A phase I/II open label study of IPH1101 (with low dose of interleukin-2 [IL-2]) in combination with rituximab re-treatment in patients with Follicular Lymphoma.

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2006-006891-39-DE
• Date of registration: 13/09/2007
• Prospective Registration: Yes
• Primary sponsor: Innate Pharma S.A.
• Public title: A phase I/II open label study of IPH1101 (with low dose of interleukin-2 [IL-2]) in combination with rituximab re-treatment in patients with Follicular Lymphoma.
• Scientific title: A phase I/II open label study of IPH1101 (with low dose of interleukin-2 [IL-2]) in combination with rituximab re-treatment in patients with Follicular Lymphoma.
• Date of first enrolment: 30/11/2007
• Target sample size: 55
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2006-006891-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other:

Countries of recruitment

Belgium, Germany

Key inclusion & exclusion criteria

Inclusion criteria:
1. Signed informed consent prior to any protocol-specific procedures,
2. Histologicy documented diagnosis of follicular non-Hodgkin’s lymphoma,
3. Follicular lymphoma of grade 1 or 2 (WHO [World Health Organisation] classification),
Note: 3a patients will also be allowed, but only if the absence of transformation to high grade lymphoma was documented by a lymph-node biopsy done at Screening.
4. Progression after one, two, three or four previous line(s) of therapy,
5. At least one but not more than two of the prior line(s) of therapy must have been a rituximab-containing treatment,
6. At least 4 weeks from Screening since previous systemic anti-cancer therapy, including steroids,
7. Interval at Screening from last administration of previous systemic therapy for fludarabin-, rituximab- or ibritumomab tiuxetan-containing therapies, or autologous therapy with auto transplantation:
- 6 months in case of fludarabine-containing treatment or autologous therapy with auto transplantation,
- 6 months in case of rituximab-containing chemotherapy or ibritumomab tiuxetan,
- maintenance therapy accepted, with the same 6-month clearance period.
8. Measurable disease evaluable by Cheson et al. 1999 criteria 2
9. At least 2 weeks from Screening since previous surgery,
10. Aged > 18 years and = 75 years,
11. Eastern Cooperative Oncology Group (ECOG) performance status = 1 (i.e. 0, or 1),
12. Adequate bone marrow, hepatic and renal function as follows:
- White blood cells (WBC) = 3.5 x 109/L, neutrophils = 1 x109/L, lymphocytes > 1 x 109/L,
- Platelets = 60 x 109/L,
- Haemoglobin = 8 g/dL or 5.6 mmol/L,
- Total bilirubin = 2 x upper limit normal (ULN) and transaminases (alanine amino transferase / serum glutamic pyruvic transaminase [ALT / SGPT]; aspartate amino transferase /serum glutamic oxalo-acetic transaminase [AST / SGOT]) = 3 x ULN,
OR if liver metastases, total bilirubin and transaminases = 5 x ULN,
- Serum creatinine = 2 x ULN,
- Alkaline Phosphatase (ALP) = 3 x ULN,
13. Electrocardiogram (ECG) QTc interval duration < 430 ms for men, < 450 ms for women,
14. Patient may have received prior radiotherapy but not for the treatment of lesions that will be used to assess efficacy. A minimum of 4 weeks must have elapsed prior to Screening.
15. Patients (male and female) who accept and are able to use recognised highly effective contraception methods (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly, or surgically sterile) throughout the study and up to 12 months after last dose of study drug, if applicable,
16. Life expectancy >12 weeks.
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

Exclusion criteria:
1. Any mass > 7 cm,
2. Pleural or peritoneal effusion,
3. Non easily measurable disease such as: isolated
- mesenteric panniculitis,
- bone marrow infiltration,
- bone lytic lesion,
- epiduritis,
- cutaneous follicular lymphoma.
4. LDH > ULN,
Note: patients with LDH > ULN from 1.0 to 2.0 ULN will also be allowed, but only if the absence of transformation to high grade lymphoma was documented by a lymph-node biopsy performed at Screening.
5. Transformation to high grade lymphoma (secondary to low grade lymphoma),
Note: If the investigator suspects transformation by clinical examination, a repeat lymph-node biopsy will be required prior to enrolment to document the absence of transformation.
6. Pregnant or lactating women,
7. Human immuno-deficiency virus (HIV), hepatitis C virus (HCV) or hepatitis B virus (HBV) positive serology at Screening,
8. Concurrent treatment with any other anti-cancer therapy or with other experimental drugs, participation in another clinical study with any investigative drug within 30 days prior to study Screening,
9. Concurrent treatment with:
- biphosphonates,
- immunosuppressive agents,
- anticancer hormonal therapy,
- systemic and chronic inhaled steroids,
- beta-blockers and calcium channel blockers.
10. Prior history of high-dose chemotherapy followed by allogenic bone marrow or peripheral stem cell support/transplant, or presence of a transplanted solid organ (with the exception of a corneal transplant > 3 months prior to study Screening),
11. Prior history of mini-allogenic bone marrow transplantations,
12. Any known hypersensitivity to one of the study treatments,
13. Current active infection; serious concurrent, uncontrolled medical disorder such as diabetes, autoimmune disease, etc (at investigator’s discretion),
14. Cardiovascular disease:
- Stage III or IV congestive heart failure (CHF) as determined by the New York Heart Association (NYHA) classification system for heart failure.
Note: patients with NYHA stage I or II CHF may be included provided they do not have arrhythmia requiring treatment or fulfil any other exclusion criteria.
- Myocardial infarction within the previous 6 months, or
- Symptomatic cardiac arrhythmia requiring treatment,
15. Left ventricular ejection fraction < 45% (as assessed by Multiple Gated Acquisition Scan [MUGA scan] or cardiac ultrasonography),
16. History of another malignancy within the past 5 years, except basal cell carcinoma of the skin or in situ cervix carcinoma,
17. Any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be assessed with the patient before requesting for enrolment in the study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Follicular Lymphoma
MedDRA version: 9.1 Level: LLT Classification code 10029473 Term: Nodular (follicular) lymphoma

Intervention(s)

Product Name: Phosphostim 200
Product Code: IPH1101
Pharmaceutical Form: Powder for solution for infusion
CAS Number: 876060-87-6
Current Sponsor code: IPH1101
Other descriptive name: bromohydrin pyrophosphate (BrHPP)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Trade Name: Proleukin S 18x106 IE
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: aldesleukin
Concentration unit: million IU million international units
Concentration type: equal
Concentration number: 18-

Trade Name: MabThera 100mg
Product Name: MabThera 100mg
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: rituximab
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Trade Name: MabThera 500mg
Product Name: MabThera 500mg
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: rituximab
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Secondary Objective: - Evaluate other clinical efficacy parameters,
- Evaluate the biological activity of IPH1101 (with low-dose aldesleukin) in this schedule and setting,
- Investigate the relationship between biological activity and clinical efficacy,
- Determine the safety of IPH1101 (with low dose aldesleukin) in this schedule and setting,
- Evaluate the in vitro response to BrHPP stimulation of Vgamma9Vdelta2 human T lymphocytes (gamma delta T cells) from patients progressing after rituximab therapy and to explore its potential relationship with biological activity and clinical efficacy.

Main Objective: The primary objective of this study is to assess the clinical efficacy of IPH1101 (with low-dose IL 2, as aldesleukin), administered in combination with a standard course of rituximab, in patients with Follicular Lymphoma having relapsed after at least one prior rituximab-containing line.

Primary end point(s): The primary endpoint will be the overall response rate (ORR), measured during the 24 weeks of study. The primary efficacy analysis will be performed on the population of evaluable patients, and also, among a sub-population of evaluable patients who have a greater than two-fold gamma delta T cells in vivo amplification rate (including patients of the group of the Phase I like period having received the same doses as patients of Period 2).

Secondary ID(s)

IPH1101-202

2006-006891-39-BE