HOVON 164 HL: Tislelizumab plus Gemcitabine and Cisplatin for Relapsed or Refractory Hodgkin Lymphoma followed by Tislelizumab Consolidation in Patients in Metabolic Complete Remission (TIGERR-HL). An open label phase II trial.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

14 Jul 2023 → ongoing

Decision date (initial)

2023-04-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

BeiGene

External identifiers

EU CT number

2022-502225-17-00

ClinicalTrials.gov

NCT05502250

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

To evaluate the efficacy of salvage treatment with gemcitabine and cisplatin (GP) in combination with tislelizumab, followed by tislelizumab consolidation in patients with R/R HL, in terms of progression free survival (PFS) at two years after registration.

Secondary objectives 5

1. To evaluate the overall response rate (ORR: mCR and mPR) after 2 and 4 cycles of GP chemotherapy + tislelizumab salvage treatment.
2. To assess the safety and tolerability of tislelizumab in combination with GP chemotherapy
3. To assess the safety and tolerability of tislelizumab consolidation treatment.
4. To evaluate efficacy in terms EFS from registration, DFS from start of consolidation therapy, and OS from registration with this treatment regimen.
5. To evaluate the predictive value of FDG-PET/CT result after 2 cycles of re-induction for PFS.

Conditions and MedDRA coding

Hodgkin lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

1. Histologically confirmed classical HL (according to the latest version of the WHO classification).
2. Primary refractory to first line chemotherapy, or in first relapse after any polychemotherapy regimen (e.g. ABVD, baseline BEACOPP or escalated BEACOPP, or other induction regimens).
3. In case of relapse, the relapse must be histologically confirmed. In case histologic biopsy is not possible, at least confirmation of the relapse by fine needle aspirate (FNA) or sequential imaging is required.
4. Measurable disease, based on Lugano criteria 2014 [40]; i.e. CT scans showing at least 2 or more clearly demarcated lesions with a long axis ≥ 1.5 cm and a short axis diameter ≥ 1.0 cm, or 1 clearly demarcated lesion with a long axis ≥ 2.0 cm and a short axis diameter ≥ 1.0 cm. These lesions must be FDG-PET-positive.
5. Age 18-70 years inclusive.
6. WHO/ECOG Performance Status ≤ 1
7. No major organ dysfunction, unless HL-related: - Total bilirubin < 1.5x ULN (unless due to lymphoma involvement of the liver or a known history of Gilbert’s syndrome; in that case bilirubin may be elevated up to 3 x ULN). - ALT/AST < 3x ULN (unless due to lymphoma involvement of the liver; in that case ALT/AST may be elevated up to 5 x ULN). - GFR > 60 ml/min as estimated by the Cockcroft&Gault formula.
8. Adequate BM function defined as: - Absolute neutrophil count ≥ 1.5x109/L, unless caused by diffuse bone marrow infiltration by the HL. - Platelets ≥ 75 x109/L, unless caused by diffuse bone marrow infiltration by the HL. - Hemoglobin must be ≥ 8 g/dL (5 mmol/L).
9. Resolution of toxicities from first-line therapy.
10. Able to adhere to the study visit schedule and other protocol requirements.
11. Negative pregnancy test at study entry.
12. Female patient is either post-menopausal for at least 1 year before the screening visit or surgically sterile or if of childbearing potential, agrees to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through at least 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse.
13. Male patient, even if surgically sterilized, (i.e., status post vasectomy) agrees to practice effective barrier contraception during the entire study period and through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse.
14. Written informed consent.
15. Patient is capable of giving informed consent.

Exclusion criteria 20

1. Previous treatment with an PD-1 or PDL-1 blocking agent.
2. Patients who have been using other investigational agents within at least 5 half lives or 4 weeks, whichever is longer, of the most recent agent used prior to start of protocol treatment.
3. Patients who were treated with myelosuppressive chemotherapy or biological therapy within at least 5 half lives or 4 weeks, whichever is longer, before start of protocol treatment.
4. Patients who were treated with steroids for more than 25 mg /day for at least 14 days before start of protocol treatment.
5. Patients receiving radiation therapy within 2 weeks prior to start of protocol treatment. Emergency radiation therapy is allowed, as long as measurable disease (at non-irradiated sites) persists.
6. Prior allogeneic stem cell transplantation or solid organ transplantation.
7. Peripheral neuropathy > grade 2.
8. Active autoimmune diseases or history of autoimmune diseases that may relapse. Note: Patients with the following diseases are not excluded and may proceed to further screening: Controlled Type I diabetes. Hypothyroidism (provided it is managed with hormone replacement therapy only). Controlled celiac disease. Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, alopecia). Any other auto-immune disease that is not expected to recur due to the protocol treatment.
9. Any condition that required systemic treatment with either corticosteroids (> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before study treatment. Note: Patients who are currently or have previously been on any of the following steroid regimens are not excluded: Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent). Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption. Short course (≤ 7 days) of corticosteroid prescribed prophylactically (eg, for contrast dye allergy) or for the treatment of a non-autoimmune condition (eg, delayed-type hypersensitivity reaction caused by contact allergen).
10. History of interstitial lung disease, non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc.
11. Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of progressive multifocal leukoencephalopathy (PML).
12. Patients who have a history of another primary malignancy less than 2 years before study inclusion or previously diagnosed with another malignancy and have evidence of residual disease, with the exception of non-melanoma skin cancer, completely resected melanoma TNMpT1 and carcinoma in situ of the uterine cervix.
13. Patients with any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to first study drug dose.
14. Patients with active HIV (unless viral load undetectable and CD4 counts within the normal range under antiretroviral therapy), active HBV (e.g. HBV DNA PCR positive or HBV surface antigen-positivity), or active HCV (e.g. HCV RNA detected). Patients with inactive HBV are eligible, but antiviral prophylaxis is obligatory.
15. Patients who have any severe and/or uncontrolled cardiovascular condition that could affect their participation in the study such as: Known history of symptomatic congestive heart failure (NYHA III, IV), myocardial infarction ≤ 6 months prior to first study drug. Evidence of current serious uncontrolled cardiac arrhythmia, angina pectoris, electrocardiographic evidence of acute ischemia or active conduction system abnormalities. History of cerebrovascular accident ≤ 6 months before study treatment.
16. Patient who was administered a live vaccine ≤ 4 weeks before study treatment.
17. A history of severe hypersensitivity reactions to chimeric or humanized antibodies or platinum-based compounds.
18. Breast-feeding female patients.
19. Current participation in another clinical trial with medicinal products.
20. Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression free survival probability at 2 years. PFS is defined as time from registration to progression or death from any cause, whichever comes first.

Secondary endpoints 8

1. ORR, mCR and mPR rates (as assessed by FDG-PET/CT) after 2 and 4 cycles of tislelizumab in combination with GP chemotherapy induction.
2. Rate of CTCAE grade 3/4 toxicities of tislelizumab in combination with GP chemotherapy.
3. Rate of CTCAE grade 2 to 4 immune related toxicities of tislelizumab in combination with GP chemotherapy.
4. Rate of CTCAE grade 3/4 toxicities of tislelizumab consolidation treatment.
5. PFS as time-to-event outcome.
6. EFS defined as time from registration to start new HL treatment, progression or death from any cause, whichever comes first.
7. DFS defined as time from start of consolidation therapy to relapse or death from any cause, whichever comes first.
8. OS defined as time from registration to death from any cause.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Sponsor organisation

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Address

Dr. Molewaterplein 40

City

Rotterdam

Postcode

3015 GD

Country

Netherlands

Scientific contact point

Organisation

Haemato Oncology Foundation For Adults Netherlands (HOVON)

Contact name

Dr. S. Tonino

Public contact point

Organisation

Haemato Oncology Foundation For Adults Netherlands (HOVON)

Contact name

HOVON

Third parties 3

Locations

3 EU/EEA countries · 15 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 2 · Art. 52 CTR

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 26 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications