Trial Title:
Tafasitamab, Lenalidomide and Venetoclax for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma
NCT ID:
NCT05910801
Condition:
Recurrent Mantle Cell Lymphoma
Refractory Mantle Cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, Mantle-Cell
Lenalidomide
Venetoclax
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 biopsy
Arm group label:
Treatment (Tafasitamab, lenalidomide, venetoclax)
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, venetoclax)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Bone Marrow Aspiration
Description:
Undergo bone marrow aspiration
Arm group label:
Treatment (Tafasitamab, lenalidomide, venetoclax)
Intervention type:
Procedure
Intervention name:
Bone Marrow Biopsy
Description:
Undergo bone marrow biopsy
Arm group label:
Treatment (Tafasitamab, lenalidomide, venetoclax)
Other name:
Biopsy of Bone Marrow
Other name:
Biopsy, Bone Marrow
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT scan
Arm group label:
Treatment (Tafasitamab, lenalidomide, venetoclax)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Lenalidomide
Description:
Given PO
Arm group label:
Treatment (Tafasitamab, lenalidomide, venetoclax)
Other name:
CC-5013
Other name:
CC5013
Other name:
CDC 501
Other name:
Revlimid
Intervention type:
Procedure
Intervention name:
Lumbar Puncture
Description:
Undergo lumbar puncture
Arm group label:
Treatment (Tafasitamab, lenalidomide, venetoclax)
Other name:
LP
Other name:
Spinal Tap
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (Tafasitamab, lenalidomide, venetoclax)
Other name:
Magnetic Resonance
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET/CT scan
Arm group label:
Treatment (Tafasitamab, lenalidomide, venetoclax)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron emission tomography (procedure)
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, venetoclax)
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
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
Given PO
Arm group label:
Treatment (Tafasitamab, lenalidomide, venetoclax)
Other name:
ABT-0199
Other name:
ABT-199
Other name:
ABT199
Other name:
GDC-0199
Other name:
RG7601
Other name:
Venclexta
Other name:
Venclyxto
Summary:
This phase II trial tests how well tafasitamab, lenalidomide and venetoclax work in
treating patients with mantle cell lymphoma that has come back (after a period of
improvement) (relapsed) or that has not responded to previous treatment (refractory).
Tafasitamab is a monoclonal antibody that may interfere with the ability of cancer cells
to grow and spread. Lenalidomide is in a class of medications called immunomodulatory
agents. It works by helping the immune system kill cancer cells. Venetoclax is in a class
of medications called B-cell lymphoma-2 (Bcl-2) inhibitors. It may stop the growth of
cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving
tafasitamab, lenalidomide and venetoclax together may kill cancer cells more efficiently
in patients with relapsed or refractory mantle cell lymphoma.
Detailed description:
PRIMARY OBJECTIVE:
I. To evaluate the overall response rate in patients with relapsed/refractory mantle cell
lymphoma after treatment with tafasitamab, lenalidomide and venetoclax combination.
SECONDARY OBJECTIVES:
I. To estimate the complete response rate in patients with relapsed/refractory mantle
cell lymphoma after treatment with tafasitamab, lenalidomide and venetoclax combination.
II. To estimate the duration of response (DoR) in patients with relapsed/refractory
mantle cell lymphoma after treatment with tafasitamab, lenalidomide and venetoclax
combination.
III. To estimate the progression free survival (PFS) in patients with relapsed/refractory
mantle cell lymphoma after treatment with tafasitamab, lenalidomide and venetoclax
combination.
IV. To estimate the overall survival (OS) in patients with relapsed/refractory mantle
cell lymphoma after treatment with tafasitamab, lenalidomide and venetoclax combination.
V. To evaluate the safety profile of tafasitamab, lenalidomide and venetoclax combination
in patients with relapsed/refractory mantle cell lymphoma.
CORRELATIVE OBJECTIVES:
I. To assess the rate of undetectable minimal residual disease (uMRD) in peripheral blood
by multi-color flow cytometry.
II. To assess the correlation between MRD status with clinical outcomes such as DoR, PFS
and OS.
OUTLINE: Patients receive tafasitamab intravenously (IV), lenalidomide orally (PO) and
venetoclax PO while on study. Patients may undergo lumbar puncture during screening.
Patients undergo computed tomography (CT) scan and blood sample collection and may
undergo magnetic resonance imaging (MRI) and tumor biopsy on study and during follow-up.
Patients undergo positron emission tomography (PET)/CT, bone marrow biopsy, and bone
marrow aspirate throughout the study.
After treatment completion, patients follow up every 3 months for 1 year, every 4 months
for 1 year and then every 6 months until up to 5 years after entering the trial.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Age >= 18 years old
- Confirmed pathology diagnosis of mantle cell lymphoma (MCL) with t(11;14)(q13;q32)
translocation or cyclin D1 overexpression NOTE: Patients with relapsed/refractory
MCL after prior anti-CD19 therapy (such as chimeric antigen receptor [CAR] T-cell
therapy) should have confirmed preserved expression of CD19, unless a biopsy is not
feasible or associated with a high risk of complications in the treating physician's
opinion
- Relapsed or refractory disease, which is defined as patients with >= 1 line of prior
systemic treatment NOTE: Prior exposure to lenalidomide or venetoclax is allowed,
provided there was no disease progression on lenalidomide or venetoclax
- In the view of the treating physician, the patient is in need of treatment, for
example, with lymphoma-related symptoms or cytopenia
- Evaluable disease, which is defined as at least one lymph node or other type of
lesion that has a size >= 1.5 cm, or spleen size >= 15 cm or white blood cell (WBC)
>= 30,000/mm^3 in leukemic non-nodal MCL patients
- Eastern Cooperative Oncology Group Performance Status (PS) 0, 1, or 2
- Absolute neutrophil count (ANC) >= 1500/mm^3 (obtained =< 14 days prior to
registration)
- Platelet count >= 75,000/mm^3 (>= 50,000/mm^3 if there is evidence of bone marrow
involvement by MCL or hypersplenism) (obtained =< 14 days prior to registration)
- Hemoglobin > 8.0 g/dL (obtained =< 14 days prior to registration)
- Activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) =<
1.5 × upper normal limit (ULN) (obtained =< 14 days prior to registration)
- Prothrombin (PT) or international normalized ratio (INR) =< 1.5 × upper normal limit
(ULN) (obtained =< 14 days prior to registration)
- Total bilirubin =< 1.5 × ULN (or =< 3 × ULN if there is evidence of parenchymal
liver involvement with MCL or documented Gilbert's disease) (obtained =< 14 days
prior to registration)
- Alanine aminotransferase (ALT) and aspartate transaminase (AST) =< 3 × ULN (or =< 5
× ULN if there is evidence of parenchymal liver involvement with MCL) (obtained =<
14 days prior to registration)
- Calculated creatinine clearance > 60 ml/min using the Cockcroft-Gault formula
(obtained =< 14 days prior to registration)
- Negative pregnancy test done =< 7 days prior to registration, for women of
reproductive potential only NOTE: If the urine test is positive or cannot be
confirmed as negative, a serum pregnancy test will be required NOTE: Females of
reproductive potential include all females who are menstruating, amenorrheic from
previous medical treatments, under 50 years of age, and/or perimenopausal, and do
not qualify for the females not of reproductive potential category. Females not of
reproductive potential include females who have been in natural menopause for at
least 24 consecutive months, or who have had a hysterectomy and/or bilateral
oophorectomy, or female children who have not started menstruating
- Agree to use effective contraception during study treatment and for 4 weeks after
last dose of lenalidomide and for 3 months after last dose of tafasitamab (whichever
is longer) Females of reproductive potential must commit either to abstain
continuously from heterosexual sexual intercourse or to use two methods of reliable
birth control simultaneously: one highly effective form of contraception - tubal
ligation, intrauterine device (IUD), hormonal (birth control pills, injections,
hormonal patches, vaginal rings, or implants), or partner's vasectomy, and one
additional effective contraceptive method - male latex or synthetic condom,
diaphragm, or cervical cap. Contraception should continue during therapy, during
dose interruptions, and for 4 weeks following discontinuation of lenalidomide and
for 3 months after discontinuation of tafasitamab (whichever is longer). Reliable
contraception is indicated even where there has been a history of infertility,
unless due to hysterectomy. If needed, females of reproductive potential should be
referred to a qualified provider of contraceptive methods Males must always use a
latex or synthetic condom during any sexual contact with females of reproductive
potential during trial therapy, during dose interruptions, and for 4 weeks following
discontinuation of lenalidomide and for 3 months after discontinuation of
tafasitamab (whichever is longer), even if they have undergone a successful
vasectomy. Male patients must not donate sperm
- Willing to be registered into the mandatory REVLIMID REMS (trademark) program, and
willing and able to comply with the requirements of the REVLIMID REMS program
- Able to take low-dose aspirin (81 mg) daily or an alternative form of
anticoagulation
- Subject must voluntarily sign and date an informed consent =< 28 days prior to
registration
- Willing to return to enrolling institution for follow-up during the active
monitoring phase (i.e., active treatment and clinical follow-up) of the study
- Willing to provide mandatory blood specimens for correlative research and banking
for future correlative research pertinent to this study
Exclusion Criteria:
- Any of the following:
- Pregnant persons
- Nursing persons (lactating persons are eligible provided that they agree not to
use their breast milk to feed while receiving treatment on the study or within
3 months of the last dose of study treatment)
- Men or women of reproductive potential who are unwilling to employ adequate
contraception during treatment and for 4 weeks after last dose of lenalidomide
or for 3 months after last dose of tafasitamab (whichever is longer)
- Any of the following prior therapies:
- Autologous stem cell transplant =< 90 days prior to registration
- Allogeneic stem cell transplant
- Anti-CD19 CAR T-cell therapy =< 90 days prior to registration
- Any central nervous system (CNS) involvement by MCL (e.g., any parenchymal,
leptomeningeal, cerebrospinal fluid [CSF], cranial or spinal nerve root involvement)
- Receiving any other treatment which would be considered as a treatment for MCL (with
the exception of corticosteroid). If a patient received recent MCL treatment prior
to registration, at least 5 half-lives of the drug(s) OR 14 days must have passed
following the last dose for the patient to be eligible
- Any of the following medication requirement or recent use:
- Anticoagulation with a vitamin K antagonist =< 7 days prior to registration
- Requirement of a P-gp inhibitor during the study
- Requirement of a strong cytochrome P450 (CYP) 3A inhibitor or inducer during
the study
- Use of a strong or moderate CYP3A inhibitor or inducer =< 7 days prior to
registration
NOTE: Because of their effect on CYP3A4, use of any of the following within 3 days of
registration or planned use during study participation is prohibited:
- Grapefruit or grapefruit products
- Seville oranges or products from Seville oranges
- Star fruit
- Human Immunodeficiency Virus (HIV) positive. All subjects will be screened for
HIV =< 14 days prior to registration
- Patient with chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring
treatment. All subjects will be screened for hepatitis B and hepatitis C =< 14
days prior to registration NOTE: Patients with positive hepatitis B surface
antigen (HBsAg) are excluded from participation in this trial. Patients with
positive hepatitis B core antibody (anti-HBc) and negative HBsAg require
hepatitis B polymerase chain reaction (PCR) evaluation. Patients who are
hepatitis B PCR positive will be excluded from participating in this trial
NOTE: Patients with positive hepatitis C antibody need to have a negative
result for hepatitis C ribonucleic acid (RNA). Patients who are hepatitis C RNA
positive will be excluded from participating in this trial
- Co-morbid systemic illnesses or other severe concurrent disease which, in the
judgment of the local investigator, would make the patient inappropriate for
entry into this study or interfere significantly with the proper assessment of
safety and toxicity of the prescribed regimens
- Uncontrolled intercurrent illness, in the judgement of the local investigator,
including, but not limited to:
- New York Heart Association (NYHA) class III or IV or symptomatic congestive heart
failure
- Unstable angina or acute coronary syndrome =< 3 months prior to registration
- Uncontrolled or symptomatic cardiac arrhythmia
- NOTE: Patients with pacemakers are eligible if they have no history of fainting
or clinically relevant arrhythmias while using the pacemaker
- Oxygen dependent baseline lung disease (such as interstitial lung disease or chronic
obstructive pulmonary disease [COPD])
- Ongoing inflammatory bowel disease (such as ulcerative colitis) requiring active
treatment
- Ongoing malabsorption syndrome or other condition that precludes enteral route of
administration
- Ongoing or active infection (viral, bacterial, or fungal)
- Psychiatric illness/social situations that would limit compliance with study
requirements
- History of the following:
- Cerebral vascular accident within 24 weeks prior to registration
- Myocardial infarction within 24 weeks prior to registration
- Major surgery =< 28 days prior to registration
- Live vaccination =< 28 days prior to registration
- Life-threatening thrombosis/embolism
- Bleeding diathesis that precludes the use of low-dose aspirin (81 mg daily) or any
form of anticoagulation
- Other active primary malignancy (other than localized non-melanotic skin cancer
or carcinoma in situ of the cervix) requiring treatment or limiting expected
survival to =< 2 years NOTE: If there is a history of prior malignancy, the
patient must be in remission not require ongoing therapy such as radiation,
chemotherapy or immunotherapy for their cancer. Patients on adjuvant hormonal
therapy for adequately treated nonmetastatic breast or prostate cancer are
permitted if they meet other eligibility criteria
- Unable to swallow oral drugs
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Mayo Clinic in Rochester
Address:
City:
Rochester
Zip:
55905
Country:
United States
Status:
Recruiting
Contact:
Last name:
ACCRU Operations
Phone:
507-538-6647
Email:
accru@mayo.edu
Investigator:
Last name:
Yucai Wang
Email:
Principal Investigator
Facility:
Name:
M D Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Not yet recruiting
Contact:
Last name:
Debbie Stroughter
Phone:
713-792-7734
Email:
CR_Study_Registration@mdanderson.org
Investigator:
Last name:
Michael Wang
Email:
Principal Investigator
Start date:
January 4, 2024
Completion date:
December 30, 2030
Lead sponsor:
Agency:
Academic and Community Cancer Research United
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
Academic and Community Cancer Research United
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05910801
