusion Criteria

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

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I haven't had a heart attack or severe heart issues in the last 6 months.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ day +1 to day +730

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~day +1 to day +730

This trial's timeline: 3 weeks for screening, Varies for treatment, and day +1 to day +730 for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Phase I:Incidence Dose limiting toxicity (DLT)

Phase II: Grades II-IV Acute GvHD

Secondary study objectives

Chronic GvHD

GvHD and relapse-free survival (GRFS)

Overall survival (OS)

+5 more

Side effects data

From 2022 Phase 3 trial • 402 Patients • NCT03110562

50%

Thrombocytopenia

45%

Anaemia

39%

Nausea

29%

Decreased appetite

29%

Diarrhoea

27%

Weight decreased

24%

Neuropathy peripheral

24%

Vomiting

23%

Fatigue

21%

Neutropenia

21%

Cataract

15%

Asthenia

12%

Upper respiratory tract infection

11%

Constipation

11%

Pyrexia

Oedema peripheral

Pneumonia

Dizziness

Insomnia

Dehydration

Back pain

Leukopenia

Bronchitis

Cough

Lymphopenia

Acute kidney injury

Abdominal pain

Muscular weakness

Lower respiratory tract infection

Sepsis

Hyperglycaemia

Urinary tract infection

Nasopharyngitis

Hyponatraemia

Pain in extremity

Toothache

Disturbance in attention

Cardiac failure

Hypertension

Embolism

Cardiac failure acute

Pulmonary contusion

Peripheral swelling

Blood creatinine increased

Paraesthesia

Infection

Respiratory syncytial virus infection

Dyspepsia

Syncope

Clostridium difficile infection

Compression fracture

Multiple fractures

Haemoglobin decreased

Myocardial infarction

C-reactive protein increased

Cerebral haemorrhage

Ischaemic stroke

Sudden death

Oropharyngeal pain

Cognitive disorder

Confusional state

Influenza

Septic shock

Osteonecrosis of jaw

Taste disorder

Hyperkalaemia

Blood uric acid increased

Depression

Cerebrovascular accident

Bronchitis viral

100%

80%

60%

40%

20%

Study treatment Arm

SVdX Arm: Selinexor + Bortezomib + Dexamethasone

SdX Arm: Selinexor + Dexamethasone

SVd Arm: Selinexor + Bortezomib + Dexamethasone

Vd Arm: Bortezomib + Dexamethasone

Awards & Highlights

Approved for 20 Other Conditions

This treatment demonstrated efficacy for 20 other conditions.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

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: Participants with hematological malignanciesExperimental Treatment3 Interventions

Participants undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) will receive a combination of cyclophosphamide, known commercially as Cytoxan®, abatacept, known as Orecia® and bortezomib commercially known as Velcade®, to reduce the rate of graft-versus-host disease (GvHD). These medications will be given for GvHD prevention during the transplant process.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cyclophosphamide

FDA approved

Abatacept

FDA approved

Bortezomib

FDA approved

0 / 4Eligibility 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

PTCy (post-transplant cyclophosphamide) works by eliminating alloreactive T cells that cause GvHD, thereby reducing the immune response against the host. Bortezomib inhibits antigen-presenting cells and promotes the activity of regulatory T cells, which helps in controlling the immune response and maintaining tolerance. Abatacept blocks T-cell activation by interfering with the co-stimulatory signals required for T-cell activation, thus preventing the initiation of the immune response that leads to GvHD. These mechanisms are important for GvHD patients as they help in reducing the severity of the disease while allowing the transplanted cells to engraft and function properly.