Condition category
Cancer
Date applied
03/12/2014
Date assigned
03/12/2014
Last edited
29/04/2015
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Scientific

Primary contact

Ms Kathryn Paterson

ORCID ID

Contact details

Cancer Research UK Clinical Trials Unit
School of Cancer Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

17668

Study information

Scientific title

A Phase I/II study of thiotepa, ifosphamide, etoposide and rituximab for the treatment of relapsed or refractory primary central nervous system lymphoma

Acronym

Study hypothesis

The phase I dose finding component is a 3+3 cohort design which will recruit up to 18 patients in order to find the MTD of thiotepa in combination with ifosphamide, etoposide and rituximab (TIER). All patients recruited into phase I at the MTD will also contribute towards phase II. The phase II study is based on an A'hern’s design design to assess the activity of thiotepa in combination with ifosphamide, etoposide and rituximab (TIER). 28 patients will be recruited in total in phase II (including some patients from phase I).

Ethics approval

14/LO/1568; First MREC approval date

Study design

Non-randomised, interventional

Primary study design

Interventional

Secondary study design

Non randomised study

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Topic: Cancer; Subtopic: Lymphoma; Disease: Lymphoma (non-Hodgkin's)

Intervention

Etoposide, 250mg/m2 day 2 of 21 day cycle; Ifosphamide, 2g/m2/day days 2-4 for each 21 day cycle.; Rituximab, 375mg/m2/day days 1-2 for each 21 day cycle; Thiotepa, Chemotherapy (doses 20mg/m2 - 50mg/m2)

Intervention type

Drug

Phase

Drug names

1. Etoposide
2. Ifosphamide
3. Rituximab
4. Thiotepa

Primary outcome measures

MTD of thiotepa in combination with ifosphamide, etoposide and rituximab (TIER)
Timepoint(s): End of 2 cycles of treatment

Secondary outcome measures

1. 2 year event free survival (EFS); Timepoint(s): 2 years after trial treatment
2. 2 year overall survival (OS); Timepoint(s): 2 years after trial treatment
3. 2 year progression free survival (PFS); Timepoint(s): 2 years after trial treatment
4. CR rate after 2 cycles of TIER; Timepoint(s): End of 2 cycles of treatment
5. Overall response rate (Complete Response (CR) + Complete Response: unconfirmed (CRu) + Partial Res; Timepoint(s): end of 2 cycles of treatment
6. Proportion of patients proceeding to high-dose therapy and autologous stem cell transplant (HDT-AS; Timepoint(s): Following trial treatment
7. Rate of successful stem cell harvest; Timepoint(s): After completing trial treatment
8. Toxicity of TIER using the National Cancer Institute Common Terminology Criteria for Adverse Event; Timepoint(s): All cycles of trial treatment

Overall trial start date

12/12/2014

Overall trial end date

17/11/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1 Age ≥ 16 years of age
2. Histologically confirmed* CD20+ Diffuse Large BCell
Lymphoma (DLBCL) confined to the central nervous system
3. Relapsed or refractory primary central nervous system lymphoma (PCNSL) according to the following definition :
3.1. One or two prior chemotherapy regimen(s), of which at least one regimen contained highdose
methotrexate at a dose of >1g/m2.
3.2. Minimum of one cycle containing highdose methotrexate
4. ECOG performance status 0,1 or 2 (or 3 if attributed to lymphoma)
5. Adequate organ function:
5.1. Bone marrow: platelets >80 x109/L, neutrophils >1 x109/L, haemoglobin >80 g/L
5.2. Hepatic: bilirubin <1.5 x upper limit of normal (ULN) (unless isolated unconjugated hyperbilirubinaemia attributable to Gilbert’s syndrome)
5.3. Renal: eGFR ≥40ml/min (Cockcroft-Gault)
5.4. Cardiorespiratory (as judged by the Local Investigator): clinically relevant cardiac or pulmonary function tests must be performed if there is a previous history of significant cardiac or pulmonary impairment
6. Able to comply with the scanning requirements of the study
7. Valid Informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 40; UK Sample Size: 40

Participant exclusion criteria

1. Systemic involvement with lymphoma
2. Active infection requiring intravenous antimicrobials
3. Chemotherapy for lymphoma within 4 weeks registration
4. Wholebrain radiotherapy within 6 months of registration
5. Relapse within 1 year of a Thiotepabased autologous stem cell transplant
6. Prior therapy with the RIE (Rituximab – ifosphamide and etoposide) regimen
7. Evidence of HIV or Hepatitis C infection
8. Hepatitis B infection*
9. Serum albumin <25g/l
10. Pregnant and lactating patients (patients of childbearing potential must have a negative pregnancy test prior to study entry)
11. Competent pPatients and competent patients with partners of childbearing potential not willing to use effective contraception during and for 12 months after therapy

Recruitment start date

12/12/2014

Recruitment end date

17/11/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Cancer Research UK Clinical Trials Unit
School of Cancer Sciences University of Birmingham Edgbaston
Birmingham
B15 2TT
United Kingdom

Sponsor information

Organisation

University of Birmingham

Sponsor details

Cancer Research UK Clinical Trials Unit
Institute for Cancer Studies
Edgbaston
Birmingham
B15 2TT
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

Leukaemia and Lymphoma Research

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes