Trial Title:
Loncastuximab Tesirine and Rituximab Followed by DA-EPOCH-R for Treating Patients With High-Risk Diffuse Large B-cell Lymphoma
NCT ID:
NCT05600686
Condition:
Double-Expressor Lymphoma
High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements
High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements
High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements
Conditions: Official terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Prednisone
Cortisone
Cyclophosphamide
Rituximab
Doxorubicin
Liposomal doxorubicin
Etoposide
Vincristine
Etoposide phosphate
Daunorubicin
Podophyllotoxin
Loncastuximab tesirine
Antineoplastic Agents, Immunological
Antibodies
Immunoglobulins
Antibodies, Monoclonal
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:
Cyclophosphamide
Description:
Given IV
Arm group label:
Treatment (Lonca-R, DA-EPOCH-R)
Other name:
(-)-Cyclophosphamide
Other name:
2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
Other name:
Carloxan
Other name:
Ciclofosfamida
Other name:
Ciclofosfamide
Other name:
Cicloxal
Other name:
Clafen
Other name:
Claphene
Other name:
CP monohydrate
Other name:
CTX
Other name:
CYCLO-cell
Other name:
Cycloblastin
Other name:
Cycloblastine
Other name:
Cyclophospham
Other name:
Cyclophosphamid monohydrate
Other name:
Cyclophosphamide Monohydrate
Other name:
Cyclophosphamidum
Other name:
Cyclophosphan
Other name:
Cyclophosphane
Other name:
Cyclophosphanum
Other name:
Cyclostin
Other name:
Cyclostine
Other name:
Cytophosphan
Other name:
Cytophosphane
Other name:
Cytoxan
Other name:
Fosfaseron
Other name:
Genoxal
Other name:
Genuxal
Other name:
Ledoxina
Other name:
Mitoxan
Other name:
Neosar
Other name:
Revimmune
Other name:
Syklofosfamid
Other name:
WR- 138719
Intervention type:
Drug
Intervention name:
Doxorubicin
Description:
Given IV
Arm group label:
Treatment (Lonca-R, DA-EPOCH-R)
Other name:
Adriablastin
Other name:
Hydroxydaunomycin
Other name:
Hydroxyl Daunorubicin
Other name:
Hydroxyldaunorubicin
Intervention type:
Drug
Intervention name:
Etoposide
Description:
Given IV
Arm group label:
Treatment (Lonca-R, DA-EPOCH-R)
Other name:
Demethyl Epipodophyllotoxin Ethylidine Glucoside
Other name:
EPEG
Other name:
Lastet
Other name:
Toposar
Other name:
Vepesid
Other name:
VP 16
Other name:
VP 16-213
Other name:
VP-16
Other name:
VP-16-213
Other name:
VP16
Intervention type:
Biological
Intervention name:
Loncastuximab Tesirine
Description:
Given IV
Arm group label:
Treatment (Lonca-R, DA-EPOCH-R)
Other name:
ADC ADCT-402
Other name:
ADCT-402
Other name:
Anti-CD19 PBD-conjugate ADCT-402
Other name:
Loncastuximab Tesirine-lpyl
Other name:
Zynlonta
Intervention type:
Drug
Intervention name:
Prednisone
Description:
Given PO
Arm group label:
Treatment (Lonca-R, DA-EPOCH-R)
Other name:
.delta.1-Cortisone
Other name:
1, 2-Dehydrocortisone
Other name:
Adasone
Other name:
Cortancyl
Other name:
Dacortin
Other name:
DeCortin
Other name:
Decortisyl
Other name:
Decorton
Other name:
Delta 1-Cortisone
Other name:
Delta-Dome
Other name:
Deltacortene
Other name:
Deltacortisone
Other name:
Deltadehydrocortisone
Other name:
Deltasone
Other name:
Deltison
Other name:
Deltra
Other name:
Econosone
Other name:
Lisacort
Other name:
Meprosona-F
Other name:
Metacortandracin
Other name:
Meticorten
Other name:
Ofisolona
Other name:
Orasone
Other name:
Panafcort
Other name:
Panasol-S
Other name:
Paracort
Other name:
Perrigo Prednisone
Other name:
PRED
Other name:
Predicor
Other name:
Predicorten
Other name:
Prednicen-M
Other name:
Prednicort
Other name:
Prednidib
Other name:
Prednilonga
Other name:
Predniment
Other name:
Prednisone Intensol
Other name:
Prednisonum
Other name:
Prednitone
Other name:
Promifen
Other name:
Rayos
Other name:
Servisone
Other name:
SK-Prednisone
Intervention type:
Biological
Intervention name:
Rituximab
Description:
Given IV
Arm group label:
Treatment (Lonca-R, DA-EPOCH-R)
Other name:
ABP 798
Other name:
BI 695500
Other name:
C2B8 Monoclonal Antibody
Other name:
Chimeric Anti-CD20 Antibody
Other name:
CT-P10
Other name:
IDEC-102
Other name:
IDEC-C2B8
Other name:
IDEC-C2B8 Monoclonal Antibody
Other name:
MabThera
Other name:
Monoclonal Antibody IDEC-C2B8
Other name:
PF-05280586
Other name:
Riabni
Other name:
Rituxan
Other name:
Rituximab ABBS
Other name:
Rituximab ARRX
Other name:
Rituximab Biosimilar ABP 798
Other name:
Rituximab Biosimilar BI 695500
Other name:
Rituximab Biosimilar CT-P10
Other name:
Rituximab Biosimilar GB241
Other name:
Rituximab Biosimilar IBI301
Other name:
Rituximab Biosimilar JHL1101
Other name:
Rituximab Biosimilar PF-05280586
Other name:
Rituximab Biosimilar RTXM83
Other name:
Rituximab Biosimilar SAIT101
Other name:
Rituximab Biosimilar SIBP-02
Other name:
rituximab biosimilar TQB2303
Other name:
Rituximab PVVR
Other name:
rituximab-abbs
Other name:
Rituximab-arrx
Other name:
Rituximab-pvvr
Other name:
RTXM83
Other name:
Ruxience
Other name:
Truxima
Intervention type:
Drug
Intervention name:
Vincristine
Description:
Given IV
Arm group label:
Treatment (Lonca-R, DA-EPOCH-R)
Other name:
Leurocristine
Other name:
VCR
Other name:
Vincrystine
Summary:
This phase II trial evaluates whether loncastuximab tesirine and rituximab followed by
dose-adjusted doxorubicin, etoposide, vincristine, cyclophosphamide, and prednisone works
to treat patients with high risk diffuse large B-cell lymphoma. Loncastuximab tesirine is
a monoclonal antibody called loncastuximab, linked to a drug called tesirine. It is a
form of targeted therapy because it attaches to specific molecules (receptors) on the
surface of cancer cells, known as CD19 receptors, and delivers tesirine to kill them.
Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on
B cells (a type of white blood cell) and some types of cancer cells. This may help the
immune system kill cancer cells. Chemotherapy drugs such as doxorubicin, vincristine, and
cyclophosphamide work in different ways to stop the growth of cancer cells, either by
killing the cells, by stopping them from dividing, or by stopping them from spreading.
Etoposide is in a class of medications known as podophyllotoxin derivatives. It blocks a
certain enzyme needed for cell division and DNA repair and may kill cancer cells.
Prednisone is in a class of medications called corticosteroids. It is used to reduce
inflammation and lower the body's immune response to help lessen the side effects of
chemotherapy drugs. Giving loncastuximab tesirine and rituximab in combination with
dose-adjusted doxorubicin, etoposide, vincristine, cyclophosphamide, and prednisone may
be more effective at treating high risk diffuse large B-cell lymphoma patients than
standard treatments.
Detailed description:
PRIMARY OBJECTIVE:
I. To obtain a preliminary estimate of the anti-tumor activity of loncastuximab tesirine
and rituximab (lonca-R) in newly diagnosed double-expressor lymphoma (DEL) and double-hit
lymphoma (DHL).
SECONDARY OBJECTIVES:
I. To obtain additional efficacy measures of lonca-R in newly diagnosed DEL and DHL.
II. To assess safety and tolerability of lonca-R followed by dose-adjusted doxorubicin,
etoposide, vincristine, cyclophosphamide, and prednisone (DA-EPOCH-R) as coded by Common
Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
OUTLINE:
Patients receive rituximab intravenously (IV), loncastuximab tesirine IV, etoposide IV,
doxorubicin IV, vincristine IV, prednisone orally (PO), and cyclophosphamide IV on study.
Patients also undergo collection of blood samples and bone marrow aspiration and biopsy
at screening and computed tomography (CT) or positron emission tomography (PET)/CT at
screening, throughout the study, and during follow up.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Histologically or cytologically confirmed untreated DEL and DHL diffuse large B-cell
lymphoma (DLBCL) meeting the World Health Organization (WHO) criteria for DEL - MYC
greater than 40% and BCL2 greater than 50% by immunohistochemistry, or high-grade
B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements (double-hit and/or
triple-hit are included)
- Measurable disease by CT or PET/CT scan, with one or more sites of disease >= 1.5 cm
in longest dimension
- Age >= 18 years at time of consent
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- Life expectancy >= 6 months
- Leukocytes >= 2,500/uL
- Absolute neutrophil count >= 1,000/uL
- Platelets >= 100,000/uL
- Hemoglobin >= 8 g/dL
- Total bilirubin =< 1.5 x institutional upper limit of normal (ULN) (however,
patients with known Gilbert disease who have serum bilirubin level =< 3 x ULN may be
enrolled)
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase
[SGPT]) =< 3 x ULN (AST and/or ALT =< 5 x ULN for patients with liver involvement)
- Alkaline phosphatase =< 2.5 x ULN (=< 5 x ULN for patients with documented liver
involvement or bone metastases)
- Creatinine clearance >= 30 mL/min by Cockcroft-Gault
- Activated partial thromboplastin time (aPTT) =< 1.5 x ULN (This applies only to
patients who do not receive therapeutic anticoagulation; patients receiving
therapeutic anticoagulation, such as low-molecular-weight heparin or warfarin,
should be on a stable dose)
- Transthoracic echocardiography (TTE) or multigated acquisition scan (MUGA) ejection
fraction greater than 40%
- Women of child-bearing potential (WOCBP) must agree to use a highly effective method
of contraception from the time of giving informed consent until at least 10 months
after the last dose of study drug. Men with female partners who are of childbearing
potential must agree to use a highly effective method of contraception from the time
of giving informed consent until at least 7 months after the last dose of study drug
- Ability to understand and the willingness to sign a written informed consent
document
- Human immunodeficiency virus (HIV) infected patients:
- No history of acquired immunodeficiency syndrome (AIDS)-defining conditions
other than lymphoma or history of CD4+ T-cells below 200/mm^3 prior to
beginning combination anti-retroviral therapy (ART)
- Human immunodeficiency virus (HIV)-infected patients on effective
anti-retroviral therapy with undetectable viral load within 6 months are
eligible for this trial
- At time of study entry CD4+ T-cells must have recovered from prior lymphoma
therapy to >= 250/mm^3
- At the time of study entry, the HIV viral load must be undetectable by standard
laboratory assay
- During prior lymphoma therapy, patients must not have experienced documented
infections attributed to the HIV positive (+) status
- No history of non-adherence to ART and willing to adhere to ART while on study
- Antiretroviral drugs with overlapping or similar toxicity profiles as study
agents not allowed
Exclusion Criteria:
- Current/ prior use of:
- Lymphoma treatment, except for:
- 1 cycle of DA-EPOCH-R or rituximab, cyclophosphamide, doxorubicin
(Adriamycin) vincristine (Oncovin) and prednisolone (R-CHOP)
- Radiotherapy > 2 weeks of initiating study treatment
- Nitrosoureas or mitomycin C > 6 weeks of initiating study treatment
- Steroid treatment for DLBCL or steroid monotherapy to stabilize disease
while awaiting fluorescence in situ hybridization (FISH)
- Other cancer therapies (e.g., prostate, breast hormonal-based therapy) per
the principal investigator's discretion
- Anthracycline greater than 50 mg/m^2 (total lifetime) for a prior malignancy
- Complementary and alternative medications (CAM) within 1 week prior to
initiating study treatment
- Treatment with any other investigational agent for any indication within 3
weeks prior to initiating study treatment
- Loncastuximab tesirine or rituximab with progression within 6 months of
initiating study treatment
- Oral or intravenous (IV) antibiotics within 2 weeks prior to initiating study
treatment. Patients receiving prophylactic antibiotics (e.g., for prevention of
a urinary tract infection or chronic obstructive pulmonary disease) are
eligible
- Live, attenuated influenza vaccine within 4 weeks prior to initiating study
treatment
- Immunosuppressive medications (including, but not limited to, cyclophosphamide,
azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor, such as
anti-tumor necrosis factor [TNF] agents) within 14 days prior to initiating study
treatment. The following are exceptions to this criterion:
- Steroids
- Bisphosphonate therapy for symptomatic hypercalcemia or for other reasons
(e.g., bone metastasis or osteoporosis)
- Known uncontrolled central nervous system (CNS) involvement by lymphoma, including
leptomeningeal involvement
- History of hypersensitivity to anti-CD19 antibodies, loncastuximab tesirine, or any
agents used in DA-EPOCH-R
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to other agents used in study
- Clinically significant third space fluid accumulation (i.e., ascites requiring
drainage or pleural effusion that is either requiring drainage or associated with
shortness of breath)
- Breastfeeding or pregnancy
- Clinically significant liver disease, including active viral, alcoholic, or other
hepatitis; cirrhosis; fatty liver; or inherited liver disease
- Patients with past or resolved hepatitis B infection (defined as having a
negative hepatitis B surface antigen [HbsAg] test and a positive anti-HBc
[antibody to hepatitis B core antigen] antibody test) are eligible
- Patients positive for hepatitis C virus (HCV) antibody are eligible only if
polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA)
- Documented eczema, psoriasis, or lichen simplex chronicus of vitiligo with
dermatologic manifestations (e.g., patients with psoriatic arthritis would be
excluded), unless the following apply:
- Affected skin covers less than 10% of body surface area (BSA)
- Disease is well controlled at baseline and only requires low potency topical
steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone
0.01%, desonide 0.05%, alclometasone dipropionate 0.05%)
- No acute exacerbations of underlying condition within the last 12 months (not
requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate,
retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral
steroids)
- Known active tuberculosis (TB)
- Severe infections within 4 weeks prior to initiating study treatment, including, but
not limited to, hospitalization for complications of infection, bacteremia, or
severe pneumonia
- Major surgical procedure within 28 days prior to initiating study treatment or
anticipation of need for a major surgical procedure during the course of the study
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance
with study requirements
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of California Davis Comprehensive Cancer Center
Address:
City:
Sacramento
Zip:
95817
Country:
United States
Status:
Recruiting
Contact:
Last name:
Selina Laqui
Phone:
916-734-0565
Email:
slaqui@ucdavis.edu
Investigator:
Last name:
Joseph M. Tuscano
Email:
Principal Investigator
Start date:
May 24, 2023
Completion date:
February 1, 2028
Lead sponsor:
Agency:
Joseph Tuscano
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Collaborator:
Agency:
ADC Therapeutics S.A.
Agency class:
Industry
Source:
University of California, Davis
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05600686
