Trial Title:
Acalabrutinib + Liso-Cel In R/R Aggressive B-Cell Lymphomas
NCT ID:
NCT05583149
Condition:
Refractory Aggressive B-cell Lymphomas
Refractory B-Cell Non-Hodgkin Lymphoma
Aggressive B-cell NHL
Diffuse Large B-cell Lymphoma (DLBCL)
De Novo or Transformed Indolent B-cell Lymphoma
DLBCL, Nos Genetic Subtypes
T Cell/Histiocyte-rich Large B-cell Lymphoma
EBV-Positive DLBCL, Nos
Primary Mediastinal [Thymic] Large B-cell Lymphoma (PMBCL)
High-Grade B-Cell Lymphoma, Nos
C-MYC/BCL6 Double-Hit High-Grade B-Cell Lymphoma
Grade 3b Follicular Lymphoma
C-MYC/BCL2 Double-Hit High-Grade B-Cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Aggression
Cyclophosphamide
Fludarabine
Acalabrutinib
Conditions: Keywords:
Refractory aggressive B-cell lymphomas
Refractory B-Cell Non-Hodgkin Lymphoma
Aggressive B-cell NHL
Diffuse Large B-cell Lymphoma (DLBCL)
De novo or transformed indolent B-cell lymphoma
DLBCL, nos Genetic Subtypes
T cell/histiocyte-rich large B-cell lymphoma
EBV-Positive DLBCL, nos
Primary mediastinal [thymic] large B-cell lymphoma (PMBCL)
High-Grade B-Cell Lymphoma, nos
C-MYC/BCL6 Double-Hit High-Grade B-Cell Lymphoma
Grade 3b Follicular Lymphoma
C-MYC/BCL2 Double-Hit High-Grade B-Cell Lymphoma
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:
ACALABRUTINIB
Description:
Oral, twice daily, timing and dosage per protocol
Arm group label:
ACALABRUTINIB and LISOCABTAGENE MARALEUCEL
Other name:
Calquence
Intervention type:
Drug
Intervention name:
LISOCABTAGENE MARALEUCEL
Description:
via IV timings and dosage per protocol
Arm group label:
ACALABRUTINIB and LISOCABTAGENE MARALEUCEL
Other name:
Breyanzi
Intervention type:
Drug
Intervention name:
Lymphodepleting chemotherapy
Description:
lymphodepleting chemotherapy with cyclophosphamide and fludarabine once a day for 3 days
via IV about 2-4 hours. This will occur only once prior to lisocabtagene maraleucel
infusion.
Arm group label:
ACALABRUTINIB and LISOCABTAGENE MARALEUCEL
Other name:
cyclophosphamide and fludarabine
Summary:
This research is being done to assess the effectiveness and safety of acalabrutinib
combined with lisocabtagene maraleucel (liso-cel) for people with relapsed/refractory
aggressive B-cell lymphoma.
This research study involves the study drug acalabrutinib in combination with
lisocabtagene maraleuce
Detailed description:
This research study involves the study drug acalabrutinib in combination with
lisocabtagene maraleucel.
The research study procedures include screening for eligibility and study treatment
including evaluations and follow up visits.
- Participants will receive one infusion of liso-cel and will receive acalabrutinib
capsules twice daily as long as treatment is tolerated and disease does not worsen
(disease progression) for up to one year.
Participants will be followed by clinical visits for up to 5 years and the medical record
will be monitored for up to 15 years.
It is expected that about 27 people will take part in this research study.
This research study is a Phase II clinical trial. Phase II clinical trials test the
safety and effectiveness of an investigational intervention to learn whether the
intervention works in treating a specific disease. "Investigational" means that the
intervention is being studied.
The U.S. Food and Drug Administration (FDA) has not approved acalabrutinib for this
specific disease, but it has been approved for other uses.
The U.S. FDA has approved lisocabtagene maraleucel for this specific disease.
AstraZeneca, a pharmaceutical company, is supporting this research study by providing
funding for the research study and supplying acalabrutinib.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Adult patients ≥18 years with histologically confirmed aggressive B-cell NHL
including diffuse large B-cell lymphoma (DLBCL), either de novo or transformed from
any indolent B-cell lymphoma, and including DLBCL NOS, T cell/histiocyte-rich large
B-cell lymphoma, Epstein-Barr virus [EBV] positive DLBCL NOS, primary mediastinal
[thymic] large B-cell lymphoma (PMBCL), high grade B-cell lymphoma NOS, or high
grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements [double/triple
hit lymphoma (DHL/THL)]; and grade 3B follicular lymphoma. Patients with primary CNS
lymphoma are not eligible. Patients with secondary CNS involvement by lymphoma are
eligible if they otherwise meet all eligibility criteria.
- Relapsed or refractory to at least 2 prior lines of systemic lymphoma therapy.
Previous therapy must have included a CD20-targeted agent and an anthracycline or
alkylating agent.
- PET-positive measurable disease
- ECOG Performance status 0-2
- Estimated creatinine clearance of ≥30 mL/min, calculated using the Cockcroft and
Gault equation (if male, [140Age] x Mass [kg] / [72 x creatinine g/dL];multiply by
0.85 if female)
- Alanine Aminotransferase (ALT) <= 2.5 times the ULN
- Bilirubin <= 2 x ULN (or <= 3.0 mg/dL for patients with Gilbert-Meulengracht
syndrome or lymphomatous involvement of the liver)
- Hemodynamically stable and Left Ventricle Ejection Fraction (LVEF) >= 40% confirmed
by echocardiogram or Multigated Radionuclide Angiography (MUGA)
- For subjects with atrial fibrillation, atrial fibrillation must be controlled and
asymptomatic
- Absolute neutrophil count (ANC) >= 1000/mm3
- Platelets >= 50,000/mm3
- Adequate pulmonary function, defined as <= CTCAE Grade 1 dyspnea and SaO2 > 91% on
room air
- Adequate vascular access for leukapheresis procedure (either peripheral line or
surgically-placed line)
- Woman of childbearing potential (WOCBP) who are sexually active must use highly
effective methods of contraception during treatment and for 2 days after the last
dose of acalabrutinib.
- Willing and able to participate in all required evaluations and procedures in this
study protocol.
- Ability to understand the purpose and risks of the study and provide signed and
dated informed consent and authorization to use protected health information.
Exclusion Criteria:
- Another active malignancy which requires concurrent cancer-directed therapy
- Previous treatment with gene therapy product or adoptive T cell therapy
- Allogeneic stem cell transplant within 90 days of leukapheresis
- Active acute or chronic GVHD
- HIV infection
- Serologic status reflecting active hepatitis B or C infection
- Subjects who are hepatitis B core antibody (anti-HBc) positive and who are
hepatitis B surface antigen (HBsAg) negative will need to have a negative PCR
result before enrollment and must be willing to undergo DNA PCR testing during
the study. Those who are HbsAg-positive or hepatitis B PCR positive will be
excluded.
- Subjects who are hepatitis C antibody positive will need to have a negative PCR
result before enrollment. Those who are hepatitis C PCR positive will be
excluded.
- Uncontrolled infection
- Clinically relevant CNS pathology
- History of cardiovascular conditions within the past 6 months, including class III
or IV heart failure as defined by New York Heart Association (NYHA), cardiac
angioplasty or stenting, myocardial infarction, unstable angina, or clinically
significant arrhythmias: Participants 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, participants should be
class 2B or better.
- Autoimmune disease requiring chronic systemic corticosteroids at a dose of greater
than 10 mg of prednisone daily or an equivalent dose of another corticosteroid
- Treatment with alemtuzumab within 6 months leukapheresis or fludarabine or
cladribine within 3 months of leukapheresis
- Therapeutic anticoagulation
- Bleeding diathesis
- Has difficulty with or is unable to swallow oral medication, or has significant
gastrointestinal disease that would limit absorption of oral medication.
- Known history of hypersensitivity or anaphylaxis to study drug(s) including active
product or excipient components.
- Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before
screening.
- Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer.
- Prothrombin time (PT)/INR or aPTT (in the absence of lupus anticoagulant) >2x ULN.
- Requires treatment with proton pump inhibitors (eg, omeprazole, esomeprazole,
lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Note: Subjects
receiving proton pump inhibitors who switch to H2-receptor antagonists or antacids
are eligible for enrollment to this study.
- History of significant cerebrovascular disease/event, including stroke or
intracranial hemorrhage, within 6 months before the first dose of study drug.
- Major surgical procedure within 28 days of first dose of study drug. Note: If a
subject had major surgery, they must have recovered adequately from any toxicity
and/or complications from the intervention before the first dose of study drug.
- Breastfeeding or pregnant: Pregnant women are excluded from this study because
acalabrutinib is an agent with the potential for teratogenic or abortifacient
effects.
Because there is an unknown but potential risk for adverse events in nursing infants
secondary to treatment of the mother with acalabrutinib, breastfeeding should be
discontinued if the mother is treated with acalabrutinib.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Massachusetts General Hospital
Address:
City:
Boston
Zip:
02115
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jeremy Abramson, MD
Phone:
617-724-4000
Investigator:
Last name:
Jeremy Abramson, MD
Email:
Principal Investigator
Facility:
Name:
Beth-Israel Deaconess Medical Center
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jon Arnason, MD
Phone:
617-667-9920
Investigator:
Last name:
Jon Arnason, MD
Email:
Principal Investigator
Start date:
March 1, 2023
Completion date:
March 1, 2029
Lead sponsor:
Agency:
Patrick C. Johnson, MD
Agency class:
Other
Collaborator:
Agency:
AstraZeneca
Agency class:
Industry
Source:
Massachusetts General Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05583149
