Campath in Chronic GVHD

NCT00495755 | Completed Phase 1 Results

• 1 other identifier: DFCI 07-057
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

The CD52 antigen, which is targeted by alemtuzumab, is highly expressed on mature T lymphocytes, monocytes and monocyte-derived dendritic cells as well as on mature B cells. Due to its more promiscuous effect on immune cells, alemtuzumab not only targets antibody producing B lymphocytes as does rituximab, but also targets alloreactive T lymphocytes and dendritic cells that also contribute to the complex pathogenesis of chronic GVHD. Our hypothesis is that alemtuzumab will be effective in the treatment of chronic GVHD through its promiscuous depletion of alloreactive T lymphocytes, dendritic cells as well as antibody producing mature B-lymphocytes.

Conditions

Chronic Graft-vs.-Host Disease

Keywords

Chronic Graft-vs-Host Disease

Outcome Measures

Primary Outcomes (1)

• The Maximum Tolerated Dose (MTD) of a Four-week Course of Alemtuxumab in Chronic GVHD for Patients With an Incomplete Response to Steroids

  MTD: The dose at which fewer or equal to 2/6 experience a dose-limiting toxicity

  12 weeks

Secondary Outcomes (2)

• The Efficacy of a Four-week Course of Alemtuzumab in Patients With Steroid-refractory Chronic GVHD (cGVHD).

  12 weeks

• The Effect of Alemtuzumab Therapy on Parameters of Cellular and Humoral Immunity in the Late Post Transplant Period. This Information is Exploratory in Nature Only Due to the Heterogeneity of the Anticipated Patient Population.

  12

Study Arms (1)

Campath (alemtuzumab)

EXPERIMENTAL

Drug: Alemtuzumab (Campath)

Interventions

Alemtuzumab (Campath) DRUG

An escalating dose given over 4 weeks

Campath (alemtuzumab)

Eligibility Criteria

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

You may qualify if:

• Recipients of allogeneic stem cell transplantation using myeloablative or non-myeloablative conditioning regimens.
• Patients must be at least 180 days (6 months) from the allogeneic stem cell transplantation procedure.
• Patients must have steroid refractory chronic GVHD, defined as having persistent signs and symptoms of chronic GVHD despite the use of prednisone at \< 0.5 mg/kg/day or 1 mg/kg every other day for at least 4 weeks in the preceding 12 months (or equivalent dosing of alternate corticosteroids) without complete resolution of signs and symptoms. Patients with either extensive chronic GVHD or limited chronic GVHD requiring systemic therapy are eligible.
• Stable dose of corticosteroids for 4 weeks prior to enrollment.
• Less than 2mg/kg/day prednisone use (or equivalent).
• No addition or subtraction of other immunosuppressive medications (e.g. calcineurin inhibitors, sirolimus, mycophenolate mofetil) for 4 weeks prior to enrollment. The dose of immunosuppressive medicines may be adjusted based on the therapeutic range of that drug.
• Adequate bone marrow function indicated by:
• ANC\>1000/mm3
• Platelets\>50,000/mm3
• Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for six months after completion of treatment

You may not qualify if:

• Prednisone requirement\>2mg/kg/day or equivalent
• Known life-threatening hypersensitivity to alemtuzumab, other anti-B cell or anti-T cell antibodies.
• Prior exposure to any new immunosuppressive medication (or Extra Corporeal Phototherapy) in the preceding 4 weeks prior to enrollment.
• Active, uncontrolled infection.
• History of Hepatitis B or C infection.
• Active malignant disease relapse.
• Donor lymphocyte infusion within the preceding 100 days or plan for donor lymphocyte infusion in the coming 3 months.
• Life expectancy \<3 months.
• Pregnancy or lactation.
• Evidence of HIV seropositivity.
• Inability to comply with alemtuzumab treatment regimen.

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Genzyme, a Sanofi Company: collaborator
• Bayer: collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Interventions

Alemtuzumab

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Corey S. Cutler, MD, MPH, FRCP(C)
• Organization: Dana-Farber Cancer Institute

cscutler@partners.org

617-632-5946

Study Officials

• Corey Cutler, MD MPH FRCPC

  Dana-Farber Cancer Institute

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 2, 2007
• First Posted: July 3, 2007
• Study Start: July 1, 2007
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2012
• Last Updated: August 9, 2013
• Results First Posted: August 9, 2013

Record last verified: 2013-08

Locations

US (1)