Study of Isatuximab and Cemiplimab in Relapsed or Refractory Natural Killer/T-cell Lymphoid Malig… (NCT04763616) | Clinical Trial Compass
CompletedPhase 2
Study of Isatuximab and Cemiplimab in Relapsed or Refractory Natural Killer/T-cell Lymphoid Malignancy
South Korea37 participantsStarted 2021-06-25
Plain-language summary
This study is to analyze the efficacy of PD1 inhibitor and anti-CD38 antibody in relapsed or refractory NK/T-cell lymphoid malignancy. The investigational products of this study are cemiplimab (PD1 inhibitor) and isatuximab (anti-CD38 antibody).
The rationale for the use of cemiplimab in patients with NK/T-cell lymphoid malignancy is the aforementioned PD-L1 expression in tumor cells of ENKTL and ANKL. In addition, the proven efficacy of pembrolizumab in relapsed or refractory ENKTL support the use of PD1 inhibitor as a salvage therapy for this disorder.
The addition of isatuximab to cemiplimab might induce synergistic activity because CD38-mediated immunosuppression as a mechanism of tumor cell escape from PD-1/PD-L1 blockade. Furthermore, targeting CD38 by isatuximab can preferentially block immunosuppressive regulatory T-cells and thereby restore immune effector function against multiple myeloma. These functions of CD38 blocking antibody might help to improve the efficacy of immune checkpoint inhibitor such as PD1 inhibitor.
Given the presence of antibody-mediated cytotoxicity and direct anti-tumor effect of isatuximab against CD38-positive tumor cells, the combination of isatuximab with cemiplimab might show the synergistic activity resulting more improved treatment outcome than PD1 inhibitor alone.
Thus, The investigators designed a phase II study of cemiplimab and isatuximab for patients with relapsed or refractory ENKTL and ANKL. In this study, The investigators analyze the efficacy of this novel combination and their adverse effects.
Who can participate
Age range
19 Years – 85 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Patients should be histologically diagnosed with extranodal NK/T-cell lymphoma or aggressive NK-cell leukemia.
. Patient should be previously treated with at least one type of chemotherapy regimen including autologous stem cell transplantation.
. Patient should have relapsed or refractory disease before enrollment.
. Patient written informed consent obtained prior to any screening procedures.
. Patient should be a male or female ≥ 19 years (Maximum 85 years)
. Patient should have at least one measurable lesion on the CT or PET/CT scan. In case of PET/CT, diagnostic quality CT part of PET/CT is needed to define measurability. Cf. If a patient only has non-measurable lesion on the CT or PET/CT scan (e.g. bone marrow involvement, malignant effusion, and hemophagocytic lymphohistiocytosis), its association with disease progression or relapse should be determined by an investigator. Based on investigators' decision, patients with non-measurable lesion could be enrolled.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1This trial combined isatuximab and cemiplimab specifically for relapsed or refractory NK/T-cell lymphoma — since it's a Phase 2 study, what do we actually know so far about how safe and effective this combination appeared to be, and has any data been published yet?
2The trial measured complete response rate as its main goal — based on the results, how does the complete response rate from this combination compare to other options available to me at this stage of my disease?
3Since this trial is now completed and no longer enrolling, is there any way I could still access isatuximab or cemiplimab — either through another open trial, a compassionate use program, or an off-label prescription?
4NK/T-cell lymphoma that has relapsed or become refractory is very hard to treat — given where I am in my treatment history, would you consider this combination a realistic next step for me, or are there standard salvage therapies I should try first?
5Cemiplimab is a checkpoint inhibitor, which can cause immune-related side effects — given my specific health history, are there any reasons you'd be concerned about me receiving this type of immunotherapy?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Complete response rate
Timeframe: 3 years after completion of the clinical trial drug administration of the last subject
. Patient should have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 which is not declining during the last 2 weeks before the signature of the main study Informed Consent Form (S-ICF).
. Patient should have adequate bone marrow function as defined by the following laboratory values: Absolute Neutrophil Count (ANC) ≥ 1.0 x 109/L; Platelets ≥ 50 x 109/L; Hemoglobin ≥ 8.0 g/dL Cf. If the cause of cytopenia is related with bone marrow involvement of tumor cells, a patient could be enrolled after blood transfusion or G-CSF support by investigator's decision.
Exclusion criteria
. Patient has history of or known carcinomatous meningitis, or evidence of symptomatic leptomeningeal disease or secondary CNS involvement on CT or MRI scan.
. Patient has a concurrent malignancy or has had a malignancy in the last 3 years prior to start of study treatment (with the exception of adequately treated basal or squamous cell carcinoma or cervical carcinoma in situ)
. Patient has had major surgery within 21 days prior to starting study drug or has not recovered from major side effects of the surgery
. Patient with current use of immunosuppressive medication, EXCEPT for the following: - Intranasal, inhaled, topical steroids, or local steroid injection (e.g., intra-articular injection) - Systemic corticosteroids at physiologic doses ≤ 10 mg/day of prednisone or equivalent - Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication). The use of 10 mg or more of prednisolone may be acceptable for adrenal insufficiency according to the investigator's judgment.
. Patient has clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (\< 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (≥ New York Heart Association Classification Class II), or serious cardiac arrhythmia requiring medication including any of the following: - Left Ventricular Ejection Fraction (LVEF) \< 50% as determined by echocardiogram - QTc \> 480 msec on screening ECG (using the QTcF formula) - Unstable angina pectoris - Ventricular arrhythmias except for benign premature ventricular contractions - Supraventricular and nodal arrhythmias not controlled with medication - Conduction abnormality requiring a pacemaker - Valvular disease with documented compromise in cardiac function
. Patient has known history of testing positive for HIV or known acquired immunodeficiency syndrome
. Patient has known prior severe hypersensitivity to investigational product or any component in its formulations, including known severe hypersensitivity reactions to monoclonal antibodies (NCI CTCAE v.5.0 Grade ≥ 3).
. Patient has other concurrent severe and/or uncontrolled medical condition that would, in the investigator's judgment contraindicate her participation in the clinical study (e.g. uncontrolled diabetes, chronic pancreatitis, active chronic hepatitis etc.). Other severe acute or chronic medical conditions include colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis or psychiatric conditions including recent (within the past year) or active suicidal ideation or behavior; or laboratory abnormalities that may increase the risk associated with study participation or study treatment administration or may interfere with the interpretation of study results and, in the judgment of the investigator. Cf. "Persisting toxicity related to prior therapy (NCI CTCAE v.5.0 Grade \> 1); however, alopecia, sensory neuropathy Grade ≤ 2, or other Grade ≤ 2 not constituting a safety risk based on investigator's judgment are acceptable."