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

NCT ID: NCT04230330

Last Updated: 2020-11-05

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-12
• Study Completion Date: 2020-06-12

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nivolumab

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.

Group Type: EXPERIMENTAL

IV Nivolumab

Intervention Type: DRUG

240mg every 2 weeks.

Nivolumab + GDP/ L-asparaginase

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.

Group Type: EXPERIMENTAL

IV Nivolumab

Intervention Type: DRUG

Initial treatment dose is 240mg every 2 weeks for 4 doses. Dose changes to 360mg every 3 weeks when given with GDP/L-aspa. Maintenance treatment dose is 240mg every 2 weeks.

IV Gemcitabine

Intervention Type: DRUG

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

IV Cisplatin

Intervention Type: DRUG

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

IV/PO Dexamethasone

Intervention Type: DRUG

10mg on Days 1 to 4 every 21 days

IV L-asparaginase

Intervention Type: DRUG

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

Interventions

IV Nivolumab

240mg every 2 weeks.

Intervention Type: DRUG

IV Nivolumab

Initial treatment dose is 240mg every 2 weeks for 4 doses. Dose changes to 360mg every 3 weeks when given with GDP/L-aspa. Maintenance treatment dose is 240mg every 2 weeks.

Intervention Type: DRUG

IV Gemcitabine

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

Intervention Type: DRUG

IV Cisplatin

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

Intervention Type: DRUG

IV/PO Dexamethasone

10mg on Days 1 to 4 every 21 days

Intervention Type: DRUG

IV L-asparaginase

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

Intervention Type: DRUG

Other Intervention Names

Opdivo; Opdivo

Eligibility Criteria

Inclusion Criteria

• 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
• Platelet count ≥ 75 x10^9/L
• Creatinine clearance ≥ 40ml/min
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN). Higher levels are acceptable if these can be attributed to active haemolysis or ineffective erythropoiesis
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2x ULN
• Women of childbearing potential (WOCBT) must agree to use dual methods of contraception and have a negative serum or urine pregnancy test prior study treatment. Male patients must use an effective barrier method of contraception if sexually active with a WOCBT

Exclusion Criteria

• 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

Inclusion of women and minorities:

Men and women of all ethnic groups are eligible for this study

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

National Cancer Centre, Singapore

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tiffany Tang, MD

Role: PRINCIPAL_INVESTIGATOR

National Cancer Centre, Singapore

Locations

National Cancer Centre Singapore

Singapore, , Singapore

Countries

Singapore

References

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.

Reference Type: BACKGROUND

PMID: 29386072 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28188133 (View on PubMed)

Other Identifiers

CA209-8R6

Identifier Type: -

Identifier Source: org_study_id