Open-label, Dose escalation, followed by Open-label, Single Arm, Multi-center Clinical Trial of HuMax-CD4, a Fully Human Monoclonal Anti-CD4 Antibody, in Patients with Mycosis Fungoides (stage IB-IVB) or Sézary Syndrome who are Refractory or Intolerant to Targretin® (bexarotene) and one other Standard Therapy - HuMax-CD4 in Refractory Mycosis Fungoides or Sézary Syndrome

• Conditions: Refractory Mycosis Fungoides (stage IB-IVB) and Sézary Syndrome.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; MedDRA version: 9.1Level: LLTClassification code 10028508Term: Mycosis fungoides/Sezary syndrome

• Registration Number: EUCTR2006-003353-24-DE
• Lead Sponsor: TenX Biopharma, Inc.,

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2006-12-04
• Last Update Posted: 19 March 2012

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 92

Inclusion Criteria

1) A biopsy compatible with the diagnosis of MF or SS with a CD4 positive phenotype within 6 months of study entry
2) MF stage IB to IVB (highest stage ever) or SS
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. Patients who are intolerant to a therapy and who have had a clinically meaningful response (defined as greater than a 50% reduction in disease) should not be enrolled until disease progression is documented (defined as worsening of the disease by 25% or more compared to the nadir after treatment was discontinued due to intolerance). Side effects/toxicity of Targretin therapy which qualify for the intolerance criteria are isolated hypertriglyceridemia or combined hypertriglyceridemia/hypercholesterolemia despite 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, 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 year

Exclusion Criteria

1. Primary cutaneous anaplastic large cell lymphoma
2. Lymphomatoid papulosis
3. Histopathological evidence of sheets of large cells (from skin or nodes) or poorly
differentiated tumors
4. Prior treatment with Total Skin Electron Beam (TSEB) therapy within six months
5. Prior treatment with Campath (alemtuzumab)
6. Prior treatment with more than three regimens of single agent chemotherapy
7. Prior treatment with pentostatin within 6 months
8. 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, combination chemotherapy, oral retinoids, systemic glucocorticosteroids, carmustine, nitrogen mustard, systemic vitamin A or etretinate
9. Treatment with topical glucocorticosteroids within 2 weeks prior to visit 2
10. 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
11. 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
12. Acute or chronic infectious disease requiring medication. Patients with a history of intermittent relapsing herpes simplex skin affection on prophylactic treatment with acyclovir or valacyclovir and patients taking dicloxillin for carriage of Staphylococcus aureus may be included
13. Significant concurrent, uncontrolled, or active medical condition including, but not limited to renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, cerebral or psychiatric disease
14. 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 > 3 times upper limit of normal
e) S-Creatinine > 1.5 mg/dL
f) CD3+CD4+ cell count > 10,000 cells/mm3
15. Known or suspected positive serology for HIV
16. Known or suspected positive serology for hepatitis B or C
17. Signs or symptoms of CNS involvement
18. 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)
19. Prior treatment with anti-CD4 monoclonal antibodies
20. Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder)
21. Breast feeding women or women with a positive pregnancy test at Visit 1
22. 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
Main Objective: The primary objective is to determine the efficacy of HuMax-CD4 in patients with MF or SS 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 or SS who are refractory or intolerant to treatment with Targretin® and one other standard therapy. ;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