A study to identify the most effective dose of Betalutin in patients with a type of follicular lymphoma that is CD37-positive which has recurred

Conditions: Relapsed CD37+ non-Hodgkin B-cell follicular lymphoma
MedDRA version: 18.0Level: PTClassification code 10029547Term: Non-Hodgkin's lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA version: 18.0Level: PTClassification code 10003902Term: B-cell lymphoma recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Registration Number: EUCTR2015-001570-17-HU

Lead Sponsor: ordic Nanovector ASA

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 125

Inclusion Criteria

1. Histologically confirmed (by World Health Organization [WHO] classification) follicular lymphoma (follicular grade I-IIIA)

2. Relapsed after 2 or more prior systemic regimens

3. Requiring initiation of treatment for the NHL

4. Age =18 years

5. ECOG performance status of 0-2

6. Life expectancy of at least 3 months

7. Bone marrow tumour infiltration <25% tumour cells

8. CD37-positive; re-biopsy or test existing tumour material if not known

9. Negative HAMA test

10. Laboratory values within 15 days before study enrolment:
a) Absolute Neutrophil Counts = 1.5 x 109/l
b) Platelet count = 150 x 109 /l
c) Total bilirubin = 1.5 x upper limit of normal
d) Alkaline Phosphatase = 4x normal level
e) ALAT = 4x normal level
f) Creatinine =110 µmol/L (men), 90 µmol/L (women)

11. Presence of radiographically measurable lymphadenopathy or extranodal lymphoid malignancy (according to standard criteria: at least one bi-dimensionally measurable lesion (>1.5 cm in its largest dimension by CT scan).

12. Women of childbearing potential must:
a. understand that the study medication is expected to have teratogenic risk
b. have a negative serum pregnancy test at screening and before Betalutin injection
c. commit to continued abstinence from heterosexual intercourse or begin two acceptable methods of birth control with a Pearl-Index = 1%. without interruption, 4 weeks before starting study drug, throughout study drug therapy and for 5 months after end of study drug therapy, even if she has amenorrhoea

13. Male subjects must agree to use condoms during intercourse throughout study drug therapy and the following 5 months

14. The patient has been fully informed about the study and has signed the informed consent form

15. The patient is willing and able to comply with the protocol and agrees to return to the hospital for follow-up visits and examination
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 95
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

1. Evidence of severe or uncontrolled systemic diseases:
a) Uncontrolled infection including evidence of ongoing systemic bacterial, fungal, or viral infection (excluding viral upper respiratory tract infections) at the time of initiation of study treatment
b) Known to be HIV positive
c) Pulmonary conditions e.g. unstable or uncompensated respiratoryd) Hepatic conditions
e) Renal conditions
f) Neurological conditions
g) Psychiatric conditions
h) Metabolic conditions
i) History of erythema multiforme, toxic epidermal necrolysis or Stevens-Johnson syndrome
j) Cardiac conditions, including
i. History of acute coronary syndromes (including unstable angina), coronary angioplasty, or stenting within the past 24 weeks
ii. Class II, III, or IV heart failure as defined by the New York Heart Association (NYHA) functional classification system
iii. Known uncontrolled arrhythmias (except sinus arrhythmia) in the past 24 weeks.

2. Bulky disease defined as the presence of one or more nodes with at least one dimension of 10 cm or more.

3. Ongoing immunosuppressive therapy, including systemic corticosteroids. Patients may be using topical or inhaled corticosteroids

4. Known or suspected central nervous system involvement of lymphoma

5. Previous total body irradiation, or irradiation of >25% of the patient’s bone marrow

6. Investigational drug, chemotherapy, or immunotherapy received within the last 4 weeks prior to start of study treatment, except for the pre-treatment used in this study

7. Pregnant or lactating women

8. Prior hematopoietic allogenic stem cell transplantation

9. Prior autologous stem cell transplantation =2 years ago

10. History of a non-lymphoma malignancy except for the following:
a) adequately treated local basal cell or squamous cell carcinoma of the skin
b) cervical carcinoma in situ
c) superficial bladder cancer
d) localized prostate cancer
e) other adequately treated Stage 1 or 2 cancer currently in complete remission
f) or any other cancer that has been in complete remission for = 5 years

11. Allergy to X ray contrast agents

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: ? Part 1: To identify the optimal dose of Betalutin in terms of overall response rate (ORR), assessed with the use of standard criteria for Lymphoma.<br><br>? Part 2: To assess the ORR assessed with the use of standard criteria for Lymphoma;Secondary Objective: ? To assess the best overall response rate<br>? To assess the duration of response <br>? To estimate progression free survival (PFS) <br>? To assess the time to next treatment <br>? To estimate overall survival (OS) <br>? To investigate Quality of Life (QoL) <br>? To investigate safety and toxicity of Betalutin;Primary end point(s): Overall response rate (ORR), defined as the proportion of patients who achieve a complete response (CR) or partial response (PR) assessed with the use of standard criteria for lymphoma; in part 2 of the study, responses will be assessed by the independent image review committee. ORR scored at 3 months will be used for primary efficacy end-point.;Timepoint(s) of evaluation of this end point: At 3 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1) Best overall response rate<br><br>2) Duration of tumour response (DOR)<br><br>3) PFS (Performance Status)<br><br>4) Time to next treatment<br><br>5) OS (Overall Survival);Timepoint(s) of evaluation of this end point: 1) 5 years<br><br>2) Time from the date of the onset of response to the first documentation of relapse or progressive disease, whichever occurs first.<br><br>3) Defined as the interval from Betalutin administration and date of: relapse (new or enlarged lesions after CR); progression (new or enlarged lesions after PR or stable disease [SD]), or death from any cause. If none of the above events are observed, PFS should be censored at the date of the last assessment (i.e. last CT scan). Cheson criteria is used for definition of new or enlarged lesion.<br><br>4) The time from Betalutin administration to the start of the next anti-cancer therapy.<br><br>5) From the date of study entry until the date of death of any cause.

Related Trials