Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Genmab | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
The purpose of this study is to measure the efficacy of the study drug, epcoritamab, in participants with relapsed/refractory large B-cell lymphoma.
This is a phase 2 study of outpatient administration of epcoritamab in non-transplant eligible large B-cell lymphoma that has relapsed after, or is refractory to, 1 prior line of therapy.
Phase II clinical trials test the safety and effectiveness of an investigational drug to learn whether the drug works in treating a specific disease. "Investigational" means that the drug is being studied.
The U.S. Food and Drug Administration (FDA) has approved epcoritamab as a treatment option for your disease after at least two prior treatments.
The study treatment may continue for up to 24 cycles or until disease progression, unacceptable toxicity, or withdrawal. Participants will be followed for up to 24 months after last dosage of epcoritamab, or until disease progression or withdrawal, whichever occurs first. After 24 months or at time of progression, participants may be followed annually for survival status.
It is expected that about 30 people will take part in this research study.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Epcoritamab | Experimental | Epcoritamab will be a subcutaneous injection on cycle 1-3 days 1, 8, 15, and 22, cycle 4-9 days 1 and 15, and cycle 10 and onwards day 1. Participants in a complete response will discontinue epcoritamab therapy after 12 cycles. Participants in a partial response or with stable disease at 1 year will continue epcoritamab and will discontinue at 18 or 24 months if in a complete response by those timepoints, otherwise they will continue until progression or intolerance. Dexamethasone (prophylactic corticosteroid) will be given during initial doses of study treatment. Dexamethasone will be taken either once daily or twice daily while receiving epcoritamab. A drug diary will be provided to participants to document information about dexamethasone being taken. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Epcoritamab | Drug | Bispecific IgG1 antibody |
|
| Measure | Description | Time Frame |
|---|---|---|
| 12-month progression free survival (PFS) | The time from registration to the earlier of progression or death due to any cause and will be defined as the percent of patients alive and progression-free at 12 months. Participants alive without disease progression are censored at date of last disease evaluation. | Day 1 until date of first documented disease progression or date of death from any cause, whichever came first, assessed up to 12 months after initial dose of study treatment. |
| Measure | Description | Time Frame |
|---|---|---|
| Complete Response Rate | The proportion of subjects achieving an objective response of complete response (CR) according to the Lugano Classification, prior to start of another non-study anticancer therapy. | Day 1 to 24 months post treatment |
| Overall Response Rate |
Not provided
Inclusion Criteria:
Participants must have large B-cell lymphoma of one of the following histologic subtypes by WHO criteria:
PET measurable disease per Lugano criteria.
Relapsed or refractory disease treated with 1 prior systemic antineoplastic line of therapy that includes an anti-CD20 monoclonal antibody and an anthracycline or an alkylating agent. Patients who have received more than 1 prior systemic antineoplastic line of therapy are not eligible.
Age ≥18 years.
ECOG performance status 0-2.
Not a candidate for high dose chemotherapy and autologous stem cell transplant per the treating investigator, or patient refusal of high dose chemotherapy and autologous transplant.
Participants must meet the following organ and marrow function as defined below:
Participants must have adequate organ function as defined below (unless abnormalities are considered related to target organ involvement or compression by lymphoma):
Ability to remain within 60 minutes of the administration site for 24 hours following cycle 1 day 15 dose of study drug.
The effects of epcoritamab on the developing human fetus are unknown. Women of child-bearing potential must agree to use adequate contraception starting with the first dose of study drug, for the duration of study participation, and for at least 6 months after the last dose of study intervention. Women must also agree not to donate eggs (ova, oocytes) for the purpose of reproduction during this period. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Adequate contraception methods:
Male Partner Sterilization: When the appropriate post-vasectomy documentation of the absence of sperm in the ejaculate.
Use of a combination of any two of the following (one from "a" and one from "b"):
True abstinence, defined as refraining from heterosexual intercourse when this is in line with the preferred and usual lifestyle of the subject.
Nonchildbearing potential is defined as follows:
Women of childbearing potential (WOCBP) must have a negative highly sensitive serum pregnancy test at screening.
Fertile men, defined as all males physiologically capable of conceiving offspring who are sexually active with a female partner of childbearing potential, must agree to use adequate contraception starting with the first dose of study drug, for the duration of study participation, and 3 months after completion of administration. Men must also agree not to donate sperm during this period. Men may agree to remain abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term or persistent basis) OR agree to use a male condom, and their female partner must use an additional highly effective contraceptive method with a failure rate of <1% per year when having sexual intercourse if they are a WOCBP (including pregnant females).
Ability to understand and the willingness to sign a written informed consent document by the participant or a legally authorized representative.
Exclusion Criteria:
Participant must not have used an investigational drug or approved systemic lymphoma therapy within 28 days preceding the first dose of study drug. Steroids for lymphoma disease control are permitted but must be stopped at least 7 days prior to the first dose of study drug.
Participants must not have received prior CD20/CD3 bispecific antibody.
Participants must not have received prior autologous or allogeneic stem cell transplant.
Participants must not have received prior anti-CD19 CAR T-cell therapy.
Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities > Grade 1) with the exception of alopecia. At the discretion of the overall PI, participants with residual toxicities > Grade 1 may be considered eligible if in the opinion of the overall PI the residual toxicity is not likely to interfere with the safety or efficacy assessment of the investigational regimen. For residual hematologic toxicities greater than Grade 1.
Participants must not have known central nervous system involvement by lymphoma.
Participants must not have a current life-threatening illness, medical condition, or organ system dysfunction (other than the disease under study) which, in the Investigator's opinion, could compromise the subject's safety or put the study at risk. Patients that have mild cognitive impairment or dementia are eligible per investigators' opinion.
Participants must not have an uncontrolled active infection. Localized fungal infection of skin or nails are permitted.
Participants must not have active uncontrolled autoimmune disease. Autoimmune disease under control with chronic systemic corticosteroids at a dose of 10 mg/day of prednisone or less, or equivalent corticosteroid, are eligible.
History of allergic reactions attributed to compounds of similar chemical or biologic composition to epcoritamab. A history of an infusion reaction to CD20-directed therapy is not considered an allergic reaction.
Women who are pregnant are excluded from this study because it is unknown if epcoritamab can cause embryo-fetal harm when administered to a pregnant woman. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with epcoritamab, breastfeeding should be discontinued if the mother is treated with epcoritamab on study.
Participant must not have active uncontrolled HIV infection. Participants with HIV are eligible if disease is adequately controlled on an antiretroviral regimen that is in accordance with the current international AIDS Society guidelines, with adequate control defined by presence of both an undetectable viral load, a CD4 count >350, no evidence of AIDS-defining illness (with the exception of a lymphoma diagnosis), and no active opportunistic infections (infections controlled on appropriate anti-infective therapy are permitted).
Participant must not have active hepatitis B infection. Participants with positive HBV core antibody or HBV surface antigen at screening are eligible if HBV viral load is negative by PCR and they are on appropriate antiviral therapy.
Participant must not have active hepatitis C infection. Participants with positive Hepatitis C antibody due to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C RNA test is obtained. Note: Participants with negative Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing.
Subject has no known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. If a subject has signs/symptoms suggestive of SARS-CoV-2 infection or has had recent known exposure to someone with SARS-CoV-2 infection, the subject must have a negative molecular (e.g., PCR) test, or 2 negative antigen test results at least 24 hours apart, to rule out SARS-CoV-2 infection. Note: SARS-CoV-2 diagnostic tests should be applied following local requirements/recommendations. Subjects who do not meet SARS-CoV-2 infection eligibility criteria must be screen failed and may only rescreen after they meet the following SARS-CoV-2 infection viral clearance criteria: No signs/symptoms suggestive of active SARS-CoV-2 infection AND negative testing (molecular (e.g., PCR) result or 2 negative antigen test results at least 24 hours).
Participants must not have received a live virus vaccine within 28 days of first dose of study drug.
Participants must not have any known past or current malignancy other than inclusion diagnosis, except for:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Julie E. Haydu, MD, PhD | Contact | 617-724-4000 | julie_haydu@mgh.harvard.edu |
| Name | Affiliation | Role |
|---|---|---|
| Julie E. Haydu, MD, PhD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Recruiting | Boston | Massachusetts | 02114 | United States |
The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: Julie E. Haydu, MD, PhD (julie_haydu@mgh.harvard.edu) at 617-724-4000. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
Data can be shared no earlier than 1 year following the date of publication
Contact the Partners Innovations team at http://www.partners.org/innovation
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The proportion of subjects achieving an objective response of complete response (CR) or partial response (PR) according to the Lugano Classification, prior to start of another non-study anticancer therapy. |
| Day 1 to 24 months post treatment |
| Median Duration of Response | The time from first response to disease progression or death, and will be summarized using Kaplan-Meier estimates. | Date of first response to first documented disease progression or date of death from any cause, whichever came first, assessed up to 24 months post treatment |
| Median Duration of Complete Response | The time subjects achieve complete response to disease progression or death and will be estimated using Kaplan Meier method or cumulative incidence curves. | Date of complete response to first documented disease progression or date of death from any cause, whichever came first, assessed up to 24 months post treatment |
| Overall Survival | The time from registration to death due to any cause or censored at date last known alive and will be summarized using Kaplan-Meier estimates. | Registration date to date of death from any cause or last known alive date, assessed up to 24 months post treatment |
| Incidence and Severity of Treatment-Emergent Adverse Events | Assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. All participants will be followed and assessed for safety and tolerability of the protocol therapy. | Day 1 to 24 months post treatment |
| Median Time to Resolution of Cytokine Release Syndrome | The duration of time for subjects to resolve cytokine release syndrome (CRS) and will be estimated using Kaplan Meier method or cumulative incidence curves. | Date of cytokine release syndrome to resolution date of cytokine release syndrome |
| Median Time to Resolution of Immune Effector Cell-Associated Neurotoxicity Syndrome | The duration of time for subjects to resolve immune effector cell-associated neurotoxicity syndrome (ICANS) and will be estimated using Kaplan Meier method or cumulative incidence curves. | Date of immune effector cell-associated neurotoxicity syndrome to resolution date of immune effector cell-associated neurotoxicity syndrome |
| Proportion of Subjects Receiving Interventions for CRS and/or ICANS | The number of subjects receiving interventions for CRS and ICANS, CRS, or ICANS and will be estimated using Kaplan Meier method or cumulative incidence curves. | Date of intervention for CRS and/or ICANs to resolution of CRS and/or ICANS |
| Rate of Hospitalization | The frequency of subjects that are hospitalized and will be estimated using Kaplan Meier method or cumulative incidence curves. | Day 1 to 24 months post treatment |
| Rate of Emergency Room Visits | The frequency of subjects that go to the emergency room and will be estimated using Kaplan Meier method or cumulative incidence curves. | Day 1 to 24 months post treatment |
| Newton-Wellesley Hospital | Recruiting | Newton | Massachusetts | 02462 | United States |
|