Immunotherapy of the Paraneoplastic Syndromes

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Rockefeller University
Sponsor:
Information provided by (Responsible Party):
Rockefeller University
ClinicalTrials.gov Identifier:
NCT00378326
First received: September 18, 2006
Last updated: May 5, 2014
Last verified: May 2014
  Purpose

We treat a subset of patients with paraneoplastic neurologic disorders, including those with Yo-mediated paraneoplastic cerebellar degeneration (PCD), the Hu syndrome, which is most commonly associated with small cell lung cancer (SCLC) - paraneoplastic subacute sensory neuropathy, encephalomyelitis, limbic encephalopathy, autonomic neuropathy - and the Ri Syndrome (a.k.a. POMA - Paraneoplastic Opsoclonus-Myoclonus Ataxia), as well as those patients suspected to have a paraneoplastic neurologic disorder but in whom a characteristic antibody has not yet been identified. Our treatment protocol consists of immune suppression therapy using tacrolimus (FK506), a potent inhibitor of lymphocyte proliferation that is commonly used to prevent organ transplant rejection.


Condition Intervention
Paraneoplastic Syndromes
Drug: Tacrolimus (FK506)

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Immunotherapy of the Paraneoplastic Syndromes

Resource links provided by NLM:


Further study details as provided by Rockefeller University:

Primary Outcome Measures:
  • Assessment of immune responses [ Time Frame: throughout study ] [ Designated as safety issue: No ]
  • Clinical response in PND patients who are treated with Tacrolimus and Prednisone [ Time Frame: throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Collection and archiving of serum and lymphocytes for future studies on the mechanism of neuronal autoimmunity. [ Time Frame: end of study ] [ Designated as safety issue: No ]

Estimated Enrollment: 100
Study Start Date: April 2006
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tacrolimus
Tacrolimus at doses of 0.15- 0.3mg/kg/day in two divided oral doses, in conjunction with, initially, up to 60mg/day of oral prednisone
Drug: Tacrolimus (FK506)
Tacrolimus at doses of 0.15- 0.3mg/kg/day in two divided oral doses, in conjunction with, initially, up to 60mg/day of oral prednisone

Detailed Description:

patients may stay either in-hospital while being treated with Tacrolimus, receive treatment as an outpatient, or a combination of the two. Additionally, patients who are too sick to be treated at Rockefeller University (eg. patients actively seizing), but are in need of urgent treatment, may be treated at either Memorial Sloan-Kettering Cancer Center or New York-Presbyterian Hospital in conjunction with MDs there. Dr. Robert Darnell, being credentialed at both institutions, will be the primary person responsible for monitoring all portions of the study performed at MSKCC and New York-Presbyterian Hospital. During treatment, patients will undergo blood draws, at set intervals (see section g below), clinical evaluation, possibly repeat leukapheresis or large volume blood draw, and lumbar puncture (see below). Since many patients live far away from NY, some of these procedures may be performed by RU staff or in conjunction with their local MDs.

Patients who are terminated from Tacrolimus treatment after 7-21 days will be followed up as outpatients for evaluation of their neurologic and medical status. Wherever possible, these patients will be seen on days 3 and 10 post treatment termination, and then on a biweekly basis for two months. Since many patients live far away from NY, they may instead be monitored in conjunction with their local MDs. Patients who show a definite clinical response to Tacrolimus may be maintained on a therapeutic dose for up to one year, and will be followed as outpatients. For patients receiving retreatment, they may be treated as inpatients or on an outpatient basis, at the discretion of the PI, on the same schedule as patients being treated initially (see 10.g.). Long term improvement or decline in neurologic function will be objectively assessed by neurologic exam, which will be quantified by use of the Karnofsky scale (a measure of functional neurologic status). Since the vast majority of Hu patients decline over a 6-12 month period following diagnosis, a stable or improved Karnofsky score over such a time period will be taken as a measure of successful treatment. Repeat lumbar puncture (up to eight per year) and leukapheresis or large volume blood draw (approx. 100 cc) may be performed (up to four of each per year), especially in the setting of neurologic change, to assess the immune responses to the medications.

  Eligibility

Ages Eligible for Study:   16 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients diagnosed with Paraneoplastic Disorder

Exclusion Criteria:

  • Metastasis (spread) of cancer to brain, History of additional active malignancy other than non-melanoma skin cancer, History of Hepatitis B, Hepatitis C, HIV or Syphilis.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00378326

Contacts
Contact: Mayu Frank, NP 212-327-7443 frankm@rockefeller.edu

Locations
United States, New York
Rockefeller University Hospital Recruiting
New York, New York, United States, 10021
Principal Investigator: Robert Darnell, MD, PhD         
Sponsors and Collaborators
Rockefeller University
Investigators
Principal Investigator: Robert Darnell, MD, PhD Rockefeller University
  More Information

No publications provided by Rockefeller University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Rockefeller University
ClinicalTrials.gov Identifier: NCT00378326     History of Changes
Other Study ID Numbers: RDA-0572
Study First Received: September 18, 2006
Last Updated: May 5, 2014
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Rockefeller University:
paraneoplastic syndrome

Additional relevant MeSH terms:
Paraneoplastic Syndromes
Neoplasms
Tacrolimus
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 01, 2014