A study to see if Gemtuzumab Ozogamicin is a useful treatment for patients with Haemophagocytic lymphohistiocytosis (HLH) or Macrophage activation syndrome (MAS) or cancer that has come back (relapsed) or has not responded (refractory) to treatment.

Phase 1

• Conditions: Haemophagocytic lymphohistiocytosis (HLH) or Macrophage activation syndrome (MAS) and relapsed/refractory solid tumours; MedDRA version: 21.1Level: PTClassification code 10071583Term: Haemophagocytic lymphohistiocytosisSystem Organ Class: 10021428 - Immune system disorders; MedDRA version: 21.1Level: LLTClassification code 10053867Term: Macrophage activation syndromeSystem Organ Class: 10021428 - Immune system disorders; MedDRA version: 20.0Level: LLTClassification code 10007050Term: CancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2020-002428-36-GB
• Lead Sponsor: niversity of Birmingham

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2020-09-18
• Last Update Posted: 23 November 2020

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

•Aged >1 year old at the time of trial entry
•Diagnosis of HLH or MAS disease primary, secondary or refractory to treatment at time of enrolment
OR
Histologically confirmed diagnosis of solid cancer with radiological or clinical evidence of disease progression (during or after completion of at least one previous treatment) or any subsequent recurrence (biopsy at relapse is not mandated)
•Must have adequate liver function (solid cancer patients only):
o Total bilirubin = x2 upper limit of normal (ULN)
o Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) = 2.5 x ULN
•Documented negative pregnancy test for female patients of childbearing potential within 7 days prior to trial entry
•Sexually active patients must agree to use 2 methods of adequate and appropriate contraception while on trial drug and for 4 months (male) and 7 months (female) following treatment discontinuation
•Written informed consent given by patient and/or parents/legal guardian

Are the trial subjects under 18? yes
Number of subjects for this age range: 10
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 9
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion Criteria

•Evidence of sinusoidal obstruction syndrome (SOS) / veno-occlusive disease (VOD)
•Previous treatment with another CD33 targeting antibody or immunotoxin
•Hypersensitivity to Gemtuzumab Ozogamicin or to any of the excipients
•Pregnant or lactating female

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To see if gemtuzumab ozogamicin can reduce the number of CD33 myeloid cells in two groups of people 1) who have Haemophagocytic lymphohistiocytosis (HLH) or Macrophage activation syndrome (MAS), or 2)solid tumours which have not responded to previous treatment (refractory) or come back after previous treatment (relapsed). <br><br>;Secondary Objective: To assess the effect of gemtuzumab ozogamicin on overall survival time (OS) and progression free survival time (PFS) (PFS is applicable only to those patients with relapsed/refractory solid tumours).<br><br>To assess the feasibility of delivering gemtuzumab ozogamicin in these patient groups. <br>;Primary end point(s): CD33+ cell count in the blood samples of patients collected at the pre-specified time points (day 1, day 8, day 15, day 22 and 29);Timepoint(s) of evaluation of this end point: CD33+ cell count will be assessed on days 1, 8, 15, 22 and 29.

Secondary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: Overall survival (OS) time is defined as the time from the date of entry into the trial to the date of death. Patients lost to follow-up will be censored accordingly at date last seen. <br>Progression free survival (PFS) time (Patients with solid tumours only) is defined as the time from the date of entry into the trial to the date of disease progression. Patients lost to follow-up will be censored accordingly at date last seen. <br>Incidence of grade 3 and 4 adverse events is the frequency of adverse events (as defined in the protocol).<br>;Secondary end point(s): Overall Survival (OS) time<br>Progression Free Survival (PFS) time (Patients with solid tumours only) <br>Incidence of grade 3 and 4 adverse events<br>