Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 2024-514440-86-00 | EU Trial (CTIS) Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| AbbVie | INDUSTRY |
| Incyte Corporation | INDUSTRY |
| Evidenze CRO | OTHER |
Not provided
Not provided
Not provided
Not provided
phase II, response-adaptive, open-label, multicenter study aiming to include 80 patients in 78 months. Patients will receive 3 cycles of epcoritamab monotherapy and, since cycle 4, they can continue with epcoritamab monotherapy until cycle 12 or change to combination therapy (epcoritamab + tafasitamab + lenalidomide) until cycle 15. Patients will be followed up to 5 years.
Epcoritamab is a full-length bispecific IgG1 antibody directed against two proteins, CD3 on the T lymphocyte and CD20 on the lymphoma cell. This antibody redirects and activates T cells, generating an immune synapse that eventually eliminates malignant cells expressing CD20.
Previous studies have demonstrated that Epcoritamab has potent antitumor activity as a monotherapy agent, with a favorable and manageable safety profile.
Since its efficacy is so favorable it is reasonable to think that it could be an excellent option for first-relapse patients. However, to date, there is no data on this therapy's usefulness as second-line treatment. Therefore we intend to evaluate the efficacy of Epcoritamab as a treatment option for patients with first-relapse LBCL.
The purpose of this study is to determine the efficacy of Epcoritamab as second line treatment for LBCL patients. On the basis of the clinical experience, it is hypothesized that Epcoritamab would provide a better complete response rate (CRR) in comparison to Platinum-based immunochemotherapy (CRR=25%), Polatuzumab-Bendamustin Rituximab (CRR=40%) and Tafasitamab-Lenalidomide (CRR=43%).
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| EPCO monotherapy | Experimental | Epcoritamab in monotherapy will be administred until cycle 12. |
|
| Combination therapy | Experimental | 3 cycles of Epcoritamab in monotherapy will be administred and then Epcoritamab will be administred with Tafasitamab and Lenalidomide from cycle 4 until cycle 15. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Epcoritamab | Drug | Patients will receive 12 cycles of Epcoritamab monotherapy. |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of Epcoritamab monotherapy | The efficacy of Epcoritamab monotherapy will be centrally evaluated by the best CRR at any moment since initiation. The CRR will be assessed by PET-CT according to Lugano Classification and is defined as the proportion of patients who achieve a best response of complete response (CR) at any moment since initiation of Epcoritamab first administration. | Cycle 3, cycle 4, cycle 7, cycle 10, cycle 13 (for combination therapy) and EoT (28 days after last administration of investigational product) visits. Each cycle is 28 days. |
| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of Epcoritamab monotherapy after 3 cycles | The efficacy of Epcoritamab monotherapy will be centrally evaluated by the best CRR, defined as the proportion of patients who achieve a best response of CR after 3 cycles of Epcoritamab administration. | At the end of cycle 3 (each cycle is 28 days) |
| Efficacy of Epcoritamab monotherapy and combination therapy by CRR |
| Measure | Description | Time Frame |
|---|---|---|
| Response of patients stopping treatment by PFS | To compare the PFS of patients stopping therapy after 1 year of treatment (CR by PET-CT and negative MRD) with the groups of patients who continue monotherapy or receive combination. | At EoT visit (28 days after last administration of Study drug) for monotherapy and at C13 visit for combination therapy (each cycle is 28 days). |
Inclusion Criteria:
Written informed consent must be obtained before any study-specific assessment is performed.
Age >18 years
Patients with Relapse/Refractory histologically confirmed LBCL, including, Diffuse Large B Cell Lymphoma (DLBCL); Primary Mediastinal Large B Cell Lymphoma (PMBCL), High-grade B-cell lymphoma (HGBCL); and grade 3B Follicular Lymphoma.
Relapsed disease is defined as complete remission to first line therapy followed by a recurrence of the disease after a minimum of 6 months of completion of first-line therapy. A biopsy at the time of relapse is recommended but not mandatory.
Refractory disease is defined as no objective response to first line therapy (biopsy not mandatory if diagnostic sample available). Four groups of patients are eligible:
Patients must have received adequate first-line therapy including at a minimum: an anti-CD20 monoclonal antibody (rituximab or obinutuzumab), and CHOP (cyclophosphamide, hydroxydaunomycin, oncovin, and prednisone) or CHOP-like chemotherapy.
At the investigator's discretion, the patient should not be a candidate for 1st relapse CAR-T therapy or unwilling to receive CAR-T therapy.
Patients must be autologous stem cell transplantation (ASCT)-ineligible: Age ≥65 and/or HTC-CI ≥3 or or unwilling to receive transplant.
PET positive disease.
Performance status according to Eastern Cooperative Oncology Group (ECOG) 0 to 2.
Patients meeting with the following hematology values:
Female patients of child-bearing potential must have a negative urine or serum pregnancy test at screening and agree to use highly effective methods of contraception (e.g., established use of oral, injected or implanted combined (estradiol and progesterone containing) hormonal contraception; placement of an intrauterine device (IUD) or intrauterine system (IUS) upon enrollment according to the recommendations provided by Clinical Trial Facilitation Group (CTFG), during the treatment period and for 4 months after the last dose of study medication. Moreover, the patient must agree to ongoing pregnancy testing during the course of the study, and after study therapy has ended. This applies even if the patient practices complete and continued sexual abstinence.
Women not of childbearing potential are defined as: premenarchal; postmenopausal (greater than 50 years of age with amenorrhea for at least 12 months or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone (FSH) level greater than 40 IU per L or milli-International unit (mIU) per mL); permanently sterilized (e.g., bilateral tubal occlusion [which includes tubal ligation procedures as consistent with local regulations], hysterectomy, bilateral salpingectomy, bilateral oophorectomy); or otherwise be incapable of pregnancy.
Male patients must use a reliable method of contraception (if sexually active with a female of child-bearing potential) upon enrollment according to the recommendations provided by CTFG, during the treatment period, and for 4 months following the last dose of investigational drug or agreement to remain abstinent. Agreement to refrain from donating blood or sperm during the study participation and for 4 months after the last dose of study medication.
Women must agree not to donate blood or oocytes during the course of the study and for 4 months after the last dose of study medication. Restrictions concerning blood donation apply as well to females who are not of childbearing potential. Men must also not donate sperm during the trial and for 4 months after receiving the last dose of study drug.
Females of childbearing potential must refrain from breastfeeding during the course of the study and for 4 months after the last dose of study medication.
Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.
Not included in other clinical trial or treated with an experimental drug.
Exclusion Criteria:
Patients who received more than one prior line of systemic therapy
Patients with detectable Central Nervous System (CNS) lymphoma
Significant organ function impairment:
Serious accompanying disorder leading to impaired organ function causing significant clinical problems and reduced life expectancy of less than 3 months.
Have a history of deep venous thrombosis/embolism, threatening thromboembolism or known thrombophilia or are at a high risk for a thromboembolic event in the opinion of the investigator and who are not willing/able to take venous thromboembolic event prophylaxis during the entire treatment period
Known clinically significant cardiac disease, including:
Known past or current malignancy other than inclusion diagnosis, except for: Cervical carcinoma of Stage 1B or less; Non-invasive basal cell or squamous cell skin carcinoma; Non-invasive, superficial bladder cancer; Localized low grade prostate cancer (up to Gleason score 6); DCIS of the breast; Other malignancy that has been treated with curative intent and has remained in remission for 3 years.
Previous ASCT.
Prior anti-CD3 and CD20 bispecific antibodies therapy or prior treatment with tafasitamab.
Presence of severe infection that is uncontrolled or requiring IV antimicrobials for management.
History of HIV infection or acute or chronic active hepatitis B or C infection.
Females who are pregnant or breastfeeding.
Richter's transformation or prior chronic lymphocytic leukemia (CLL).
Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 4 weeks prior to Cycle 1 Day 1.
Recent major surgery (within 4 weeks before the start of Cycle 1 Day 1) other than for diagnosis.
Vaccination with a live vaccine or COVID-19 vaccination within 4 weeks prior to treatment.
History of hypersensitivity to any of the study drugs or their ingredients or to drugs with similar structure. History of severe allergic or anaphylactic reactions to human, humanized, chimeric, or murine monoclonal antibodies.
Close affiliation with the investigator (e.g. a close relative) or persons working at the study site.
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Auxi Moreno | Contact | +34 683 636 850 | amoreno@geltamo.com | |
| Ana María Méndez | Contact | +34 942 203 450 | administracion@geltamo.com |
| Name | Affiliation | Role |
|---|---|---|
| Mariana Bastos-Oreiro | Hospital General Universitario Gregorio Marañón | Principal Investigator |
| Pau Abrisqueta | Hospital Universitari Vall d'Hebrón | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Universitario Miguel Servet | Not yet recruiting | Zaragoza | Aragon | 50009 | Spain |
Not provided
| Label | URL |
|---|---|
| GELTAMO web page | View source |
Not provided
Data obtained through this study may be provided to qualified researchers with academic interest in hematology diseases. All individual data collected during the trial will be available. Data shared will be coded, with no PHI included. Study protocol, statistical analysis plan, informed consent form and clinical study report will be also available. Information will be available beginning 6 months after final publication with no end date established. Approval of the request and execution of all applicable agreements are prerequisites to the sharing of data with the requesting party. Data requests can be submitted starting 6 months after article publication. Access to trial IPD can be requested by qualified researchers and will be provided following review and approval of a research and execution of a Data Sharing Agreement (DSA). For more information or to submit a request, please contact to GELTAMO though the web page: https://www.geltamo.com/contacto
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Epcoritamab, tafasitamab and lenalidomide |
| Drug |
Patients will receive 3 cycles of Epcoritamab monotherapy and then 12 cycles of Epcoritamab, Tafasitamab and Lenalidomide. |
|
The efficacy of Epcoritamab monotherapy and combination therapy with tafasitamab-lenalidomide will be evaluated by local investigators and central evaluation as per CRR (locally evaluated for Epcoritamab monotherapy; local and central evaluation for combination therapy). |
| Cycle 3, cycle 4, cycle 7, cycle 10, cycle 13 (for combination therapy) and EoT (28 days after last administration of investigational product) visits. Each cycle is 28 days. |
| Evaluation of MRD | The efficacy of Epcoritamab monotherapy and combination therapy will be evaluated by MRD (positive or negative) from ctDNA samples immediately before initiation of C3, C4, C7, C10, C12, C13, C15, End of Treatment (EoT) and cycles 18/24 (epcoritamab monotherapy) or cycles 21/27 (combination therapy). | Cycles 3, 4, 7, 10, 12, 13, 15 (each cycle is 28 days), EoT (28 days after last administration of Study drug) and cycles 18 and 24 (epcoritamab monotherapy) or cycles 21 and 27 (combination therapy) visits (each cycle is 28 days). |
| Evaluation of patients with negative MRD by PFS | The PFS of patients with negative MRD at Visit 3 (V3) (immediately before administrating C3 of Epcoritamab monotherapy). | At cycle 3 visit (each cycle is 28 days). |
| Safety and tolerability | The safety and tolerability of Epcoritamab monotherapy and combination therapy are evaluated as follows:
| Baseline, during all the cycles day 1 visit (each cycle is 28 days) and at EoT (28 days afert las administration of Study drug). |
| Efficacy of Epcoritamab Monotherapy and Combination therapy by ORR | The efficacy of Epcoritamab monotherapy and combination therapy with tafasitamab-lenalidomide will be evaluated by local investigators and central evaluation as per ORR at any time. | Cycle 3, cycle 4, cycle 7, cycle 10, cycle 13 (for combination therapy) and EoT (28 days after last administration of investigational product) visits. Each cycle is 28 days |
| Efficacy of Epcoritamab Monotherapy and combination therapy by DoR | The efficacy of Epcoritamab monotherapy and combination therapy with tafasitamab-lenalidomide will be evaluated by local investigators and central evaluation as per DoR at any time. | Cycle 3, cycle 4, cycle 7, cycle 10, cycle 13 (for combination therapy) and EoT (28 days after last administration of investigational product) visits. Each cycle is 28 days |
| Efficacy of Epcoritamab monotherapy and combination therapy by DoCR | The efficacy of Epcoritamab monotherapy and combination therapy with tafasitamab-lenalidomide will be evaluated by local investigators and central evaluation as per DoCR at any time. | Cycle 3, cycle 4, cycle 7, cycle 10, cycle 13 (for combination therapy) and EoT (28 days after last administration of investigational product) visits. Each cycle is 28 days |
| Efficacy of Epcoritamab monotherapy and combination therapy by EFS | The efficacy of Epcoritamab monotherapy and combination therapy with tafasitamab-lenalidomide will be evaluated by local investigators and central evaluation as per Event-free survival (EFS) at any time. | Cycle 3, cycle 4, cycle 7, cycle 10, cycle 13 (for combination therapy) and EoT (28 days after last administration of investigational product) visits. Each cycle is 28 days |
| Efficacy of Epcoritamab monotherapy and combination therapy by PFS | The efficacy of Epcoritamab monotherapy and combination therapy with tafasitamab-lenalidomide will be evaluated by local investigators and central evaluation as per PFS at any time. | Cycle 3, cycle 4, cycle 7, cycle 10, cycle 13 (for combination therapy) and EoT (28 days after last administration of investigational product) visits. Each cycle is 28 days |
| Efficacy of Epcoritamab montherapy and combination therapy by OS | The efficacy of Epcoritamab monotherapy and combination therapy with tafasitamab-lenalidomide will be evaluated by local investigators and central evaluation as per OS at any time. | Cycle 3, cycle 4, cycle 7, cycle 10, cycle 13 (for combination therapy) and EoT (28 days after last administration of investigational product) visits. Each cycle is 28 days |
| Evaluation of patients with negative MRD by OS | The OS of patients with negative MRD at Visit 3 (V3) (immediately before administrating C3 of Epcoritamab monotherapy). | At cycle 3 visit (each cycle is 28 days). |
| Evaluation of patients with negative MRD by DoR | The DoR of patients with negative MRD at Visit 3 (V3) (immediately before administrating C3 of Epcoritamab monotherapy). | At cycle 3 visit (each cycle is 28 days). |
| Correlation between biomarkers and study treatment by ORR | Correlation between biomarkers and study treatment efficacy determined by ORR. | Cycles 3, 4, 7, 10, 12, 13, 15 (each cycle is 28 days), EoT (28 days after last administration of Study drug) and cycles 18 and 24 (epcoritamab monotherapy) or cycles 21 and 27 (combination therapy) visits (each cycle is 28 days). |
| Efficacy of Epcoritamab monotherapy and combination therapy in patients reintroducing treatment by DoR | Efficacy of Epcoritamab or Epcoritamab/Tafasitamab by DoR in patients reintroducing the study treatment with a MRD positive result. | After reintroduction of study treatment due to MRD positive result, on cycles 13, 16, 19, 22, 25, 28 visits (each cycle is 28 days). |
| MRD negativity | Median duration of molecular response (MRD negativity). | through study completion, an average of 5 years |
| Correlation between tumor volume and efficacy | Correlation between Total Metabolic Tumor Volume (centrally evaluated) and study treatment efficacy determined by PFS and OS. | Cycle 3, cycle 4, cycle 7, cycle 10, cycle 13 (for combination therapy) and EoT (28 days after last administration of investigational product) visits. Each cycle is 28 days. |
| ctDNA levels | Descriptive analysis of dynamic changes in ctDNA levels | Cycles 3, 4, 7, 10, 12, 13, 15 (each cycle is 28 days), EoT (28 days after last administration of Study drug) and cycles 18 and 24 (epcoritamab monotherapy) or cycles 21 and 27 (combination therapy) visits (each cycle is 28 days). |
| Correlation between lymphocyte subsets and efficacy | Correlation between lymphocyte subsets and study treatment efficacy determined by ORR, CRR, DoR, PFS and OS and safety determined by type, frequency, and severity of adverse events. | Through study completion, an average of 5 years. |
| Response of patients stopping treatment | To compare the DoR of patients stopping therapy after 1 year of treatment (CR by PET-CT and negative MRD) with the groups of patients who continue monotherapy or receive combination. | At EoT visit (28 days after last administration of Study drug) for monotherapy and at C13 visit for combination therapy (each cycle is 28 days). |
| Correlation between biomarkers and study treatment efficacy by CRR | Correlation between biomarkers and study treatment efficacy determined by CRR. | Cycles 3, 4, 7, 10, 12, 13, 15 (each cycle is 28 days), EoT (28 days after last administration of Study drug) and cycles 18 and 24 (epcoritamab monotherapy) or cycles 21 and 27 (combination therapy) visits (each cycle is 28 days). |
| Correlation between biomarkers and study treatment efficacy DoR | Correlation between biomarkers and study treatment efficacy determined by DoR, PFS and OS. | Cycles 3, 4, 7, 10, 12, 13, 15 (each cycle is 28 days), EoT (28 days after last administration of Study drug) and cycles 18 and 24 (epcoritamab monotherapy) or cycles 21 and 27 (combination therapy) visits (each cycle is 28 days). |
| Correlation between biomarkers and study treatment efficacy by PFS | Correlation between biomarkers and study treatment efficacy determined by PFS. | Cycles 3, 4, 7, 10, 12, 13, 15 (each cycle is 28 days), EoT (28 days after last administration of Study drug) and cycles 18 and 24 (epcoritamab monotherapy) or cycles 21 and 27 (combination therapy) visits (each cycle is 28 days). |
| Correlation between biomarkers and study treatment efficacy by OS | Correlation between biomarkers and study treatment efficacy determined by OS. | Cycles 3, 4, 7, 10, 12, 13, 15 (each cycle is 28 days), EoT (28 days after last administration of Study drug) and cycles 18 and 24 (epcoritamab monotherapy) or cycles 21 and 27 (combination therapy) visits (each cycle is 28 days). |
| Efficacy of Epcoritamab monotherapy and combination therapy in patients reintroducing treatment by PFS | Efficacy of Epcoritamab or Epcoritamab/Tafasitamab by PFS in patients reintroducing the study treatment with a MRD positive result. | After reintroduction of study treatment due to MRD positive result, on cycles 13, 16, 19, 22, 25, 28 visits (each cycle is 28 days) |
| Efficacy of Epcoritamab monotherapy and combination therapy in patients reintroducing treatment by OS | Efficacy of Epcoritamab or Epcoritamab/Tafasitamab by OS in patients reintroducing the study treatment with a MRD positive result. | After reintroduction of study treatment due to MRD positive result, on cycles 13, 16, 19, 22, 25, 28 visits (each cycle is 28 days) |
| Hospital Universitario de Burgos | Not yet recruiting | Burgos | Castille and León | 09006 | Spain |
|
| ICO Badalona | Not yet recruiting | Badalona | Catalonia | 08916 | Spain |
|
| Hospital Universitari Vall d'Hebrón | Not yet recruiting | Barcelona | Catalonia | 08035 | Spain |
|
| Hospital San Pedro de Alcántara | Not yet recruiting | Cáceres | Extremadura | 10003 | Spain |
|
| Hospital General Universitario Gregorio Marañón | Recruiting | Madrid | Madrid | 28007 | Spain |
|
| Hospital Universitario Infanta Leonor | Not yet recruiting | Madrid | Madrid | 28031 | Spain |
|
| Hospital Universitario Fundación Jiménez Díaz | Not yet recruiting | Madrid | Madrid | 28040 | Spain |
|
| Hospital Virgen de la Arrixaca | Not yet recruiting | El Palmar | Murcia | 30120 | Spain |
|
| Hospital Universitario Costa del Sol | Not yet recruiting | Marbella | Málaga | 29603 | Spain |
|
| Hospital Universitario Central de Asturias | Not yet recruiting | Oviedo | Principality of Asturias | 33011 | Spain |
|
| Hospital Universitario de Canarias | Not yet recruiting | San Cristóbal de La Laguna | Tenerife | 38320 | Spain |
|
| Hospital Universitario Dr. Peset | Not yet recruiting | Valencia | Valencia | 46017 | Spain |
|
| Hospital Universitario y Politécnico La Fe | Not yet recruiting | Valencia | Valencia | 46024 | Spain |
|
| Hospital Universitario de Basurto | Not yet recruiting | Bilbao | Vizcaya | 48013 | Spain |
|
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D016403 | Lymphoma, Large B-Cell, Diffuse |
| D012008 | Recurrence |
| ID | Term |
|---|---|
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
| D016393 | Lymphoma, B-Cell |
| D008228 | Lymphoma, Non-Hodgkin |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C000613469 | tafasitamab |
| D000077269 | Lenalidomide |
| ID | Term |
|---|---|
| D010797 | Phthalimides |
| D010795 | Phthalic Acids |
| D000146 | Acids, Carbocyclic |
| D002264 | Carboxylic Acids |
| D009930 | Organic Chemicals |
| D010881 | Piperidones |
| D010880 | Piperidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D054833 | Isoindoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
Not provided
Not provided