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Trial Title:
Epcoritamab (Epcor)-Containing Combination Salvage Therapy Followed by ASCT & Epcor Consolidation in Patients With Relapsed LBCL
NCT ID:
NCT06287398
Condition:
DLBCL - Diffuse Large B Cell Lymphoma
High-grade B-cell Lymphoma
High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements
DLBCL, Nos Genetic Subtypes
High Grade B-Cell Lymphoma, Not Otherwise Specified
Follicular Large Cell Lymphoma, Relapsed
Follicular Large Cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Follicular
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Epcoritamab
Description:
Epcoritamab (Epcor) is a bispecific antibody recognizing the T-cell antigen CD3 and the
B-cell antigen CD20. Epcor is a supplied as a concentrate for solution for intended
subcutaneous injection. The dose must be prepared by a qualified pharmacist using aseptic
technique.
Epcoritamab-Salvage treatment phase:
2-3 cycles of R-DHAOx therapy (rituximab, dexamethasone, cytarabine, oxaliplatin), given
every 21 days combined with Epcoritamab subcutaneous weekly dosing (priming 0.16mg Cycle
1 Day 1, intermediate 0.8mg cycle 1 day 8, full dose 48mg from cycle 1 day 15 onwards)
Epcoritamab Consolidation phase:
6 cycles (28 days each) of subcutaneous Epcoritamab, commencing between 6-12 weeks post
ASCT.
Epcoritamab dosing and timing for consolidation:
- Cycle 1 Day 1: Priming (0.16mg) dose
- Cycle 1 Day 8: intermediate (0.8mg) dose
- Cycle 1 Day 15: full dose 48mg
- Cycle 1 Day 22, Cycle 2-3 Days 1, 8, 15 and 22: 48mg
- Cycles 4 to 6 - Days 1 and 15 (fortnightly dosing): 48mg
Arm group label:
Epcoritamab Treatment
Summary:
The goal of this clinical trial is to evaluate clinical efficacy of incorporating
Epcoritamab into the salvage treatment routine for relapsed-refractory aggressive B-cell
lymphoma, followed by autologous stem-cell transplantation (ASCT) and consolidation
Epcoritamab. The main questions it aims to answer are:
- Will the addition of epcoritamab to intensive salvage chemotherapy be safe and
increase the proportion of patients with relapsed or refractory (R/R) large B-cell
lymphoma who achieve a complete remission prior to planned transplant?
- Is consolidation epcoritamab after ASCT deliverable and safe?
- Will consolidation epcoritamab will result in improved clearance of molecularly
detectable residual disease?
- Will the combination of pre- and post-ASCT epcoritamab lead to higher rates of
progression-free survival (PFS) and event free survival (EFS) at 12 months compared
to historical estimates in this population.
Participants will undergo three phases in this trial:
1. Epcoritamab-Salvage treatment: consists of 3 cycles of R-DHAOx (rituximab,
dexamethasone, cytarabine, oxaliplatin) plus Epcoritamab
2. ASCT: Pre-autograft eligibility assessment for ASCT will be performed according to
local practice. ASCT may be administered at local referring centre and will follow
local standard operative procedures.
3. Consolidation treatment: consists of six 28-day cycles of subcutaneous Epcoritamab,
commencing 6 - 12 weeks post ASCT.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Age 18 years or older
2. Confirmed diagnosis of DLBCL, Not-otherwise specified (NOS), Transformation of
indolent B-cell lymphoma, High-grade B-cell lymphoma (HGBCL), NOS, Diffuse-large BCL
(DLBCL)/ High-grade B-cell lymphoma (HGBL) with MYC and BCL2 rearrangements or
Follicular large B-cell lymphoma according to World Health Organization (WHO) 2016
or 2022 criteria that has relapsed or progressed after one line of
chemoimmunotherapy
3. Transplant eligible according to local assessment
4. Eastern Cooperative Oncology Group (ECOG) performance status 0-2
5. Measurable disease on computed tomography (CT) scan, defined as a nodal site greater
than 1.5cm in longest axis or an extranodal site greater than 1.0cm in longest axis
AND baseline fluorodeoxyglucose (FDG) positron emission tomography (PET) scans must
demonstrate positive lesion compatible with CT defined anatomical tumour sites
6. Histological confirmation of tumour CD20 positivity, analysed by
immunohistochemistry, on a pre-enrolment tissue sample performed after most recent
prior therapy
7. Adequate renal function
- Creatinine clearance greater than 45mL per min (Cockcroft Gault formula)
8. Adequate hepatic function:
- Aspartate transaminase (AST) and alanine transaminase (ALT) less than or equal
to 3x Upper Limit of Normal (ULN)
- Bilirubin less than or equal to 1.5x Upper Limit of Normal (ULN) or less than
or equal to 3 if documented liver involvement and/or Gilbert's disease.
9. Adequate haematologic function:
- Haemoglobin greater than or equal to 90g/L (transfusion support permitted)
- Absolute neutrophil count greater than or equal to 1.0 x 109 per L; growth
factor support allowed in case of bone marrow involvement
- Platelet count greater than 75 x 109 per L or greater than or equal to 50 x 109
per L if documented marrow involvement
10. Able to take oral medications
11. Adequate washout of prior therapies:
- At least 4 weeks since last dose of immunochemotherapy, radio-conjugated or
toxin-conjugated compound, or other investigational anti-cancer therapy
- At least 6 weeks since chimeric antigen-receptor T-cell therapy
12. Resolution of toxicities from prior therapy to a grade that does not contraindicate
trial participation in the opinion of the investigator
13. If receiving glucocorticoid treatment at screening, treatment must be tapered down
and administered with a maximum of 25 mg daily in the last 14 days before the first
dose of Epcoritamab
14. Before the first dose of Epcoritamab, during the trial and for 12 months after last
administration of Epcoritamab, a woman must be either:
1. Not of childbearing potential, defined as: premenarchal; postmenopausal
(greater than 45 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
2. Of childbearing potential and practicing a highly effective method of birth
control (as defined by the European Clinical Trial Facilitation Group)
consistent with local regulations regarding the use of birth control methods
for patients participating in clinical trials: 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); male partner sterilization (the vasectomized partner should be the sole
partner for that patient); true abstinence (when this is in line with the
preferred and usual lifestyle of the patient) * If the childbearing potential
changes after start of the trial (e.g., woman who is not heterosexually active
becomes active, premenarchal woman experiences menarche) a woman must begin a
highly effective method of birth control, as described under 16b
15. A man who is sexually active with a woman of childbearing potential must agree to
use a barrier method of birth control (that is the use of condom) during the trial
and for 12 months after receiving the last dose of Epcoritamab
16. Women must agree not to donate eggs (ova, oocytes) for the purposes of assisted
reproduction during the trial and for 12 months after receiving the last dose of
Epcoritamab. Men must also not donate sperm during the trial and for 12 months after
receiving the last dose of Epcoritamab
17. The patient understands the purpose of the trial and procedures required for the
trial and is capable of giving signed informed consent which includes compliance
with the requirements (no medical or psychiatric reason precluding participation)
and restrictions listed in the informed consent form (ICF) and in this protocol
Exclusion Criteria:
1. Diagnosis of primary Central Nervous System (CNS) lymphoma
2. Active secondary CNS involvement of lymphoma at time of screening
- A prior history of secondary CNS lymphoma is allowed provided that it has been
successfully treated and there are no features of recurrence.
3. Prior autologous stem cell transplant
4. Known past or current malignancy other than inclusion diagnosis, except for:
1. Cervical carcinoma of Stage 1B or less.
2. Non-invasive basal cell or squamous cell skin carcinoma.
3. Non-invasive, superficial bladder cancer.
4. Prostate cancer with a current Prostate Specific Agent (PSA) level less than
0.1 ng per mL e. indolent lymphoma
5. Indolent lymphoma
6. Other malignancy that has been treated with curative intent and has remained in
remission for 2 years
5. Any prior therapy with a bispecific antibody targeting CD3 and CD20
6. Uncontrolled systemic infection
7. Known HIV infection
8. Known active hepatitis B or C infection based on criteria below:
- Hepatitis B virus (HBV): Patients with positive HbsAg are excluded. Patients
with positive hepatitis B core antibody (antiHBc) and negative HbsAg require
negative hepatitis B polymerase chain reaction (PCR) before enrolment and must
be treated with antiviral therapy. Patients who are hepatitis B PCR positive
will be excluded.
- Hepatitis C virus (HCV): If positive hepatitis C antibody, patient will need to
have a negative hepatitis C ribonucleic acid (RNA) before enrolment. Patients
who are hepatitis C RNA positive will be excluded.
9. Seizure disorder, unless seizure-free for 12 months on established anticonvulsant
therapy without the requirement for modification to anticonvulsants within the prior
12 months
10. Known clinically significant cardiac disease, including:
1. Onset of unstable angina pectoris within 6 months of signing the patient
informed consent form (PICF)
2. Acute myocardial infarction within 6 months of signing the PICF
3. Congestive heart failure (grade III or IV as classified by the New York Heart
Association
4. Decreased ejection fraction of less than 45%
11. Confirmed history or current autoimmune disease requiring permanent
immunosuppressive therapy. Low-dose prednisolone (less than or equal to 10mg/day or
equivalent) for rheumatoid arthritis or similar conditions is allowed.
12. Exposed to live or live attenuated vaccine within 4 weeks prior to signing PICF
13. Women who are pregnant or lactating.
14. Patient has any condition for which, in the opinion of the investigator,
participation would not be in the best interest of the patient (e.g., compromise the
well-being) or that could prevent, limit, or confound the protocol-specified
assessments
15. Known hypersensitivity or adverse reaction to rituximab, tocilizumab or any elements
of DHAOx
16. Presence of any psychological, familial, sociological or geographical condition
potentially hampering compliance with the study protocol and follow-up schedule.
This condition must be discussed with the patient prior to signing consent and
registration in the trial
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Australasian Leukemia and Lymphoma Group
Address:
City:
Melbourne
Zip:
3121
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Naomi Sprigg
Phone:
0383739706
Email:
Naomi.Sprigg@allg.org.au
Investigator:
Last name:
Adrian Minson, MD
Email:
Sub-Investigator
Start date:
December 11, 2023
Completion date:
November 2031
Lead sponsor:
Agency:
Australasian Leukaemia and Lymphoma Group
Agency class:
Other
Source:
Australasian Leukaemia and Lymphoma Group
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06287398