Status:
UNKNOWN
Immunotherapy Based on Antigen-specific Immune Effector Cells Targeting Neurofibromatosis or Schwannomatosis
Lead Sponsor:
Shenzhen Geno-Immune Medical Institute
Collaborating Sponsors:
Shenzhen Hospital of Southern Medical University
Shenzhen Children's Hospital
Conditions:
Cancer
Eligibility:
All Genders
1-80 years
Phase:
PHASE1
PHASE2
Brief Summary
The primary objective of this study is to verify the safety of antigen-specific T cells (CAR-T) and engineered immune effector cytotoxic T cells (EIE) modified by immunoregulatory genes and immune mod...
Detailed Description
Neurofibromatosis (NF) is caused by a genetic change that tends to develop benign tumors around nerves. NF is a lifelong condition that affects all populations equally, regardless of gender or ethnici...
Eligibility Criteria
Inclusion
- Written, informed consent obtained prior to any study-specific procedures.
- Diagnosis of neurofibromatosis, or schwannomatosis
- The results of immune staining of the patient's cancer specimens positive for any one or more of a list of tumor-associated antigens.
- Age ≥ 1 years
- At least one volumetrically measurable and ≥ 0.5 cc NF-related tumor (schwannoma, ependymoma, meningioma - histological confirmation not required) with radiographic evidence of progression (either as unequivocal progression on conventional MRI, or a \>10% volume increase by 3D volumetrics) over the past ≤12 months, designated as the primary target tumor OR Volumetrically measurable and ≥ 0.5 cc VS with ipsilateral progressive hearing loss over the past ≤12 months, designated as the primary target tumor.
- Progressive Hearing Loss Criteria for Enrollment: Audiogram showing drop in pure tone average (PTA) of 10dB HL at ≥ 2 nonconsecutive or consecutive frequencies or drop in speech discrimination score (SDS) below the 95% critical difference threshold, compared to previous audiogram ≤ 1 year prior.
- Karnofsky/Lansky performance status (PS) 50-100%. Note: Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
- Any neurologic deficits must be stable for ≥ 1 week.
- Adequate bone marrow reserve with
- absolute neutrophil count (ANC) ≥ 1000/mm3.
- Platelets ≥100,000/mm3.
- Adequate renal and hepatic function with
- Serum creatinine ≤ 2 x upper limit of normal (ULN).
- Serum bilirubin ≤ 2 x ULN.
- aspartate aminotransferase (AST)/ALT ≤ 2 x ULN.
- Alkaline phosphatase ≤ 5 x ULN.
- Serum bilirubin 2.0 is acceptable in the setting of known Gilbert's syndrome.
Exclusion
- The results of immune staining of the patient's tumor-associated antigens are all negative.
- Participation in any other cell therapy protocols within one year.
- Current or recent treatment (within the 28-day period prior to Day 0) with another investigational drug.
- Patients who have had a major surgery or significant traumatic injury within 4 weeks of start of study.
- Pregnant or lactating females.
- Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases.
- Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as:
- Symptomatic congestive heart failure of New York heart Association Class III or IV
- unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease
- severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or 02 saturation that is 88% or less at rest on room air
- uncontrolled diabetes as defined by fasting serum glucose \>1.5 x ULN (Note: Optimal glycemic control should be achieved before starting trial therapy.)
- active (acute or chronic) or uncontrolled severe infections
- liver disease such as cirrhosis or severe hepatic impairment (Child-Pugh class C).
- Inadequate bone marrow function:
- Absolute neutrophil count \< 1.0 x 10e9/L.• Platelet count \< 100 x 10e9/L.
- Hb \< 9 g/dL.
- Inadequate liver and renal function:
- Serum (total) bilirubin \> 1.5 x ULN.
- AST \& ALT \> 2.5 x ULN (\> 5 x ULN in patients with liver metastases).
- Alkaline phosphatase \> 2.5 x ULN (or \> 5 x ULN in case of liver metastases or \> 10 x ULN in case of bone metastases).
- Serum creatinine \>2.0 mg/dl (\> 177 μmol/L).
- Urine dipstick for protein uria should be \< 2+. Patients with ≥ 2+ proteinuria on dipstick urinalysis at baseline should undergo 24 hour urine collection and must demonstrate \< 1 g of protein/24 hr.
- Subject infected with HIV (HIV antibody positive), Treponema pallidum antibody positive or TB culture positive.
Key Trial Info
Start Date :
September 1 2019
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 31 2022
Estimated Enrollment :
100 Patients enrolled
Trial Details
Trial ID
NCT04085159
Start Date
September 1 2019
End Date
December 31 2022
Last Update
June 12 2020
Active Locations (3)
Enter a location and click search to find clinical trials sorted by distance.
1
Shenzhen Geno-immune Medical Institute
Shenzhen, Guangdong, China, 518000
2
Shenzhen Children's Hospital
Shenzhen, Guangdong, China, 518038
3
Department of Neurosurgery, Shenzhen Hospital, Southern Medical University
Shenzhen, Guangdong, China, 518100