PEPTIDE RECEPTOR RADIONUCLIDE THERAPY WITH 90Y-DOTATOC IN RELAPSED/REFRACTORY DIFFUSE LARGE B CELL AND MANTLE CELL LYMPHOMAS

Phase 1

• Conditions: Relapsed or refractory DLBCL (DIFFUSE LARGE B CELL LYMPHOMAS) or MCL (MANTLE CELL LYMPHOMAS); MedDRA version: 17.0Level: HLGTClassification code 10025320Term: Lymphomas non-Hodgkin's B-cellSystem Organ Class: 10005329 - Blood and lymphatic system disorders; MedDRA version: 17.0Level: HLTClassification code 10026798Term: Mantle cell lymphomasSystem Organ Class: 10005329 - Blood and lymphatic system disorders; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-003418-10-IT
• Lead Sponsor: ISTITUTO SCIENTIFICO ROMAGNOLO PER LO STUDIO E LA CURA DEI TUMORI IRST - IRCCS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-09-23
• Last Update Posted: 12 March 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 35

Inclusion Criteria

1. Male or Female, aged >18 years.
2 . Histologically confirmed relapsed or refractory DLBCL or MCL not suitable to other treatments.
3. Patients with documented disease will be admitted to therapeutic phase only if the diagnostic PET/CT with 68Ga-DOTATOC images demonstrate a significant uptake in the tumour (SSR-positive tumour).
4.Patients must have at least one bidimensional measurable lesion with long axis > 15 mm at CT scan (MRI is allowed only if CT scan cannot be performed), according to Cheson Criteria [48].
5.ECOG performance status = 2.
6.Life expectancy of at least 3 months.
7.Adequate cardiac function (EF >50%) as assessed at echocardiography and ECG.
8.Conserved hematological, liver and renal parameters, and in particular: haemoglobin >= 9 g/dL, absolute neutrophil count (ANC) >= 1.5 x 109 /L, platelets >= 100 x 109 /L, bilirubin =1.5 X UNL (upper normal limit), ALT <2.5 X UNL (< 5 X UNL in presence of liver metastases), creatinine < 2 mg/dL
9.Patients must not have received other treatments with radiopeptides (e.g. 111In-pentetreotide, 177Lu-DOTATATE, 131I-MIBG).
10. If female of childbearing potential, agreement to use adequate contraceptive
methods (e.g., oral contraceptives, condoms, or other adequate barrier
controls, intrauterine contraceptive devices, or sterilization) beginning at
screening visit and continuing until 3 months following last treatment with study
drug. Negative serum pregnancy test for females of childbearing potential within 7
days of starting treatment.

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 18
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 17

Exclusion Criteria

1.Pregnancy/breastfeeding (a pregnancy test not older than 7 days is mandatory).
2.Bone marrow invasion > 25 %.
3.Other concomitant neoplasm (excluding in situ basaliomas and radically treated cervical cancers); subjects must be
free from other neoplasms at least 3 years.
All acute toxic effects of any prior therapy (including surgery radiation therapy,chemotherapy) must have resolved
to a grade <= 1 according to National Cancer Institute Common Terminology Criteria for Adverse Events Version
4.0 (CTCAE).
4.Evidence of myelodysplastic syndrome or other hematologic diseases
5.Patients treated with chemotherapy and therapeutic radiotherapy within 4 weeks.
6.Participation in another clinical trial with any investigational agents within 30 days prior to study screening.
7.Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive
heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit
compliance with study requirements.
8.Positive serology for Hepatitis B (HB) defined as a positive test for Hepatitis B surface antigen (HbsAg). In addition,
if negative for HBsAg but Hepatits B core antibody (HBcAb) positive (regardless of HBsAb status), a HBV DNA test
will be performed and if positive the subject will be excluded.
Any patient with HBcAb positivity will receive anti viral prophylaxis during the study, according to the procedures
suggested by local Hepatology service.
9.History of allergic reactions attributed to compounds of similar chemical or biologic composition.
10.Previous autologous stem cell transplant in the last 2 months.

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 evaluate the overall response rate of Y-PRRT in relapsed or refractory DLBC and MCL NHL, not suitable to other therapies, included HDCT (high dose chemotherapy), or patients relapsed after HDCT with ASCT (Autologous stem cell transplant).;Secondary Objective: The secondary objectives are acute and late toxicity, the type and duration of lymphocyte toxicity, (B, T, NK lymphocytes), progression free survival, overall survival and Quality of Life. ;Primary end point(s): overall response rate of Y-PRRT in relapsed or refractory DLBC and MCL NHL, not suitable to other therapies, included HDCT (high dose chemotherapy), or patients relapsed after HDCT with ASCT (Autologous stem cell transplant).;Timepoint(s) of evaluation of this end point: 24 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Acute and late toxicity, the type and duration of lymphocyte toxicity, (B, T, NK lymphocytes), progression free survival, overall survival and Quality of Life;Timepoint(s) of evaluation of this end point: 12-48 months