Trial Title:
Testing the Effectiveness of a Combination Targeted Therapy (ViPOR) for Patients With Relapsed and/or Refractory Aggressive B-cell Lymphoma
NCT ID:
NCT06649812
Condition:
High Grade B-Cell Lymphoma With MYC and BCL6 Rearrangements
Recurrent Diffuse Large B-Cell Lymphoma
Recurrent Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type
Recurrent Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
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 T-Cell/Histiocyte-Rich Large B-Cell Lymphoma
Refractory Diffuse Large B-Cell Lymphoma
Refractory Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type
Refractory Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
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 T-Cell/Histiocyte-Rich Large B-Cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Recurrence
Prednisone
Cortisone
Lenalidomide
Venetoclax
Obinutuzumab
Ibrutinib
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet 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 optional tumor biopsy
Arm group label:
Treatment (ViPOR)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (ViPOR)
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 and biopsy
Arm group label:
Treatment (ViPOR)
Intervention type:
Procedure
Intervention name:
Bone Marrow Biopsy
Description:
Undergo bone marrow aspiration and biopsy
Arm group label:
Treatment (ViPOR)
Other name:
Biopsy of Bone Marrow
Other name:
Biopsy, Bone Marrow
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Treatment (ViPOR)
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:
Computerized Tomography (CT) scan
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Ibrutinib
Description:
Given PO
Arm group label:
Treatment (ViPOR)
Other name:
BTK Inhibitor PCI-32765
Other name:
CRA 032765
Other name:
CRA-032765
Other name:
CRA032765
Other name:
Imbruvica
Other name:
PCI 32765
Other name:
PCI-32765
Other name:
PCI32765
Intervention type:
Drug
Intervention name:
Lenalidomide
Description:
Given PO
Arm group label:
Treatment (ViPOR)
Other name:
CC 5013
Other name:
CC-5013
Other name:
CC5013
Other name:
CDC 501
Other name:
Revlimid
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo MRI
Arm group label:
Treatment (ViPOR)
Other name:
Magnetic Resonance
Other name:
Magnetic Resonance Imaging (MRI)
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:
MRIs
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Other name:
sMRI
Other name:
Structural MRI
Intervention type:
Biological
Intervention name:
Obinutuzumab
Description:
Given IV
Arm group label:
Treatment (ViPOR)
Other name:
Anti-CD20 Monoclonal Antibody R7159
Other name:
GA 101
Other name:
GA-101
Other name:
GA101
Other name:
Gazyva
Other name:
huMAB(CD20)
Other name:
R 7159
Other name:
R-7159
Other name:
R7159
Other name:
RO 5072759
Other name:
RO-5072759
Other name:
RO5072759
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET
Arm group label:
Treatment (ViPOR)
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:
Drug
Intervention name:
Prednisone
Description:
Given PO
Arm group label:
Treatment (ViPOR)
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:
Drug
Intervention name:
Venetoclax
Description:
Given PO
Arm group label:
Treatment (ViPOR)
Other name:
ABT 199
Other name:
ABT-0199
Other name:
ABT-199
Other name:
ABT199
Other name:
GDC 0199
Other name:
GDC-0199
Other name:
GDC0199
Other name:
RG7601
Other name:
Venclexta
Other name:
Venclyxto
Summary:
This phase II trial tests how well venetoclax, ibrutinib, prednisone, obinutuzumab, and
Revlimid® (ViPOR) works in treating patients with CD10 negative diffuse large B-cell
lymphoma (DLBCL) and high-grade lymphoma with MYC and BCL2 rearrangements that has come
back after a period of improvement (relapsed) and/or that has not responded to previous
treatment (refractory). 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. Ibrutinib is in a class of medications called kinase
inhibitors. It blocks a protein called BTK, which is present on B-cell (a type of white
blood cells) cancers at abnormal levels. This may help keep cancer cells from growing and
spreading. Anti-inflammatory drugs, such as prednisone lower the body's immune response
and are used with other drugs in the treatment of some types of cancer. Obinutuzumab, a
monoclonal antibody, binds to a protein called CD20, which is found on B cells and some
types of leukemia and lymphoma cells. Obinutuzumab may block CD20 and help the immune
system kill cancer cells. Revlimid, a type of anti-angiogenesis agent and a type of
immunomodulating agent, may help the immune system kill abnormal blood cells or cancer
cells. It may also prevent the growth of new blood vessels that cancers need to grow.
ViPOR may be an effective treatment option for patients with relapsed and/or refractory
CD10 negative DLBCL and high-grade B-cell lymphoma with MYC and BCL2 rearrangements.
Detailed description:
PRIMARY OBJECTIVES:
I. To evaluate the complete response (CR) rate of ViPOR in relapsed/refractory (R/R):
Ia. CD10-negative DLBCL; and Ib. CD10-positive or negative high-grade B-cell lymphoma
(HGBCL) with MYC and BCL2 (with or without BCL6) translocations (HGBCL-double hit
[DH]-BCL2).
SECONDARY OBJECTIVES:
I. To evaluate the complete response (CR) rate of ViPOR in relapsed/refractory (R/R):
Ia. CD10-negative activated B-cell (ABC) DLBCL; and Ib. CD10-negative non-ABC (i.e.,
unclassified or germinal center B-cell [GCB]) DLBCL.
II. To evaluate the overall response rate (ORR), duration of response (DOR), event-free
survival (EFS), time to progression (TTP), progression-free survival (PFS), overall
survival (OS), and the safety & toxicity profile of ViPOR in relapsed/refractory (R/R):
IIa. CD10-negative ABC DLBCL; and IIb. CD10-negative non-ABC (i.e., unclassified or GCB)
DLBCL; and IIc. CD10-positive or negative HGBCL-DH-BCL2.
EXPLORATORY OBJECTIVES:
I. To assess response and outcome to ViPOR based on molecular DLBCL subtype by
cell-of-origin (COO) testing using Lymph2Cx gene-expression profiling (GEP).
II. To assess response and outcome to ViPOR based on genetic DLBCL subtype by LymphGen
classification using whole exome sequencing (WES), whole genome sequencing (WGS), and
ribonucleic acid (RNA)-sequencing (RNA-seq).
III. To determine other molecular correlates of response or resistance to ViPOR therapy.
IV. To determine early molecular correlates of response or resistance as well as the rate
of complete molecular remission, as determined by assays for circulating-tumor
deoxyribonucleic acid (DNA) (ctDNA).
OUTLINE:
Patients receive venetoclax orally (PO) once daily (QD) on days 2-14, ibrutinib PO QD on
days 1-14, prednisone PO QD on days 1-7, obinutuzumab intravenously (IV) on days 1 and 2,
and lenalidomide (Revlimid) PO QD on days 1-14 of each cycle. Cycles repeat every 21 days
for up to 6 cycles in the absence of disease progression or unacceptable toxicity.
Patients undergo blood sample collection, positron emission tomography (PET), computed
tomography (CT) and/or magnetic resonance imaging (MRI) and optional tumor biopsy and
bone marrow aspiration and biopsy throughout the study.
After completion of study treatment, patients are followed up every 6 months for 2 years,
yearly during years 3-5, and then for survival for up to 10 years from the date of
registration.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Patient must be ≥ 18 years of age
- Patient must have histologically or cytologically confirmed aggressive B-cell
lymphoma as follows:
- CD10-negative DLBCL, which includes:
- CD10-negative non-GCB DLBCL, not otherwise specified (NOS) (i.e.,
CD10-/BCL6- or CD10-/BCL6+/MUM1+ DLBCL)
- CD10-negative GCB DLBCL, NOS (i.e., CD10-/BCL6+/MUM1- DLBCL)
- CD10-negative HGBCL with MYC and BCL6 (without BCL2) translocations
(HGBCL-DH-BCL6)
- CD10-negative HGBCL, NOS (without MYC and BCL2 translocations)
- CD10-negative T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) OR
- CD10-positive or negative HGBCL with MYC and BCL2 rearrangements (with or
without BCL6 rearrangement) (HGBCL-DH-BCL2)
- NOTE: The site principal investigator must review and verify the pathology
report findings to ensure the patient is eligible and is assigned to the
respective cohort at the time of registration
- Patient must have relapsed and/or refractory disease after at least 1 prior
anthracycline and anti-CD20 antibody-containing regimen
- Patient must not have confirmed or suspected primary mediastinal large B-cell
lymphoma (PMBL)
- Patient must not be pregnant due to the potential harm to an unborn fetus with the
treatment regimens being used.
- All patients of childbearing potential must have a serum or urine study with a
sensitivity of at least 25 mIU/mL within 14 days prior to registration to rule
out pregnancy and again within 24 hours prior to starting cycle 1 day 1 of
treatment.
- A patient of childbearing potential is defined as anyone, regardless of sexual
orientation or whether they have undergone tubal ligation, who meets the
following criteria: 1) has achieved menarche at some point, 2) has not
undergone a hysterectomy or bilateral oophorectomy; or 3) has not been
naturally postmenopausal (amenorrhea following cancer therapy does not rule out
childbearing potential) for at least 24 consecutive months (i.e., has had
menses at any time in the preceding 24 consecutive months)
- Patients of childbearing potential must not expect to conceive children by
abstaining from sexual intercourse or by using accepted and effective methods of
contraception throughout the entire duration of protocol treatment, including during
dose interruptions, and for 6 months after the last dose of protocol treatment. Male
patients must not father children by abstaining from sexual intercourse or by using
a condom during sexual contact with pregnant partners or partners of childbearing
potential throughout the entire duration of protocol treatment, including dose
interruptions, and for 6 months after the last dose of protocol treatment even if
they have had a successful vasectomy
- Male patients must agree to not donate semen or sperm during the entire duration of
protocol treatment or for at least 28 days after the last dose of lenalidomide even
if they have had a successful vasectomy
- Patient must agree to abstain from breastfeeding during the entire duration of
protocol treatment and for at least 6 months after the last dose of protocol
treatment
- Patient must agree to abstain from donating blood during the entire duration of
protocol treatment and for at least 28 days after the last dose of lenalidomide
- Patient must have the ability to understand and the willingness to sign a written
informed consent document. Patients with impaired decision-making capacity (IDMC)
who have a legally authorized representative (LAR) or caregiver and/or family member
available will also be considered eligible
- Absolute neutrophil count (ANC) ≥ 1,000/mcL without requirement for granulocyte
colony stimulating factor (G-CSF) support (obtained ≤ 7 days prior to registration)
- Hemoglobin ≥ 8 g/dL (obtained ≤ 7 days prior to registration)
- Platelets ≥ 75,000/mcL without requirement for platelet transfusion support
(obtained ≤ 7 days prior to registration)
- Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (or ≤ 3.0 x
institutional ULN for patients with documented Gilberts syndrome) (obtained ≤ 7 days
prior to registration)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT])
≤ 3.0 x institutional ULN (obtained ≤ 7 days prior to registration)
- Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 30 mL/min/1.73 m^2 (estimated by
Cockcroft-Gault method or measured) (obtained ≤ 7 days prior to registration)
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months of registration are eligible
for this trial
- For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV
viral load must be undetectable on suppressive therapy, if indicated
- Patients with a history of hepatitis C virus (HCV) infection must have been treated
and cured. For patients with HCV infection who are currently on treatment, they are
eligible if they have an undetectable HCV viral load
- Patient must not have active central nervous system (CNS) lymphoma requiring
treatment
- Patients with treated brain metastases are eligible if follow-up brain imaging after
central nervous system (CNS)-directed therapy shows no evidence of progression
- Patients with a prior or concurrent malignancy whose natural history or treatment
does not have the potential to interfere with the safety or efficacy assessment of
the investigational regimen are eligible for this trial
- Patient must not have taken or require warfarin or other strong CYP3A inhibitors or
inducers within 7 days prior to registration.
- NOTE: Antiplatelet agents, other anticoagulants aside from warfarin, as well as
mild or moderate CYP3A inhibitors or inducers are permitted on study but should
be used with caution
- Patient must not have an uncontrolled intercurrent illness that would interfere with
the safety or efficacy assessment of this protocol
- Patient must not have evidence of an active infection at the time of registration
- Patient must not have the following current or prior anti-cancer treatment:
- Any chemotherapy, targeted therapy, or anti-cancer antibodies received within 2
weeks prior to registration
- NOTE: Short courses of corticosteroids or palliative external beam
radiation therapy (XRT) prior to registration are permitted
- More than 3 prior lines of cytotoxic chemotherapy, excluding targeted therapy,
anti-cancer antibodies, antibody-drug conjugates, and bi-specific antibodies
- NOTE: Cytoreductive chemotherapy followed by autologous stem cell
transplant (ASCT) counts as 1 line of cytotoxic therapy. Similarly,
cytoreductive chemotherapy (either pre-T-cell collection or as bridging
therapy) followed by pre-conditioning therapy/chimeric antigen receptor
T-cell (CAR-T) counts as 1 line of therapy, as long as no disease
progression occurs between interventions. For both therapies, if
progressive disease is documented between 2 distinct regimens, then they
should be counted as 2 lines of cytotoxic chemotherapy
- Radio- or toxin-immunoconjugates within 10 weeks prior to registration
- Previous treatment with more than one of the following study agents:
venetoclax, ibrutinib, or lenalidomide
- Prior autologous stem cell transplant (ASCT), chimeric antigen receptor T-cell
(CAR-T) therapy, or allogeneic stem cell (or other organ) transplant within 3
months prior to registration
- Any evidence of active graft-versus-host disease or requirement for
immunosuppressants within 28 days prior to registration
- NOTE: In addition, patient must have recovered (i.e., ≤ grade 1 or
baseline) from all adverse events due to previously administered
anti-cancer treatment, surgery, or procedure
- NOTE: Exceptions to this include events not considered to place the
patient at unacceptable risk of participation in the opinion of the
treating investigator (i.e., alopecia)
- Patients with known history or current symptoms of cardiac disease, or history of
treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac
function using the New York Heart Association Functional Classification. To be
eligible for this trial, patients should be class 2B or better
- Patient must have adequate formalin fixed paraffin embedded (FFPE) tumor tissue
specimen from the initial diagnostic biopsy or on-study repeat tumor tissue biopsy
for molecular analysis
- NOTE: Excisional tumor biopsy is preferred. Core needle biopsies will be
considered adequate if there is enough tissue for the mandatory molecular
analysis. Submission of an entire FFPE tumor block is preferred, but if
unavailable 10 x 10um FFPE scrolls may be submitted as an alternative. If
adequate archived FFPE tumor tissue is unavailable, the patient must be willing
to undergo research biopsy for molecular analysis
- Patient must have measurable disease
- Patient must have an Eastern Cooperative Oncology Group (ECOG) performance status
0-2
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
January 17, 2025
Completion date:
September 1, 2027
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Cancer Institute (NCI)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06649812
