Trial Title:
Safety and Efficacy of Epcoritamab With Gemcitabine, Dexamethasone, and Cisplatin (GDP) Salvage Chemotherapy in Relapsed Refractory Large B-cell Lymphoma
NCT ID:
NCT05852717
Condition:
Large Cell Lymphoma, Diffuse
Relapsed Cancer
Refractory Cancer
Conditions: Official terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Large B-Cell, Diffuse
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
AutoSCT OR CAR T-cell Therapy
Description:
Autologous stem cell transplant (AutoSCT) or CAR T-cell therapy will be performed after
Cycle 3 of receiving epcoritamab and GDP
Arm group label:
GDP + Epcoritamab + AutoSCT or CAR T-cell therapy
Other name:
Autologous transplant
Other name:
chimeric antigen receptor (CAR) T-cell
Intervention type:
Drug
Intervention name:
GDP
Description:
Gemcitabine Cisplatin Dexamethasone
Arm group label:
GDP + Epcoritamab + AutoSCT or CAR T-cell therapy
Arm group label:
GDP + Epcoritamab + Epcoritamab Maintenance
Intervention type:
Drug
Intervention name:
Epcoritamab
Description:
Epcoritamab
Arm group label:
GDP + Epcoritamab + AutoSCT or CAR T-cell therapy
Arm group label:
GDP + Epcoritamab + Epcoritamab Maintenance
Summary:
Subjects with relapsed large cell lymphoma will receive 3 cycles of combination therapy
consisting of GDP and epcoritamab. Each cycle will last 21 days. GDP consists of
gemcitabine 1000 mg/m2 IV on Days 1 and 8, cisplatin 75 mg/m2 IV on Day 1, and
dexamethasone 40 mg orally on Days 1 through 4. Epcoritamab will be administered
subcutaneously (SC) on Days 1, 8, and 15. Patients will receive granulocyte colony
stimulating factor (G-CSF) between Day 8 through Day 10 of each cycle of combination
therapy.
Patients will then undergo radiology imaging for disease assessment. Patients may proceed
to SCT(autologous or allogeneic) or CAR T-cell therapy or epcoritamab monotherapy upon
completion of Cycle 3 per investigator discretion. The rationale for subjects not
proceeding to autoSCT or CAR T-cell therapy will be captured in the eCRFs.
Patients who do not undergo SCT or CAR T-cell therapy may have the option to receive
study treatment with epcoritamab monotherapy following completion of Cycle 3. Epcoritamab
monotherapy will be offered to selected subjects who become ineligible to undergo SCT or
CAR T-cell therapy (such as social situation, change in subject decision). The decision
to offer epcoritamab monotherapy will be per investigator's discretion. However, subjects
must have demonstrated a response to the combination therapy (partial remission or
complete remission) per disease assessment scans prior to offering epcoritamab
monotherapy. Epcoritamab monotherapy should begin 2 weeks following Cycle 3 Day 15.
Monotherapy will consist of epcoritamab 48 mg administered subcutaneously on Days 1 and
15 of each 28 day cycle for Cycle 4 to Cycle 9 or until unacceptable toxicity, or disease
progression per the Lugano Criteria.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Written informed consent and HIPAA authorization for release of personal health
information prior to registration. NOTE: HIPAA authorization may be included in the
informed consent or obtained separately.
2. Age ≥ 18 years at the time of consent.
3. ECOG Performance Status of 0-2 within 28 days prior to registration.
4. Histological confirmed CD20+ relapsed large cell lymphoma according to the 5th
edition of the WHO classification of the hematolymphoid tumors and the 2022
international consensus classification of mature lymphoid neoplasms including
de-novo and transformed from prior indolent B-cell NHL such as follicular lymphoma,
or marginal zone lymphoma (33, 34). NOTE: Subjects with high-grade B-cell lymphoma
(HGBCL), NOS subtype, and high-grade B-cell lymphoma with c-MYC, Bcl2 and/or Bcl6
rearrangements (double or triple hit lymphoma) are eligible. Patients with primary
mediastinal B-cell lymphoma, and T-cell histiocyte-rich B-cell lymphoma, primary
cutaneous diffuse large B-cell lymphoma, leg type, Intravascular large B-cell
lymphoma, Epstein-Barr virus-positive diffuse large B-cell lymphoma, NOS, Diffuse
large B-cell lymphoma associated with chronic inflammation, and ALK-positive large
B-cell lymphoma are eligible. Patients with Burkitt lymphoma or lymphoplasmacytic
lymphoma are not eligible.
5. Positron emission tomography (PET) positive measurable disease with at least 1 node
having the longest diameter (LDi) greater than (>) 1.5 centimeter (cm) or 1
extranodal lesion with LDi >1 cm (per the Lugano Criteria 2014).
6. Have received at least 1 prior line of systemic therapy for the treatment of large
cell lymphoma. NOTE: Prior radiation therapy or systemic corticosteroids will not be
considered a line of therapy.
7. Must have had relapsed or refractory disease following standard frontline
chemotherapy. Refractory disease is defined as large cell lymphoma not achieving
complete remission, progressing or relapsing within 6 months after first-line
chemotherapy based on PET/CT per the Lugano criteria. Relapsed disease is defined as
disease that recurs beyond 6 months after completion of initial chemotherapy based
on PET/CT per the Lugano criteria.
8. Patients must be deemed eligible to proceed with stem cell transplantation
(autologous or allogeneic) or CAR T-cell therapy per treating physician discretion.
Patients being considered for allogeneic stem cell transplant may be eligible.
9. Archival tissue obtained within 2 years of signing consent is required if available
and will be identified at screening and shipped prior to Cycle 2 Day 1. If archival
tissue is not available, fresh tissue from a standard of care biopsy is required. If
a subject does not have archival tissue or is not undergoing a standard of care
biopsy, they are not eligible for the trial. NOTE: A pre-treatment fresh tissue core
or excisional biopsy at screening is preferred which should be considered standard
of care.
10. Demonstrate adequate organ function. All screening labs to be obtained within 21
days prior to registration. *Patients with bone marrow involvement will be eligible
to participate in the study but must meet hematologic parameters.
11. Life expectancy of ≥ 6 months, as determined by the enrolling physician or protocol
designee.
12. Females subjects of childbearing potential must have a negative urine or serum
pregnancy test within 24 hours prior to study treatment. If a urine test is done and
it is positice ir cannot be confirmed as negative, a serum pregnancy test will be
required.
13. Female subjects of childbearing potential and male subjects must be willing to
abstain from penile-vaginal intercourse or to use an effective method(s) of
contraception.
14. As determined by the enrolling physician or protocol designee, ability of the
subject to understand and comply with study procedures for the entire length of the
study.
Exclusion Criteria:
1. Previous treatment with gemcitabine, cisplatin, and epcoritamab or other bispecific
T-cell engager antibody (BiTE) such aas glofitamab, mosunetuzumab, or odronextamab.
2. Known active central nervous system or meningeal involvement by large cell lymphoma
at time of screening. Patients diagnosed with CNS disease who achieved and
maintained CNS CR at the time of relapse are eligible. Lumbar puncture must be done
in this case prior to study entry to demonstrate CNS CR status. Tests to investigate
CNS involvement are required otherwise only if clinically indicated (i.e. disease
suspected on basis of symptoms or other findings).
3. Contraindication to any drug contained in the combination therapy regimen (GDP).
4. Known hypersensitivity or allergic reaction to epcoritamab or its' excipients.
5. Any AE related to the previous large cell lymphoma therapy which has not recovered
to Grade ≤ 1 (CTCAE v.5.0) or baseline by C1D1, except alopecia.
6. Use of any standard or experimental anti-large cell lymphoma therapy (including
nonpalliative radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any
other anticancer therapy) < 14 days prior to C1D1 (prednisone up to 50 mg or
equivalent for 5 days is permitted; palliative radiation is permitted only if on
non-target lesions).
7. Major surgery < 14 days of Cycle 1 Day 1.
8. Neuropathy Grade ≥ 2 (CTCAE v.5.0).
9. Patients with a history of other malignancies, except adequately treated
non-melanoma skin cancer, non-invasive superficial bladder cancer, curatively
treated in-situ cancer of the cervix, DCIS of the breast, localized low grade
prostate cancer (up to Gleason score 6), or other solid tumours curatively treated
with no evidence of disease for at least 3 years.
10. Active bacterial, viral, fungal, mycobacterial, parasitic, or other infection
(excluding fungal infections of nail beds) requiring systemic treatment within 7
days prior to the first dose of study treatment. Prophylactic antibacterial,
antiviral, and antifungal agents are allowed.
11. Confirmed history or current autoimmune disease or other diseases requiring
permanent immunosuppressive therapy. Low-dose (10 mg/day) prednisolone (or
equivalent) for rheumatoid arthritis or similar conditions is allowed.
12. Active HIV infection. NOTE: Testing for HIV antibody is required at the time of
screening. Those with positive HIV antibody will require HIV viral load by PCR
testing. Patients with detectable viral load will not be eligible for the study.
Those with positive antibody but undetectable viral load and CD4 >200 will be
eligible.
13. Testing for hepatitis B (HBV) and hepatitis C virus (HCV) is required at screening.
Hepatitis B testing will consist of Hepatitis B surface Antigen (HBsAg), Hepatitis B
Core Antibody (HBcAb) and Hepatitis Surface Antibody (HBsAb). Hepatitis C testing
will consist of Hepatitis C Antibody (HCAb). Subjects with a history of chronic
hepatitis B virus (HBV) infection must have an undetectable HBV viral load on
suppressive therapy, if indicated. Subjects with evidence of prior HBV but who are
PCR-negative are permitted in the trial but should receive prophylactic antiviral
therapy. Subjects with a history of hepatitis C virus (HCV) infection must have been
treated. For patients with HCV infection who are currently on treatment, the HCV
viral load must be undetectable to be eligible for this trial. Subjects who received
treatment for HCV that was intended to eradicate the virus may participate if
hepatitis C RNA levels are undetectable.
14. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while
the mother is being treated on study).
15. Any life-threatening illness, medical condition, or organ system dysfunction which,
in the Investigator's opinion, could compromise the subject's safety, or being
compliant with the study procedures.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Indiana University Melvin and Bren Simon Comprehensive Cancer Center
Address:
City:
Indianapolis
Zip:
46202
Country:
United States
Status:
Recruiting
Contact:
Last name:
Bobbie Frye
Email:
fryeba@iupui.edu
Investigator:
Last name:
Varun mITTAL, MD
Email:
Principal Investigator
Facility:
Name:
Karmanos Cancer Center (Wayne State University)
Address:
City:
Detroit
Zip:
48201
Country:
United States
Status:
Recruiting
Contact:
Last name:
Mary Jo O'Loughlin
Phone:
313-578-4405
Email:
oloughli@karmanos.org
Investigator:
Last name:
Dipenkumar Modi, MD
Email:
Principal Investigator
Start date:
October 31, 2023
Completion date:
November 2028
Lead sponsor:
Agency:
Dipenkumar Modi
Agency class:
Other
Collaborator:
Agency:
Genmab
Agency class:
Industry
Source:
Hoosier Cancer Research Network
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05852717
