Nivolumab in Combination With GDP/ L-asparaginase in NK/ T-cell Lymphoma

NCT04230330 | Withdrawn Phase 1

• 1 other identifier: CA209-8R6
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot study investigating the role of nivolumab, a PD-1 inhibitor, in the treatment of advanced stage or relapsed/refractory NKTL. Patients who have received PD-1 inhibitors will be excluded from this study. Patients who have a complete response or good partial response to nivolumab during initial phase will continue to be treated with nivolumab. Patients who have a partial response, stable disease, and progressive disease to nivolumab during initial phase will be treated with the combination of nivolumab and GDP/L-asparaginase.

Conditions

NK/T Cell Lymphoma

Outcome Measures

Primary Outcomes (2)

• Number of patients with complete response and partial response to treatment

  To calculate best overall response rate

  6 months after the start of treatment

• Number of incidences of grade 3-5 non-haematological adverse events

  To calculate the toxicity rate of the treatment

  From start of first treatment to 100 days after last treatment dose

Secondary Outcomes (5)

• Progression-free survival

  From start of treatment to date of disease progression or death, up to 2.5 years

• Overall survival

  From the start of treatment to date of death from any cause, up to 2.5 years

• Number of patients with complete response and partial response to single agent nivolumab

  6 months after the start of treatment

• Number of patients with complete response and partial response to nivolumab in combination with GDP/L-asparaginase

  6 months after the start of treatment

• Number of incidences of adverse events

  From start of first treatment to 100 days after last treatment dose

Study Arms (2)

Nivolumab

EXPERIMENTAL

After 4 doses of nivolumab, if the patient has complete responses (CR) or good partial response (PR), the patient will continue on nivolumab until disease progression, unacceptable toxicities, or discontinuation of treatment. During PET4-directed treatment with single agent nivolumab, if patient has PD, they will proceed to the Nivo+GDP/L-aspa arm.

Drug: IV Nivolumab

Nivolumab + GDP/ L-asparaginase

EXPERIMENTAL

After 4 doses of nivolumab, if the patient has PR, stable disease (SD), or progressive disease (PD), the patient will switch to nivolumab-GDP/L-aspa treatment. After 6 cycles of treatment, if CR is achieved, the patient will continue on single agent nivolumab until disease progression, unacceptable toxicities, or discontinuation of treatment.

Drug: IV Nivolumab; Drug: IV Gemcitabine; Drug: IV Cisplatin; Drug: IV/PO Dexamethasone; Drug: IV L-asparaginase

Interventions

IV Nivolumab DRUG

240mg every 2 weeks.

Also known as: Opdivo

Nivolumab

IV Gemcitabine DRUG

800mg/m2 on Days 1 and 8 every 21 days

Nivolumab + GDP/ L-asparaginase

IV Cisplatin DRUG

20mg/m2 on Day 1 to 4 every 21 days

Nivolumab + GDP/ L-asparaginase

IV/PO Dexamethasone DRUG

10mg on Days 1 to 4 every 21 days

Nivolumab + GDP/ L-asparaginase

IV L-asparaginase DRUG

6000 Units/m2 on Days 2 to 8 every 21 days

Nivolumab + GDP/ L-asparaginase

Eligibility Criteria

• Age: 21 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent
• Subjects must have signed and dated and IRB-approved written consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study
• Target population
• All subjects must have histologically confirmed extranodal natural-killer/T-cell lymphoma (NKTL)
• Subjects must have
• previously untreated stage III or IV NKTL, OR
• relapsed/refractory NKTL who has received at least 2 cycles of one prior regimen or previous radiotherapy administered with curative intent and one of the following:
• Failed to achieve at least a partial response
• Failed to achieve a complete response at the end of planned therapy with curative intent
• Progressed after initial response
• Age ≥ 21 years
• ECOG Performance status 0 - 2
• Subjects must have laboratory test results within these ranges:
• Absolute neutrophil count (ANC) ≥ 1.5 x10\^9/L

You may not qualify if:

• Previous treatment with an anti PD-1, anti PD-L1, anti PD-L2, anti-CD137, or anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
• Previous GDP therapy
• Previous serious hypersensitivity reaction or symptomatic pancreatitis from L-asparaginase
• Uncontrolled central nervous (CNS) disease
• Uncontrolled hepatitis B or C
• Known history of positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• All toxicities attributed to prior anti-cancer therapy other than alopecia and fatigue must have resolved to grade 1 (NCI CTCAE version 4) or baseline before administration of study drug
• Subjects with \> grade 1 peripheral neuropathy
• Any serious or uncontrolled medical disorder, autoimmune disorder or active infection that, in the opinion of the investigator, may increase the risk associated with study participation, study drug administration or would impair the ability fo the subject to receive the study drug
• Subjects who have had prior malignancies (other than NKTL) for ≤5 year with exception of currently treated basal cell, squamous cell carcinoma of the skin or carcinoma "in situ" of the cervix or breast.
• Subjects who have had other anti-cancer therapy including radiation or experimental drug therapy within 28 days of enrollment
• Subjects with known allergies or hypersensitivities to the study drugs
• Prisoners or subjects who are involuntarily incarcerated
• Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious disease) illness
• Pregnant women or women who are breastfeeding are excluded from this study

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

National Cancer Centre Singapore

Singapore, Singapore

Location

Related Publications (2)

• Li X, Cheng Y, Zhang M, Yan J, Li L, Fu X, Zhang X, Chang Y, Sun Z, Yu H, Zhang L, Wang X, Wu J, Li Z, Nan F, Tian L, Li W, Young KH. Activity of pembrolizumab in relapsed/refractory NK/T-cell lymphoma. J Hematol Oncol. 2018 Jan 31;11(1):15. doi: 10.1186/s13045-018-0559-7.

  PMID: 29386072 BACKGROUND

• Kwong YL, Chan TSY, Tan D, Kim SJ, Poon LM, Mow B, Khong PL, Loong F, Au-Yeung R, Iqbal J, Phipps C, Tse E. PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase. Blood. 2017 Apr 27;129(17):2437-2442. doi: 10.1182/blood-2016-12-756841. Epub 2017 Feb 10.

  PMID: 28188133 BACKGROUND

MeSH Terms

Conditions

Lymphoma, Extranodal NK-T-Cell

Interventions

Nivolumab; Gemcitabine; Cisplatin; Asparaginase

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes

Study Officials

• Tiffany Tang, MD

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 13, 2020
• First Posted: January 18, 2020
• Study Start: December 12, 2019
• Primary Completion: June 12, 2020
• Study Completion: June 12, 2020
• Last Updated: November 5, 2020

Record last verified: 2020-11

Locations

SG (1)