A Single Arm, Open-Label Study To Evaluate The Safety, Tolerability And Preliminary Efficacy Of NM-IL-12 (rHuIL-12) In Patients With Cutaneous T Cell Lymphoma (CTCL) Undergoing Low Dose Total Skin Electron Beam Therapy (TSEBT)
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Cutaneous T Cell Lymphoma (CTCL)
- Sponsor
- Neumedicines Inc.
- Enrollment
- 10
- Locations
- 3
- Primary Endpoint
- Safety and tolerability will be evaluated on the basis of the following parameters (Vital signs, physical examination,Toxicity according to the NCI CTCAE, Immunogenicity evaluated by the presence of anti-drug antibody) :
- Last Updated
- 7 years ago
Overview
Brief Summary
In the proposed study, NM-IL-12 will be evaluated as immunotherapy to increase antitumor efficacy against CTCL, while reducing skin-related toxicity, when combined with low-dose TSEBT therapy. Determination of the maximum tolerated dose (MTD) for NM-IL-12 is not planned in this study, rather, a pre-defined starting dose will be explored; this dose is based on two safety and tolerability studies of NM-IL-12 in healthy volunteers.
Detailed Description
This is a single arm, open-label, non-randomized study with NM-IL-12 dosed in combination with low dose TSEBT in CTCL patients. This study is planned to be conducted in 10 patients, 18 years or older in age, undergoing low dose TSEBT of 12 Gy over a 3-week period. The study will initially enroll 4 patients and then will be expanded to enroll 6 additional patients (total 10 patients) depending on the presence or absence of Dose Modifying Criteria (DMC). Decision whether to de-escalate will be made after first 4 patients are followed up for 28 days from the first dose of NM-IL-12. Safety monitoring will continue throughout the whole period of drug administration and the treatment will be discontinued if intolerable toxicity or disease progression occurs during this period.
Investigators
Eligibility Criteria
Inclusion Criteria
- •18 years of age or older
- •Biopsy-confirmed CD4+ mycosis fungoides or Sézary syndrome, stage IB to IIIB
- •The patient is eligible for TSEBT
- •Eastern Cooperative Oncology Group (ECOG) of ≤
- •Adequate bone marrow function: WBC \> 2000/μL; platelet count \> 75,000/μL; Neutrophil count \> 1000/μL, without use of colony stimulating factors (CSF).
- •Required washout period for prior therapies Topical therapy: 2 weeks
- •Phototherapy (PUVA): 4 weeks
- •Local Skin Radiation Therapy (\< 10% skin surface): 4 weeks
- •Retinoids: 4 weeks
- •Interferons: 4 weeks
Exclusion Criteria
- •Biopsy confirmed CD8+ CTCL histology
- •Large cell transformation
- •Prior systemic use of any immunosuppressive chemotherapy (except low dose methotrexate) and/or monoclonal antibody treatment for CTCL
- •Prior courses of TSEBT (Note: localized skin-directed radiotherapy is allowed if administered at least 4 weeks prior to initiation on study).
- •Concomitant use of any anti-cancer therapy or immune modifier.
- •Prior allogeneic hematopoietic cell transplant.
- •Any ongoing infection whether receiving or not receiving antibiotics or have received intravenous antibiotics, antiviral, or antifungal agents within 2 weeks prior to the start of the study drug.
- •Known history of human immunodeficiency virus (HIV), hepatitis B or C
- •For women on estrogen based contraceptives, family history of venous thromboembolism (VTE) and/or risk factors predisposing for VTE and other medical conditions known to be associated with VTE.
- •History of prior malignancy with the exception of cervical intraepithelial neoplasia, non-melanoma skin cancer, and adequately treated localized prostate carcinoma (PSA \<1.0). Patients with a history of other malignancies must have undergone potentially curative therapy and have no evidence of that disease for five years
Outcomes
Primary Outcomes
Safety and tolerability will be evaluated on the basis of the following parameters (Vital signs, physical examination,Toxicity according to the NCI CTCAE, Immunogenicity evaluated by the presence of anti-drug antibody) :
Time Frame: 107 weeks
General safety: Vital signs (temperature, blood pressure, pulse rate, respiratory rate) and physical examination. Toxicity according to the NCI CTCAE (v4.03) for AEs and clinical laboratory profile; AEs will be collected in all patients who received at least one dose of NM-IL-12 and up to four weeks post last NM-IL-12 dose. Immunogenicity of NM-IL-12 will be evaluated by the presence of anti-drug antibody (ADA)
Secondary Outcomes
- Clinical Response measured by a modified severity-weighted assessment tool (mSWAT)(107 weeks)
- Progression free survival(107 weeks)