Immunotherapy of the Paraneoplastic Syndromes

NCT ID: NCT00378326

Last Updated: 2023-09-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-04-30
• Study Completion Date: 2014-05-31

Brief Summary

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. 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.

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 (RU) (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. 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 New York, 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 New York, 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. 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.

Conditions

Paraneoplastic Syndromes

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Tacrolimus

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Other Intervention Names

FK506

Eligibility 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.

• Minimum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Rockefeller University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Darnell, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Rockefeller University

Locations

Rockefeller University Hospital

New York, New York, United States

Countries

United States

References

Orange D, Frank M, Tian S, Dousmanis A, Marmur R, Buckley N, Parveen S, Graber JJ, Blachere N, Darnell RB. Cellular immune suppression in paraneoplastic neurologic syndromes targeting intracellular antigens. Arch Neurol. 2012 Sep;69(9):1132-40. doi: 10.1001/archneurol.2012.595.

Reference Type: DERIVED

PMID: 22566506 (View on PubMed)

Other Identifiers

RDA-0572

Identifier Type: -

Identifier Source: org_study_id