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

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ClinicalTrials.gov Identifier: NCT04230330
Recruitment Status : Withdrawn (PI has left the institution.)
First Posted : January 18, 2020
Last Update Posted : November 5, 2020
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
National Cancer Centre, Singapore

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.


Condition or disease Intervention/treatment Phase
NK/T Cell Lymphoma Drug: IV Nivolumab Drug: IV Gemcitabine Drug: IV Cisplatin Drug: IV/PO Dexamethasone Drug: IV L-asparaginase Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 12, 2019
Actual Primary Completion Date : June 12, 2020
Actual Study Completion Date : June 12, 2020


Arm Intervention/treatment
Experimental: 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.
Drug: IV Nivolumab
240mg every 2 weeks.
Other Name: Opdivo

Experimental: 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.
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.
Other Name: Opdivo

Drug: IV Gemcitabine
800mg/m2 on Days 1 and 8 every 21 days

Drug: IV Cisplatin
20mg/m2 on Day 1 to 4 every 21 days

Drug: IV/PO Dexamethasone
10mg on Days 1 to 4 every 21 days

Drug: IV L-asparaginase
6000 Units/m2 on Days 2 to 8 every 21 days




Primary Outcome Measures :
  1. Number of patients with complete response and partial response to treatment [ Time Frame: 6 months after the start of treatment ]
    To calculate best overall response rate

  2. Number of incidences of grade 3-5 non-haematological adverse events [ Time Frame: From start of first treatment to 100 days after last treatment dose ]
    To calculate the toxicity rate of the treatment


Secondary Outcome Measures :
  1. Progression-free survival [ Time Frame: From start of treatment to date of disease progression or death, up to 2.5 years ]
  2. Overall survival [ Time Frame: From the start of treatment to date of death from any cause, up to 2.5 years ]
  3. Number of patients with complete response and partial response to single agent nivolumab [ Time Frame: 6 months after the start of treatment ]
    To calculate the overall response rate of single agent nivolumab

  4. Number of patients with complete response and partial response to nivolumab in combination with GDP/L-asparaginase [ Time Frame: 6 months after the start of treatment ]
  5. Number of incidences of adverse events [ Time Frame: From start of first treatment to 100 days after last treatment dose ]
    To calculate the rate of adverse events from nivolumab with or without GDP/L-asparaginase



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04230330


Locations
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Singapore
National Cancer Centre Singapore
Singapore, Singapore
Sponsors and Collaborators
National Cancer Centre, Singapore
Bristol-Myers Squibb
Investigators
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Principal Investigator: Tiffany Tang, MD National Cancer Centre, Singapore
Publications:
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Responsible Party: National Cancer Centre, Singapore
ClinicalTrials.gov Identifier: NCT04230330    
Other Study ID Numbers: CA209-8R6
First Posted: January 18, 2020    Key Record Dates
Last Update Posted: November 5, 2020
Last Verified: November 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, T-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Gemcitabine
Dexamethasone
Nivolumab
Asparaginase
Antineoplastic Agents
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors