Trial Title:
Tafasitamab and Lenalidomide Followed by Tafasitamab and ICE as Salvage Therapy for Transplant Eligible Patients With Relapsed/ Refractory Large B-Cell Lymphoma
NCT ID:
NCT05821088
Condition:
Recurrent B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma
Recurrent Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
Recurrent Grade 3b Follicular Lymphoma
Recurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements
Recurrent High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements
Recurrent High Grade B-Cell Lymphoma, Not Otherwise Specified
Recurrent Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type
Recurrent Primary Mediastinal (Thymic) Large B-Cell Lymphoma
Recurrent T-Cell/Histiocyte-Rich Large B-Cell Lymphoma
Recurrent Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma
Recurrent Transformed Marginal Zone Lymphoma to Diffuse Large B-Cell Lymphoma
Refractory B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin Lymphoma
Refractory Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
Refractory Grade 3b Follicular Lymphoma
Refractory High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements
Refractory High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements
Refractory High Grade B-Cell Lymphoma, Not Otherwise Specified
Refractory Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type
Refractory Primary Mediastinal (Thymic) Large B-Cell Lymphoma
Refractory T-Cell/Histiocyte-Rich Large B-Cell Lymphoma
Refractory Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma
Refractory Transformed Marginal Zone Lymphoma to Diffuse Large B-Cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, B-Cell
Hodgkin Disease
Lymphoma, Large B-Cell, Diffuse
Lymphoma, B-Cell, Marginal Zone
Recurrence
Carboplatin
Etoposide
Lenalidomide
Etoposide phosphate
Ifosfamide
Isophosphamide mustard
Podophyllotoxin
Immunoglobulins
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:
Procedure
Intervention name:
Biopsy
Description:
Undergo tissue biopsy
Arm group label:
Treatment (tafasitamab, lenalidomide, ICE regimen)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (tafasitamab, lenalidomide, ICE regimen)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Drug
Intervention name:
Carboplatin
Description:
Given IV
Arm group label:
Treatment (tafasitamab, lenalidomide, ICE regimen)
Other name:
Blastocarb
Other name:
Carboplat
Other name:
Carboplatin Hexal
Other name:
Carboplatino
Other name:
Carboplatinum
Other name:
Carbosin
Other name:
Carbosol
Other name:
Carbotec
Other name:
CBDCA
Other name:
Displata
Other name:
Ercar
Other name:
JM-8
Other name:
Nealorin
Other name:
Novoplatinum
Other name:
Paraplatin
Other name:
Paraplatin AQ
Other name:
Paraplatine
Other name:
Platinwas
Other name:
Ribocarbo
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Treatment (tafasitamab, lenalidomide, ICE regimen)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Etoposide
Description:
Given IV
Arm group label:
Treatment (tafasitamab, lenalidomide, ICE regimen)
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:
Drug
Intervention name:
Ifosfamide
Description:
Given IV
Arm group label:
Treatment (tafasitamab, lenalidomide, ICE regimen)
Other name:
Asta Z 4942
Other name:
Asta Z-4942
Other name:
Cyfos
Other name:
Holoxan
Other name:
Holoxane
Other name:
Ifex
Other name:
IFO
Other name:
IFO-Cell
Other name:
Ifolem
Other name:
Ifomida
Other name:
Ifomide
Other name:
Ifosfamidum
Other name:
Ifoxan
Other name:
IFX
Other name:
Iphosphamid
Other name:
Iphosphamide
Other name:
Iso-Endoxan
Other name:
Isoendoxan
Other name:
Isophosphamide
Other name:
Mitoxana
Other name:
MJF 9325
Other name:
MJF-9325
Other name:
Naxamide
Other name:
Seromida
Other name:
Tronoxal
Other name:
Z 4942
Other name:
Z-4942
Intervention type:
Drug
Intervention name:
Lenalidomide
Description:
Given PO
Arm group label:
Treatment (tafasitamab, lenalidomide, ICE regimen)
Other name:
CC-5013
Other name:
CC5013
Other name:
CDC 501
Other name:
Revlimid
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET
Arm group label:
Treatment (tafasitamab, lenalidomide, ICE regimen)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
Intervention type:
Biological
Intervention name:
Tafasitamab
Description:
Given IV
Arm group label:
Treatment (tafasitamab, lenalidomide, ICE regimen)
Other name:
Immunoglobulin, Anti-(Human Cd19 Antigen) (Human-mus musculus Monoclonal MOR00208 Heavy Chain), Disulfide with Human-mus musculus Monoclonal MOR00208 .Kappa.-chain, Dimer
Other name:
Monjuvi
Other name:
MOR-00208
Other name:
MOR00208
Other name:
MOR208
Other name:
Tafasitamab-cxix
Other name:
XmAb5574
Summary:
This phase II clinical trial evaluates tafasitamab and lenalidomide followed by
tafasitamab and the carboplatin, etoposide and ifosfamide (ICE) regimen as salvage
therapy for transplant eligible patients with large B-cell lymphoma that has come back
(relapsed) or has not responded to treatment (refractory). Tafasitamab is a monoclonal
antibody that may interfere with the ability of cancer cells to grow and spread.
Lenalidomide may have antineoplastic activity which may help block the formation of
growths that may become cancer. Drugs used in chemotherapy, such as carboplatin,
etoposide and ifosfamide 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. Giving tafasitamab and lenalidomide followed by ICE may be a better treatment
for patients with relapsed or refractory large B-cell lymphomas.
Detailed description:
PRIMARY OBJECTIVE:
I. Evaluate the anti-tumor activity of tafasitamab and lenalidomide followed by
tafasitamab and ICE as first salvage therapy for relapsed/ refractory large B cell
lymphoma as assessed by the cumulative complete response rate after completion of 2 or 4
cycles of study treatment.
SECONDARY OBJECTIVES:
I. Evaluate the overall response rate to tafasitamab and lenalidomide followed by
tafasitamab and ICE in transplant eligible patients with relapsed/ refractory large B
cell lymphoma after 2-4 total cycles of treatment.
II. Evaluate the overall and complete response rate to tafasitamab and lenalidomide after
two cycles of treatment in transplant eligible patients with relapsed/ refractory large B
cell lymphoma.
III. Evaluate the rate of successful stem cell mobilization following study treatment.
IV. Evaluate the rate of successful completion of autologous stem cell transplant (ASCT)
following study treatment, including patients treated with a total of 2 or 4 cycles of
treatment.
V. Evaluate the incidence of toxicities according to Common Terminology Criteria for
Adverse Events (CTCAE) Version 5.
VI. Evaluate the progression free and overall survival in the study population. VII.
Compare progression free survival (PFS)/ overall survival (OS) (i.e. long-term outcomes)
in patients who proceed to transplant after completing only 2 cycles of
tafasitamab/lenalidomide (tafa/len) versus those completing 4 cycles of tafa/len followed
by tafa+ICE.
EXPLORATORY OBJECTIVES:
I. Evaluate the response rate to subsequent anti-CD19 CAR-T treatment in patients who go
on to receive further therapy including for relapsed/ refractory disease.
II. Assess CD19 expression in patients with subsequent relapse or refractory disease
following study treatment by immunohistochemistry.
III. Examine the association between clinical outcomes including complete response (CR)
rate and pathological tumor characteristics (e.g. in activated B-cell [ABC]-type subgroup
by gene expression profiling [GEP], non-germinal center [GC] subtype by Hans,
"double/triple hit" phenotype by fluorescence in situ hybridization [FISH] and/or GEP).
IV. Examine the association between circulating tumor deoxyribonucleic acid (ctDNA)
clearance and clinical outcomes including CR rate and PFS.
V. Evaluate association between clinical outcomes and duration of response to first-line
therapy < 12 months vs > 12 months.
OUTLINE:
Patients receive tafasitamab intravenously (IV), lenalidomide orally (PO), etoposide IV,
ifosfamide IV and carboplatin IV on study. Patients undergo positron emission tomography
(PET) or computed tomography (CT), and undergo blood sample collection throughout the
study. Patients may undergo tissue biopsy on study.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Adult patient (age 18 or older)
- Willing and able to provide written informed consent for the trial, assent when
appropriate may be obtained per institutional guidelines
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Considered transplant eligible by the treating physician
- Measurable disease by CT (defined as >= 1.5 cm in diameter) or one or more area of
PET avid disease
- Have received one line of prior chemo-immunotherapy (i.e. cyclophosphamide,
doxorubicin, prednisone, rituximab and vincristine [R-CHOP]). Note that
corticosteroids for palliation of symptoms and radiation consolidation are not
considered a line of therapy for purposes of eligibility determination
- Eligible histologic diagnosis includes: Diffuse large B cell lymphoma not otherwise
specified (NOS), T cell histiocyte rich large B cell lymphoma, primary mediastinal B
Cell lymphoma, follicular lymphoma grade 3B, high grade B cell lymphoma with MYC and
BCL2 and/or BCL6 rearrangement, high grade B cell lymphoma NOS, DLBCL transformed
from follicular lymphoma, DLBCL transformed from marginal zone lymphoma, DLBCL leg
type, and B cell lymphoma unclassifiable (with features intermediate between DLBCL
and classical Hodgkin's lymphoma)
- Absolute neutrophil count >= 1000 / mcL
- Platelets >= 75,000 / mcL in absence of transfusion support within 7 days of
determining eligibility
- Hemoglobin >= 8.0 g/dL, with exception of cases in which cytopenias are due to
marrow involvement by lymphoma
- Serum total bilirubin =< 1.5 x upper limit of normal (ULN) (except in patients with
Gilbert Syndrome who can have total bilirubin < 3.0 mg/dL)
- Aspartate transaminase (AST) and alanine transaminase (ALT) =< 3.0 x ULN
- Serum creatinine clearance >= 60 mL/min (calculated according to institutional
standard)
- Female subjects of childbearing potential should have a negative serum pregnancy
test at screening and within 24 hours of receiving the first dose of study
medication
- Female subjects of childbearing potential should be willing to use 2 methods of
birth control or be surgically sterile, or abstain from heterosexual activity for
the course of the study through 3 months following the last dose of study treatment.
Subjects should agree to ongoing pregnancy testing during the course of the study
and after the end of study therapy. Subjects of childbearing potential are patients
who have not been surgically sterilized and have not been free from menses for > 1
year
- Male subjects should agree to use an adequate method of contraception starting with
the first dose of study therapy through 3 months after the last dose of study
therapy. Males must refrain from donating sperm during study participation and for 3
months after last dose of study medication
- In the opinion of the investigator, patients must be able and willing to receive
adequate prophylaxis and/or therapy for thromboembolic events and be able to
understand the reason for complying with the special conditions of the pregnancy
prevention risk management plan
- Willing to provide archival tissue from biopsy performed after frontline systemic
therapy (If prior archival tissue is unavailable, exceptions may be granted by the
study principal investigator [PI])
Exclusion Criteria:
- Known active central nervous system involvement by lymphoma, including
leptomeningeal involvement
- DLBCL transformed from chronic lymphocytic leukemia or small lymphocytic lymphoma
(Richter's syndrome)
- Prior solid organ transplant
- Prior hematopoietic cell transplant
- History of other malignancy that could affect compliance with the protocol or
interpretation of results in the opinion of the investigator
- Myocardial infarction or cerebrovascular accident within the past 6 months
- Clinically significant cardiovascular disease including uncontrolled arrhythmia or
New York Heart Association Class 2-4 congestive heart failure
- Active uncontrolled infection or infection requiring IV antibiotic therapy
- Major surgery within 4 weeks prior to start of treatment other than surgery
performed for diagnosis
- Prior lymphoma therapy should be completed greater than two weeks from the start of
protocol therapy, with exception of patients receiving corticosteroids for
palliation of symptoms
- Human immunodeficiency virus (HIV) infection AND CD4 count < 350 cells/ mm^3,
evidence of resistant strain of HIV, or HIV viral load >= 50 copies HIV ribonucleic
acid (RNA)/mL if on highly active antiretroviral therapy (HAART) or HIV viral load
>= 10,000 copies HIV RNA/mL if not on anti-HIV therapy
- Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Patients
with past HBV infection (defined as negative hepatitis B surface antigen [HBsAg] and
positive hepatitis B core antibody [HBcAb]) are eligible if HBV DNA is undetectable.
Patients who are positive for HCV antibody are eligible if polymerase chain reaction
(PCR) is negative for HCV RNA. Testing to be done only in patients suspected of
having infections or exposures
- Known contraindication to any medication in the treatment plan, including known
hypersensitivity
- Prior treatment with anti-CD19 targeted therapy or lenalidomide
- Gastrointestinal abnormalities including the inability to take oral medication,
requirement of intravenous alimentation, or prior surgical procedure resulting in
impaired enteral absorption of medication
- History or evidence of rare hereditary problems of galactose intolerance, the Lapp
lactase deficiency, or glucose-galactose malabsorption
- History of deep venous thromboembolism threatening thromboembolism, or known
thrombophilia AND not willing to take venous thromboembolism prophylaxis during the
study period
- Patients who in the opinion of the investigator have not recovered sufficiently from
the adverse toxic events of prior therapy
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Ohio State University Comprehensive Cancer Center
Address:
City:
Columbus
Zip:
43210
Country:
United States
Status:
Recruiting
Contact:
Last name:
David A. Bond, MD
Phone:
614-293-3196
Email:
David.Bond@osumc.edu
Investigator:
Last name:
David A. Bond, MD
Email:
Principal Investigator
Start date:
June 29, 2023
Completion date:
December 31, 2025
Lead sponsor:
Agency:
David Bond, MD
Agency class:
Other
Source:
Ohio State University Comprehensive Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05821088
http://cancer.osu.edu
