NCT02133924

Brief Summary

This research trial is designed to study the safety and effectiveness of combining the study drug, Natalizumab (Tysabri®) with the standard treatment, the use of steroids, as a new treatment for acute graft versus host disease (acute GVHD). GVHD is the most common serious complication, after bone marrow transplant. GVHD occurs when the donor cells (the graft), treat the recipient's body as "foreign" and attack the cells in the recipient's body. During this immune system response, donor cells damage body tissues, such as the skin, liver, stomach, and/or intestines. Acute GVHD can be severe and if severe, potentially fatal to the transplant recipient. Acute GVHD usually happens within the first several months after transplant. The goal of this research is to develop a safer and more effective treatment for acute GVHD, and particularly for acute GVHD that affects the gastrointestinal (or GI) tract, with the ultimate goal being safer and more effective transplant therapies for blood cancers such as leukemia, lymphoma, and multiple myeloma.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
76

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Aug 2016

Longer than P75 for phase_2

Geographic Reach
1 country

12 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 6, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

May 8, 2014

Completed
2.2 years until next milestone

Study Start

First participant enrolled

August 1, 2016

Completed
4.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 10, 2020

Completed
12 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 21, 2021

Completed
11 months until next milestone

Results Posted

Study results publicly available

October 21, 2022

Completed
Last Updated

October 21, 2022

Status Verified

October 1, 2022

Enrollment Period

4.4 years

First QC Date

May 6, 2014

Results QC Date

August 25, 2022

Last Update Submit

October 20, 2022

Conditions

Acute Graft Versus Host Disease

Keywords

Graft vs Host DiseaseGraft vs Host Reactionallogeneic bone marrow transplantationallogeneic hematopoietic stem cell transplantationadverse effects

Outcome Measures

Primary Outcomes (1)

  • Number of Participants With Complete Response (CR)

    The primary endpoint for this clinical study is the proportion of complete response, CR (that is, the percent of patients with skin, liver, and GI GVHD - all stage 0) at day 28 of study treatment. Stage 0 = no rash, total bilirubin \<2 mg/dl, diarrhea \<500 ml/d

    Day 28

Secondary Outcomes (7)

  • Number of Participants With Overall Survival (OS)

    1 year

  • Number of Participants With Non-Relapse Mortality (NRM)

    6 months and 1 year

  • Number of Participants With SR GVHD

    1 year

  • Time to Discontinuation of Steroid Therapy

    up to 365 days

  • Number of Participants Who Received Additional GVHD Therapies

    1 year

  • +2 more secondary outcomes

Study Arms (1)

Natalizumab with steroids

EXPERIMENTAL

For subjects whose GVHD assay is Ann Arbor score 2 or 3, the study treatment will consist of two drugs, prednisone (or methylprednisolone) and natalizumab. Protocol treatment must start within 3 days of the subject's diagnosis of acute GVHD.

Drug: natalizumabDrug: steroids

Interventions

natalizumabDRUG

Natalizumab 300mg on days 0 and 14.

Also known as: Tysabri
Natalizumab with steroids
steroidsDRUG

Prednisone 2mg/kg/d (or methyl-prednisolone IV equivalent)

Also known as: Prednisone, methylprednisolone equivalent IV
Natalizumab with steroids

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • New onset high risk acute GVHD (Ann Arbor score 2 or3 as defined in Appendix C of the protocol) following allogeneic bone marrow transplantation. Any clinical severity (Glucksberg grade I-IV) is eligible. Patients with prior or existing diagnosis of GVHD without any treatment are eligible. Patients given only topical corticosteroids for skin GVHD are eligible.
  • Any donor type (e.g., related, unrelated) or stem cell source (bone marrow, peripheral blood, cord blood). Recipients of non-myeloablative and myeloablative transplants are eligible.
  • No prior systemic treatment for acute GVHD except for a maximum of 3 days of prednisone ≤2 mg/kg/day (or IV methylprednisolone). Topical skin steroid treatment, non-absorbable oral steroid treatment for GI GVHD, and resumption of GVHD prophylaxis agents (e.g., calcineurin inhibitors) are permissible. Patients enrolled in BMT CTN 1501 who randomized to sirolimus are also eligible.
  • Age 18 years or older.
  • Direct bilirubin must be \<2 mg/dL unless the elevation is known to be due to Gilbert syndrome or aGVHD within 3 days of enrollment.
  • ALT/SGPT and AST/SGOT must be \<5 x the upper limit of the normal range within 3 days of enrollment, unless the elevation is due to liver GVHD.
  • If the patient is a woman of child-bearing potential, the patient and their sexual partner must agree to practice effective contraception.
  • Written informed consent from patient.
  • Biopsy of acute GVHD target organ is strongly recommended, but not required. Enrollment should not be delayed for biopsy or pathology results. Patients who do not enroll within 3 days of systemic steroid treatment for acute GVHD are not permitted to participate.

You may not qualify if:

  • Progressive or relapsed malignancy since BMT
  • Uncontrolled active infection
  • Patients with chronic GVHD only. Patient with overlap syndrome are eligible.
  • History of Progressive Multifocal Leukoencephalopathy (PML)
  • Known hypersensitivity to natalizumab
  • Pregnant or nursing (lactating) women
  • Use of other drugs for the treatment of acute GVHD
  • Steroid therapy for indications other than GVHD at doses \>0.5 mg/kg/d of methylprednisolone or equivalent within 7 days prior to initiation of GVHD treatment
  • Patients on dialysis
  • Patients requiring ventilator support
  • Investigational agent within 30 days of enrollment without approval from the Sponsor-Investigator

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (12)

City of Hope

Duarte, California, 91010, United States

Location

Emory University

Atlanta, Georgia, 30008, United States

Location

Northwestern

Chicago, Illinois, 60611, United States

Location

The University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Mayo Clinical

Rochester, Minnesota, 55905, United States

Location

Mount Sinai Health System

New York, New York, 10029, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Pennsylvania, Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University

Nashville, Tennessee, 37232, United States

Location

Related Publications (1)

  • Al Malki MM, London K, Baez J, Akahoshi Y, Hogan WJ, Etra A, Choe H, Hexner E, Langston A, Abhyankar S, Ponce DM, DeFilipp Z, Kitko CL, Adekola K, Reshef R, Ayuk F, Capellini A, Chanswangphuwana C, Eder M, Eng G, Gandhi I, Grupp S, Gleich S, Holler E, Javorniczky NR, Kasikis S, Kowalyk S, Morales G, Ozbek U, Rosler W, Spyrou N, Yanik G, Young R, Chen YB, Nakamura R, Ferrara JLM, Levine JE. Phase 2 study of natalizumab plus standard corticosteroid treatment for high-risk acute graft-versus-host disease. Blood Adv. 2023 Sep 12;7(17):5189-5198. doi: 10.1182/bloodadvances.2023009853.

    PMID: 37235690DERIVED

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

NatalizumabSteroidsPrednisone

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsFused-Ring CompoundsPolycyclic CompoundsPregnadienediolsPregnadienesPregnanes

Results Point of Contact

Title
Dr. John Levine
Organization
Icahn School of Medicine at Mount Sinai
john.levine@mssm.edu
212-241-3429

Study Officials

  • John E Levine, MD

    Icahn School of Medicine at Mount Sinai

    STUDY CHAIR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Professor of Internal Medicine and Pediatrics, Director of BMT Clinical Research

Study Record Dates

First Submitted

May 6, 2014

First Posted

May 8, 2014

Study Start

August 1, 2016

Primary Completion

December 10, 2020

Study Completion

November 21, 2021

Last Updated

October 21, 2022

Results First Posted

October 21, 2022

Record last verified: 2022-10

Locations

US(12)