Investigating the most appropriate dose and effectiveness of thiotepa in combination with ifosphamide, etoposide and rituximab in patients with lymphoma arising in the brain or spinal cord

Phase 1

Completed

• Conditions: Primary central nervous system lymphoma; Cancer

• Registration Number: ISRCTN12857473
• Lead Sponsor: niversity of Birmingham

Brief Summary

2021 Results article in https://pubmed.ncbi.nlm.nih.gov/34464973/ (added 15/02/2023)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-12-03
• Study Completion: 2021-10-31
• Last Update Posted: 27 February 2023

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

1 Age = 16 years of age
2. Histologically confirmed* CD20+ Diffuse Large B Cell 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

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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> MTD of thiotepa in combination with ifosphamide, etoposide and rituximab (TIER)<br> Timepoint(s): End of 2 cycles of treatment<br>

Secondary Outcome Measures

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