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Graft Versus Host DiseasePhase 2NCT02176031

Phase II Trial of Natalizumab + Prednisone for Initial Therapy of Acute GI GVHD

A Phase 2 study testing Natalizumab and Methylprednisolone in people with Graft Versus Host Disease, run by Dana-Farber Cancer Institute at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug Natalizumab in treating Acute Graft-Versus-Host Disease (GVHD) in the Gastrointestinal (GI) Tract. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Graft Versus Host Disease
What is being tested?
Natalizumab and Methylprednisolone
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
2 sitesUnited States
Study dates
Jan 2015to Feb 2019
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants must meet the following criteria on screening examination to be eligible to participate in the study:
  • Participants must have acute Graft-Versus-Host Disease (GVHD) of the lower gastrointestinal tract as defined by the clinical impression of the treating physician, requiring systemic treatment. Minimum criteria for GI GVHD includes diarrhea of greater than 500 mL/day. Biopsy of the GI tract is required for study entry and must confirm the diagnosis of acute GVHD. Stool samples to rule out infectious causes of diarrhea, including norovirus, Clostridium difficile and other clinically indicated infections must also be negative. Eligibility includes:
  • Acute GVHD developing after allogeneic hematopoietic stem cell transplantation (HSCT) using bone marrow, peripheral blood stem cells, or umbilical cord blood. Recipients of non-myeloablative, reduced intensity and myeloablative transplants are eligible.
  • Patients who develop acute GVHD after donor lymphocyte infusion (DLI) are eligible.
  • There is no specified time window after day 0 of transplant as acute GVHD is only defined by clinical manifestations.
  • Patients must have experienced neutrophil engraftment after HSCT as defined by absolute neutrophil counts ≥ 500 / µL × 3 consecutive measurements. Absolute neutrophil count (ANC) should be calculated using the standard formula (Neut + Bands)(WBC × 101).
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  • The presence of hepatic, upper GI and/or cutaneous acute GVHD is permitted.
  • Steroids can be started up to 7 days prior to the administration of natalizumab.
  • Age ≥ 18
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study:
  • Patients with the entity of Acute/Chronic GVHD overlap syndromes.
  • Requiring mechanical ventilation
  • Vasopressor requirement
  • Concurrent hepatic veno-occlusive disease (VOD) based on clinical examination
  • Karnofsky performance status < 30
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  • Participants may not be receiving any other study agents for at least 7 days prior to enrollment
  • Prior use of natalizumab for any reason is not allowed
  • Pregnant women are excluded from this study because of the potential teratogenic effects of natalizumab. Because natalizumab enters breast milk, and the effect is unknown in infants, breastfeeding should be discontinued if the mother is treated with natalizumab.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02115

Other trials in United States

About this study

Official title: Phase II Trial of Natalizumab (Tysabri®) Plus Prednisone for Initial Therapy of Acute Graft Versus Host Disease (aGVHD) of the Gastrointestinal Tract

This research study is a Phase II clinical trial, which tests the safety and effectiveness of an investigational drug Natalizumab in treating Acute Graft-Versus-Host Disease (GVHD) in the Gastrointestinal (GI) Tract.

Read the detailed description

Natalizumab is a drug that was initially discovered as a treatment for autoimmune conditions. Natalizumab has been approved for use in patients with Multiple Sclerosis and Crohn's disease. In these diseases, the drug works to inhibit dysfunctional immune cells that are responsible for the symptoms seen in these diseases. Acute graft versus host disease is caused by a similar dysfunction of immune cells; Natalizumab is thought to inhibit these immune cells, similarly to how it does in Multiple Sclerosis and Crohn's disease. In this research study,the investigators are looking to see whether Natalizumab provides additional benefit to patients receiving standard treatment for acute graft versus host disease of the gastrointestinal tract.

Participants who fulfill eligibility criteria will be entered into the trial to receive Natalizumab.

  • Participant will receive a dose of the natalizumab through intravenous infusion. Participants may receive a second dose at Day 28 if they experience a partial response or very good partial response.
  • Scheduled Physical Examination at screening, during the week of first dose and at 28 days, 56 days, 100 days, 180 days and one year.
Being tested
Natalizumab, Methylprednisolone
Keywords
Graft Versus Host Disease
Medical subject headings
Graft vs Host Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT02176031
Study groupRoleWhat they receive
NatalizumabExperimentalNatalizumab- * (Day 0 and 28) Fixed dose Intravenous infusion over one hour. 2 hours observation completion of the infusion * At 4 weeks, if there has been less than a complete response participants can be treated with a second dose of natalizumab. * If participants have no response after one dose, they will be not be given a second dose. * Participants who receive a second dose of natalizumab will be evaluated for response at day 56 after first treatment dose administered. * Participants will be assessed for response to therapy with natalizumab at day +28, day +56, day +100, day + 180, and day +365. * Commercial supplies of Methylprednisolone (or equivalent steroid) will be utilized. The formulation, preparation and route of administration will be as per package insert
Receives: Drug: Natalizumab; Drug: Methylprednisolone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. GVHD-free Survival Rate

    Graft-versus-host disease (GVHD) free survival is defined as achieving complete response without death or relapse or requiring secondary immunosuppressive therapy . Proportions are reported descriptively. GVHD-free survival was assessed using the Kaplan-Meier method.

    Measured: Day 56

Secondary outcomes (5)

  1. Graft-verus-host Disease (GVHD) Response Rate

    • Complete Response (CR) is defined as resolution of all signs and symptoms of acute GVHD.
    • Very Good Partial Response (VGPR) is defined by no rash or residual erythematous rash involving less than 25% of the body surface, and total serum bilirubin concentration less than 2 mg/dL or less than 25% of baseline at enrollment and tolerating food or enteral feeding, predominantly formed stools, no overt gastrointestinal bleeding or abdominal cramping, and no more than occasional nausea and vomiting.
    • Partial Response (PR) is defined as an improvement of one stage in one or more organs without progression in any other organ.
    • Non-response (NR) is defined as no reduction in any GVHD organ staging.
    • Progression is defined as either new organ involvement on day +8 or thereafter, or increased organ specific symptoms sufficient to increase the organ stage by one or more or the initiation of an additional GVHD agent.
    • Overall Response Rate (ORR) is the sum of CR, VGPR, and PR.

    Measured: 28 Days, 56 Days

  2. GI aGVHD Response Rate

    Gastrointestinal (GI) acute graft-versus-host disease (GVHD) Response is defined by complete response, very good partial response, or partial response in signs and symptoms of GI aGVHD.

    Measured: Day 28, Day 56

  3. Overall Survival (OS) Rate

    Overall survival (OS) is defined from the date of natalizumab infusion to death or censored at last clinical evaluation. OS was estimated using the Kaplan-Meier method.

    Measured: 2 years

  4. Rate of GVHD Flares

    Number of subjects who experienced graft-versus-host disease (GVHD) flares requiring therapy after initial complete response (CR) or partial response (PR) by day 28 after the first dose of Natalizumab.

    Measured: by Day 28

  5. Percentage Steroid Dose Was Reduced at Day 28, 56, and 100 in Comparison to Steroid Dose at First Administration of Natalizumab.

    Median percentage steroid dose was reduced at Day 28, Day 56, and Day 100 in comparison to steroid dose at first administration of Natalizumab.

    Measured: Day 28, 56, and 100

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted26 Jun 2014 (estimated)
  2. Study startJan 2015
  3. Primary completionFeb 2019
  4. Study completionFeb 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02176031
Sponsor's protocol ID
14-140
Status last verified
Apr 2020
First submitted
25 Jun 2014
Last updated
17 Apr 2020
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Natalizumab and Methylprednisolone in people with Graft Versus Host Disease, run by Dana-Farber Cancer Institute at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Apr 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

GVHD-free Survival Rate (time frame: Day 56). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02176031.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2020.

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