OVSTAR TIL Trial (OVarian Cancer Co-STimulatory Antigen Receptor TIL Trial)
NCT ID: NCT04389229
Last Updated: 2020-12-16
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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WITHDRAWN
PHASE1/PHASE2
INTERVENTIONAL
2020-07-01
2025-07-31
Brief Summary
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Detailed Description
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Patients will receive non-myeloablative lymphodepleting pre-conditioning chemotherapy with cyclophosphamide 600mg/m2/day and fludarabine 30mg/m2/day on Day -5, -4 and -3. Chemotherapy will aim to be delivered as an outpatient, but patients can be admitted if clinically needed. Patients will be required to maintain oral hydration of \>2 litres per day. If this is felt to be difficult to achieve then the patient will be admitted for IV fluids. Patients will be admitted for TIL infusion on Day 0. The TIL infusion will be administered at least 36 hours after last dose of chemotherapy. The cells will only be thawed once an Investigator has made a positive decision to go ahead with infusion and confirmed this in writing. TIL infusion may be delayed for up to 7 days for clinical reasons or for issues regarding the cell specification. This decision must be made before final preparation for infusion. Following TIL infusion, patients will commence subcutaneous interleukin-2 at a fixed dose of 18 million units once a day. Patients must remain an inpatient for the duration of IL-2 treatment for a minimum of 7 days post TIL infusion. Recruitment to the study will occur over approximately 24-month period. Recruitment to CoTIL-01 will commence after UTIL-01. Patients will be followed up in the study for 24 months post TIL infusion.
Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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UTIL-01
Single dose autologous unmodified tumour infiltrating lymphocytes
cyclophosphamide
600mg/m2/day for 3 days ( on day -5, -4, -3)
fludarabine
30mg/m2/day for 3 days ( on day -5, -4, -3)
IL-2 (Proleukin)
Subcutaneous injections at a fixed dose of 18 million units once a day following TIL infusion
Unmodified Tumour Infiltrating Lymphocytes (UTIL-01)
Single dose at 5 x 10\^9 - 5 x 10\^10
CoTIL-01
Single dose autologous gene modified tumour infiltrating lymphocytes
cyclophosphamide
600mg/m2/day for 3 days ( on day -5, -4, -3)
fludarabine
30mg/m2/day for 3 days ( on day -5, -4, -3)
IL-2 (Proleukin)
Subcutaneous injections at a fixed dose of 18 million units once a day following TIL infusion
Gene modified Tumour Infiltrating Lymphocytes (CoTIL-01)
Single dose at 2 x10\^9 (+/- 20%) (engineered TIL)
Interventions
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cyclophosphamide
600mg/m2/day for 3 days ( on day -5, -4, -3)
fludarabine
30mg/m2/day for 3 days ( on day -5, -4, -3)
IL-2 (Proleukin)
Subcutaneous injections at a fixed dose of 18 million units once a day following TIL infusion
Unmodified Tumour Infiltrating Lymphocytes (UTIL-01)
Single dose at 5 x 10\^9 - 5 x 10\^10
Gene modified Tumour Infiltrating Lymphocytes (CoTIL-01)
Single dose at 2 x10\^9 (+/- 20%) (engineered TIL)
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
Patients are eligible to be included in the pre-screening phase of the study only if all of the following criteria apply:
1. Women with histologically confirmed recurrent metastatic platinum-resistant high-grade serous ovarian cancer (HGSOC) (platinum resistant defined as progressing within 6 months of last platinum-containing combination chemotherapy. Patients must have received at least 1 line of prior platinum-containing combination chemotherapy and have completed at least 4 cycles of this treatment).
2. Expected to fulfil all entry criteria for OVSTAR Main Study
3. Written informed consent to Pre-Screening
4. Measurable disease by Response Evaluation Criteria in Solid Tumours 1.1
5. Have disease suitable for fresh TIL harvesting from tumour biopsies (only applicable to patients who are not participants of Sponsor's Tumour Collection Programme, PRIME)
6. Medically suitable for a general anaesthetic and surgical biopsy (only applicable to patients who are not participants of Sponsor's Tumour Collection Programme, PRIME)
7. Women of child bearing potential must be willing to practise a highly effective method of birth control once consented to pre-screening
8. World Health Organisation (WHO) Performance Status of 0 or 1 (Appendix 3)
9. Age equal to or greater than 18 years
10. Life expectancy \> 6 months
11. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the Pre-Screening or Main Study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
12. Seronegative for HIV antibody, Hep B antigen, Hep C antibody and syphilis
13. Haematological and biochemical indices
1. Women with metastatic platinum resistant high-grade serous ovarian cancer (HGSOC) who have recurrent disease (platinum resistant defined as progressing within 6 months of last platinum-containing combination chemotherapy. patients must have received at least 1 line of prior platinum-containing combination chemotherapy and have completed at least 4 cycles of this treatment).
2. Informed consent to Main Study
3. Confirmation from Sponsor of successful TIL growth
4. Measurable disease (by Response Evaluation Criteria in Solid Tumors 1.1) on CT within 4 weeks of main study entry
5. Left ventricular ejection fraction \>50% on Echocardiogram scan
6. Patients must be willing to practice a highly effective method of birth control during treatment and for four months after receiving the preparative regime if appropriate.
7. World Health Organisation (WHO) Performance Status of 0 or 1 (Appendix 3)
8. Age equal to or greater than 18 years
9. Life expectancy \> 6 months
10. Absence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the Pre-Screening or Main Study protocol and follow-up schedule; those conditions should be discussed with the patient before registration in the trial
11. Seronegative for HIV antibody, Hep B antigen, Hep C antibody and syphilis
12. Haematological and biochemical indices
Exclusion for Main Study
1. Patients receiving day 1 of their last cycle of chemotherapy or targeted therapy less than four weeks prior to pre-conditioning chemotherapy.
2. Patients receiving systemic immunosuppressive therapy including steroids at doses higher than 10mg/day of prednisolone (or equivalent) within four weeks of commencing pre-conditioning chemotherapy (unless this is required briefly as anti-emetic prophylaxis for the treatments detailed in above point 1). Patients who require such therapies intermittently due to pre-existing disorders are also excluded.
3. Patients who have any malignant or likely malignant Central Nervous System (CNS) lesion visible on CT.
4. Evidence of any active significant infection.
5. Evidence of clinically significant immunosuppression such as primary immunodeficiency (e.g. severe combined immunodeficiency disease).
6. Clinically significant cardiac disease. Examples would include unstable coronary artery disease, myocardial infarction within 6 months or class III or IV American Heart Association criteria for heart disease.
7. Patients who are at high medical risk because of non-malignant systemic disease including those with uncontrolled cardiac or respiratory disease, or other serious medical or psychiatric disorders which, in the lead clinician's opinion, would not make the patient a good candidate for adoptive TIL therapy.
8. Severe and active autoimmune disease.
9. Receiving concomitant treatment with any other experimental drugs within 4 weeks of pre-conditioning chemotherapy. Patients receiving experimental immunotherapies will be discussed with the sponsor.
10. Patients not considered likely to comply with required follow up.
11. Patients with severe allergies, history of anaphylaxis or known allergies to the administered drugs.
12. Patients who are pregnant or breast feeding should be excluded from entering the study
13. Patients who have received any prior adoptive cell therapy or organ transplant (including stem cells).
14. Caution should be exercised for patients requiring regular drainage of ascites or pleural effusions. When there is sufficient fluid to be safely drained, drainage must be performed prior to trial enrolment and pre-conditioning chemotherapy in those patients.
15. Patients with any contraindications to any of the components of the study Non Investigational Medicinal Products (cyclophosphamide, fludarabine, Interleukin-2) will be excluded
16. Patents who have received live vaccines within 4 weeks prior to TIL therapy will be excluded.
Exclusion Criteria
Patients will not be invited to participate in Pre-Screening if any of the following criteria apply:
1. History of a previous malignancy at another site, unless followed for \>2 years with no sign of recurrent disease (local completely excised cutaneous basal cell, squamous cell carcinoma or in situ carcinoma will be allowed).
2. Patients receiving chemotherapy, targeted therapy, immunotherapy or systemic steroids including steroid doses \>10mg/day of prednisolone (or equivalent) during the previous four weeks prior to TIL harvesting. Patients who require such therapies intermittently due to pre-existing disorders are also excluded.
3. Evidence of any active significant infection.
4. Patients who have any malignant or likely malignant Central Nervous System (CNS) lesion visible on CT.
5. Evidence of clinically significant immunosuppression such as primary immunodeficiency (e.g. severe combined immunodeficiency disease).
6. Clinically significant cardiac disease. Examples would include unstable coronary artery disease, myocardial infarction within 6 months or class III or IV American Heart Association criteria for heart disease.
7. Patients who are at high medical risk because of non-malignant systemic disease including those with uncontrolled cardiac or respiratory disease, or other serious medical or psychiatric disorders which, in the lead clinician's opinion, would not make the patient a good candidate for adoptive TIL therapy.
8. Severe and active autoimmune disease.
9. On concomitant treatment with other experimental drugs within 4 weeks of TIL harvesting.
10. Patients not considered likely to comply with required follow up.
11. Patients with severe allergies, history of anaphylaxis or known allergies to the administered drugs.
12. Patients who have received any prior adoptive cell therapy or organ transplant (including stem cells).
13. Patients who are pregnant or breast feeding should be excluded from pre-screening
14. Patients with any contraindications to any of the components of the study Non Investigational Medicinal Products (cyclophosphamide, fludarabine, Interleukin-2) will be excluded
15. Patents who have received live vaccines within 4 weeks prior to TIL therapy will be excluded
Inclusion for Main Study
18 Years
FEMALE
No
Sponsors
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Immetacyte Ltd
INDUSTRY
Responsible Party
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Principal Investigators
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Fiona Thistlethwaite, PhD, MRCP
Role: PRINCIPAL_INVESTIGATOR
The Christie Hospital
Locations
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Queens Elizabeth Hospital
Birmingham, , United Kingdom
The Christies Hospital
Manchester, , United Kingdom
Countries
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Other Identifiers
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2019-000106-30
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
IMM-2019T-01-OC
Identifier Type: -
Identifier Source: org_study_id