Clinical trial NCT04230330: Nivolumab in Combination With GDP/ L-asparaginase in NK/ T-cell Lymphoma
Official title: A Pilot Study of Nivolumab in Combination With GDP (Gemcitabine, Dexamethasone, Cisplatin)/ L-asparaginase in Patients With Advanced Stage or Relapsed/ Refractory Natural-killer/ T-cell Lymphoma
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: NK/T Cell Lymphoma
Lead sponsor: National Cancer Centre, Singapore
Sponsor class: OTHER
Collaborators: name: Bristol-Myers Squibb
First posted: 2020-01-18
Enrollment: 0
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Number of patients with complete response and partial response to treatment
timeFrame: 6 months after the start of treatment
measure: Number of incidences of grade 3-5 non-haematological adverse events
timeFrame: From start of first treatment to 100 days after last treatment dose
Secondary outcomes:
measure: Progression-free survival
timeFrame: From start of treatment to date of disease progression or death, up to 2.5 years
measure: Overall survival
timeFrame: From the start of treatment to date of death from any cause, up to 2.5 years
measure: Number of patients with complete response and partial response to single agent nivolumab
timeFrame: 6 months after the start of treatment
measure: Number of patients with complete response and partial response to nivolumab in combination with GDP/L-asparaginase
timeFrame: 6 months after the start of treatment
measure: Number of incidences of adverse events
timeFrame: From start of first treatment to 100 days after last treatment dose
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National Cancer Centre Singapore
Study officials:
affiliation: National Cancer Centre, Singapore
name: Tiffany Tang, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.