Open-label, Dose escalation, followed by Double-blind, Randomized, Two-dose, Parallel Group, Multi-center Clinical Trial of HuMax-CD4, a Fully Human Monoclonal Anti-CD4 Antibody, in Patients with Mycosis Fungoides type CTCL (stage IB-IVB) who are Refractory or Intolerant to Targretin® (bexarotene) and one other Standard Therapy - HuMax-CD4 in Refractory Mycosis Fungoides
- Conditions
- Refractory Mycosis Fungoides type CTCL (stage IB-IVB).The study population will be patients who are refractory to or intolerant to at least two prior therapies, one being Targretin, the other being the current standard of care at each institution.MedDRA version: 8.1Level: LLTClassification code 10028502Term: Mycosis fungoides refractory
- Registration Number
- EUCTR2006-003353-24-FR
- Lead Sponsor
- Genmab A/S
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 92
1) A biopsy compatible with the diagnosis of MF with a CD4 positive phenotype within 6 months of study entry
2) MF stage IB to IVB (highest stage ever)
3) Refractory to or intolerant to at least two prior therapies, one being Targretin® (or combinations hereof), and the other being the current standard therapy at each institution. Stage 1 patients are only required to be refractory or intolerant to at least one prior current standard therapy
• Refractory is defined as:
- resistance to therapy due to lack of response (defined as failure to obtain at least a 50% reduction in the disease for at least 6 months)
- progression of disease (defined as worsening of the disease by 25% or more compared to pre-treatment status) during therapy or within three months after cessation of therapy
• Intolerance to prior therapy is defined as:
- Discontinuation of therapy due to side effects/toxicity of the therapy, whether or not response occurred. Side effects/toxicity of Targretin therapy which qualify for the intolerance criteria are isolated hypertriglyceridemia or combined hypertriglyceridemia/hypercholesterolemia despite dose reduction of Targretin and concomitant administration of anti-lipemic therapy, defined as:
a) Isolated hypertriglyceridemia defined as Triglycerides > 400 mg/d
b) Combined hypertriglyceridemia/hypercholesterolemia for non-diabetic patients Triglycerides > 200 mg/dL plus LDL cholesterol > 160 mg/dL or Triglycerides > 200 mg/dL plus HDL cholesterol < 40 mg/dL
c) Combined hypertriglyceridemia/hypercholesterolemia in diabetic patients (type I and II): Triglycerides > 150 mg/dL plus LDL cholesterol > 130 mg/dL or Triglycerides > 150 mg/dL plus HDL cholesterol < 40 mg/dL
- Other side effects/toxicities of Targretin, despite dose reduction, which qualify for the intolerance criteria:
d) ALT > 3 times upper limit of normal
e) AST > 3 times upper limit of normal
f) Bilirubin > 3 times upper limit of normal
g) NCI grade 3 leucopenia
h) Uncorrectable hypothyroidism
i) Drug related dermatitis
• Ineligibility (as part of the intolerance criteria) to treatment with Targretin® despite administration of anti-lipemic therapy or due to concurrent medical conditions, such as:
- Isolated hypertriglyceridemia or combined hypertriglyceridemia/
hypercholesterolemia, defined as:
a) Isolated hypertriglyceridemia defined as Triglycerides > 400 mg/dL
b) Combined hypertriglyceridemia/hypercholesterolemia in non-diabetic patients defined as Triglycerides > 200 mg/dL plus LDL cholesterol > 160 mg/dL or Triglycerides > 200 mg/dL plus HDL cholesterol < 40 mg/dL
c) Combined hypertriglyceridemia/hypercholesterolemia in diabetic patients (Type I and II): Triglycerides > 150 mg/dL plus LDL cholesterol > 130 mg/dL or Triglycerides > 150 mg/dL plus HDL cholesterol < 40 mg/dL
- Prior pancreatitis
- Recurrent biliary colic
- Known hypersensitivity to retinoids
- Incapability to swallow Targretin capsules
4. WHO performance status 0, 1 or 2
5. Age = 18 years
6. Following receipt of verbal and written information about the study, the patient must provide signed consent before any study related activity is carried out
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range
1. Sezary syndrome
2. Primary cutaneous anaplastic large cell lymphoma
3. Lymphomatoid papulosis
4. Histopathological evidence of sheets of large cells (from skin or nodes) or poorly differentiated tumors
5. Prior treatment with combination chemotherapy within six months
6. Prior treatment with Total Skin Electron Beam (TSEB) therapy within one year
7. Prior treatment with Campath (alemtuzumab)
8. Prior treatment with more than three regimens of single agent chemotherapy
9. Prior treatment with pentostatin within two years
10. Treatment within 4 weeks prior to visit 2 with topical Targretin®, skin directed therapies or systemic anticancer therapies, such as, but not limited to: Targretin® , UV-light therapy, local Electron Beam Therapy (EBT), extracorporal photo chemotherapy, methotrexate, bleomycin, cyclophosphamide, oral retinoids, systemic glucocorticosteroids, carmustine, nitrogen mustard, systemic vitamin A or etretinate
11. Treatment with topical glucocorticosteroids within 2 weeks prior to visit 2
12. Unwillingness or inability to avoid prolonged exposure to the sun or UV light sufficient to produce a mild erythema or thought by the investigator to likely modify the patient’s disease
13. Concurrent or previous malignancies within the past five years except adequately treated in situ carcinoma of the uterine cervix or basal or squamous cell skin carcinoma
14. Acute or chronic infectious disease (including herpes simplex and herpes zoster) requiring medication except patients taking dicloxillin for carriage of staphylococcus
15. Significant concurrent, uncontrolled, or active medical condition including, but not limited to renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, cerebral or psychiatric disease
16. Screening blood laboratory values:
a) Hemoglobin < 8.5 g/dL
b) WBC = 2.5 x 10^9 cells/L
c) Platelets < 100 x 10^9 cells/L
d) ALT/AST > 2.5 times upper limit of normal
e) S-Creatinine > 1.5 mg/dL
f) CD3+ CD4+ cell count > 2000 cells/mm^3
g) CD4/CD8 ratio of 10 or higher
h) CD4+ CD7– cells = 40% of CD4+ cells
i) CD4+ CD26– cells = 40% of CD4+ cells
17. Known or suspected positive serology for HIV
18. Known or suspected positive serology for hepatitis B or C
19. Signs or symptoms of CNS involvement
20. Patients who are currently participating in any other trials or having received treatment with any experimental agent within 4 weeks prior to visit 1 (screening)
21. Prior treatment with anti-CD4 monoclonal antibodies
22. Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder)
23. Breast feeding women or women with a positive pregnancy test at Visit 1
24. Women of childbearing potential not willing to use either hormonal birth control, an intrauterine device or double-barrier method for the entire study period
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Primary end point(s): Objective response rate defined as proportion of patients achieving CR, CCR and PR as assessed by Physician’s Global Assessment of Clinical Condition (PGA) during treatment and 8 weeks of follow-up ;Main Objective: The primary objective is to determine the efficacy of HuMax-CD4 in patients with MF who are refractory or intolerant to treatment with Targretin® and one other standard therapy.;Secondary Objective: Secondary objectives are to explore safety and relief of symptoms and characterize the pharmacokinetic profile of HuMax-CD4 in patients with MF who are refractory or intolerant to treatment with Targretin® and one other standard therapy.
- Secondary Outcome Measures
Name Time Method