A Phase I/II open label study to assess efficacy and safety of IPH1101 associated with low dose of interleukin 2, as add-on therapy to imatinib in CML patients with residual molecular disease

• Register: EUCTR
• Last refreshed on: 19 March 2012
• Main ID: EUCTR2007-004252-37-FR
• Date of registration: 27/08/2007
• Prospective Registration: Yes
• Primary sponsor: Innate Pharma
• Public title: A Phase I/II open label study to assess efficacy and safety of IPH1101 associated with low dose of interleukin 2, as add-on therapy to imatinib in CML patients with residual molecular disease
• Scientific title: A Phase I/II open label study to assess efficacy and safety of IPH1101 associated with low dose of interleukin 2, as add-on therapy to imatinib in CML patients with residual molecular disease
• Date of first enrolment: 11/10/2007
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-004252-37
• 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

France

Key inclusion & exclusion criteria

Inclusion criteria:
1) Signed informed consent prior to any protocol-specific procedures
2) BCR-ABL positive CML treated with first line imatinib as follow:
At least 2 years of treatment with imatinib,
At least 3 months since any imatinib dosage modification,
3) Complete cytogenetic response ((CCR) confirmed by recent cytogenetic analysis < 6 months)
4) Bcr-Abl/Abl ratio measured by qRT-PCR in blood (according to the european recommendations) between = 1% and > 0,001% within 3 months prior to inclusion.
5) Dosage of imatinib at screening and pre-inclusion within the range 800ng/ml – 1800ng/ml
6) Aged over 18 years
7) Adequate bone marrow, hepatic and renal function as follows:
- Lymphocytes > or = 900/µl
- Platelets > or =100 x 10E9/l,
- Total bilirubin < or = 2 x upper limit normal (ULN)
- Transaminases (AST [SGOT]; ALT SGPT]) < ou = 3 x ULN
- Serum creatinine < or = 2 x ULN
8) Normal thyroid function ( 0,15< TSH<5mU/l)
9) QTc interval duration < 430 ms for men, < 450 ms for women
10) At least 2 weeks since previous surgery
11) Male or female patient who accepts and is able to use recognised highly effective contraception (oral contraceptives, intrauterine contraceptive device, barrier method of contraception in conjunction with spermicidal jelly, or surgically sterile) throughout the study.

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) Pregnant or lactating women
2) Concurrent treatment with any other anti-cancer therapy or any forbidden concomitant treatments:
- Biphosphonates and immunosuppressive agents,
- Systemic and chronic inhaled steroids,
- Beta-blockers and calcium channel blockers
3) Participation in another clinical trial with any investigative drug within 30 days prior to study randomisation
4) Prior history of high dose chemotherapy followed by bone marrow or peripheral stem cell support or presence of a transplanted solid organ (with the exception of a corneal transplant > 3 months prior to study inclusion)
5) Any known hypersensitivity to one of the study treatments
6. Current active infection
7) Serious concurrent uncontrolled medical disorder such as diabetes, autoimmune disease,
8) Severe viral infection HIV, HCV, HBV (HBsAg)
9) 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 arrythmia requiring treatment or fulfil any other exclusion criteria,
- Myocardial infarction within the previous 6 months, or
- Symptomatic cardiac arrhythmia requiring treatment,
10) History of another malignancy within the past 5 years, except basal cell carcinoma of the skin or carcinoma in situ of the cervix,
11) 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 request for inclusionin the trial.



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

Health Condition(s) or Problem(s) studied

Chronic Myeloid Leukemia
MedDRA version: 9.1 Level: LLT Classification code 10009700 Term: CML

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 18 MUI
Product Name: PROLEUKIN 18 MUI
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: aldesleuskin
CAS Number: 110942024
Concentration unit: million IU million international units
Concentration type: equal
Concentration number: 18-

Primary Outcome(s)

Secondary Objective: The secondary objectives are:
- To determine the safety of IPH1101/ IL-2 low dose association in combination with imatinib
- To assess the biological activity of the combination
- To investigate the relationship between biological activity and efficacy of the combination.
- To determine the duration of effect (complete molecular response)
- To document the rate of progression free survival

Main Objective: The primary objective is to assess the efficacy of IPH1101 associated with low dose of IL-2 as add-on therapy to imatinib in CML patients with residual molecular disease after at least 2 years of imatinib monotherapy.

Primary end point(s): The primary endpoint will be the rate of patients achieving a complete molecular response (Bcr-Abl/Abl < 0.001%) within 24 weeks and confirmed on second determination 3 weeks later. The primary efficacy analysis will be performed on the population of evaluable patients.
Patients evaluable for primary efficacy criteria will be defined as follows:
Patients who receive at least one adequate cycle of IPH1101 associated with low dose of IL-2 and are evaluated for Bcr-Abl plasma level until at least 24 weeks.

Secondary ID(s)

IPH1101-204