Clinical trial for Refractory Diffuse Large B Cell Lymphoma (DLBCL)
Official title DALY II USA/ MB-CART2019.1 for DLBCL
ClinicalTrials.gov ID: NCT04792489
What this study is testing
What is zamtocabtagene autoleucel (MB-CART2019.1)?
This is an investigational cell therapy being studied as a potential treatment for certain types of B cell lymphoma. It is designed to use your own T cells, which are modified to recognize and target specific proteins (CD19 and CD20) on the surface of cancer cells.
Plain-language explanation of the investigational treatment. It is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- This study is testing how well a new cell therapy works. It also looks at how safe it is and what side effects it causes.
- Who it's for
- You may be able to join if you have a specific type of B-cell lymphoma that has returned or is hard to treat.
- What's involved
- You would receive a treatment made from your own cells. You would also have regular check-ups and blood tests.
- Time commitment
- The study involves several visits over time to track your health and the treatment's effects.
- Phase 2: a mid-size study of how well it works
- Time commitment: about 2 years
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 18 and older
You may be able to join if
- DLBCL cohort (both cohorts)
- DLBCL or associated subtype, defined by WHO 2016 classification
- DLBCL not otherwise specified (NOS)
- High-grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements
- High-grade B cell lymphoma (NOS)
You likely can't join if
- Primary CNS lymphoma (not applicable to CNS cohort)
- Richter's transformed DLBCL arising from chronic lymphocytic leukemia (CLL) (not applicable to RT cohort)
- Unable to give informed consent
- Known history of infection with human immunodeficiency virus (HIV) or active hepatitis B (HBsAg positive).
- Known history of infection with hepatitis C virus (anti-HCV positive) unless viral load is undetectable per quantitative PCR and/or nucleic acid...
- Pharmacologically uncontrolled seizures.
See the full eligibility criteria
Who can join
- DLBCL cohort (both cohorts)
- DLBCL or associated subtype, defined by WHO 2016 classification
- DLBCL not otherwise specified (NOS)
- High-grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements
- High-grade B cell lymphoma (NOS)
- Primary mediastinal (thymic) large B cell lymphoma
- Transformed lymphoma (e.g., transformed follicular, or marginal zone lymphoma, follicular lymphoma (FL Grade 3) o CNS cohort
- B-cell primary or secondary central nervous system lymphoma (PCNSL or SCNSL) o Mantle Cell Lymphoma (MCL) cohort
- Histologically confirmed MCL determined by overexpression of cyclin D1 or presence of t(11;14) (q13; q32) translocation o Richter's Transformation (RT) cohort
- Histologically confirmed RT to a diffuse large B-cell lymphoma (DLBCL) subtype from underlying CLL (clonally related)
- Relapsed or refractory disease is defined for DLBCL (and associated subtypes) population as: For DLBCL cohort (after receiving at least two prior lines of therapy): persistent disease after failure of 2 or more lines of...
- Chemotherapy-refractory disease (applies to all cohorts) is defined as persistent disease after last line of therapy or relapsed or persistent disease after prior ASCT for lymphoma
- Disease relapse in people without prior ASCT is defined as relapse of disease after the last dose of most recent therapy regimen For disease specific cohorts added after the initial DLBCL cohort the definition of...
- First-line therapy is defined as either high dose methotrexatebased therapy, temozolomide, high dose cytarabine, pemetrexed, lenalidomide or Bruton tyrosine kinase (BTK) inhibitor-based therapy.
- No contraindications for MRI evaluation
- CNS cohort: people with SCNSL must have relapsed or refractory disease after having received at least one prior line of systemic therapy
- Cytotoxic rituximab [or equivalent] based chemotherapy regimen (eg, rituximab bendamustine, R-CHOP, R-DHAP, R-ARA-C) AND
- BTK inhibitor RT cohort: Subject must have relapsed/refractory disease after at least one prior systemic treatment following Richter's Transformation DLBCL transplant ineligible 2nd cohort: subject must have failure of...
- Age ≥70 years
- ECOG status is 2 at screening
- Impaired pulmonary function: diffusing capacity of the lung for carbon monoxide [DLCO] ≤ 60% adjusted for gender-specific hemoglobin concentration (Coates formula)
- Impaired cardiac function: left ventricular ejection fraction (LVEF) \< 50%; must be assessed by echocardiogram or multiple uptake gated acquisition (MUGA) scan performed within 4 weeks of determination of eligibility
- Impaired renal function: calculated creatinine clearance (Cockcroft and Gault) \< 60 mL/min
- Age ≥18 years
- Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at screening. ECOG performance status of 2 at screen is allowed if the decrease in performance status is due to lymphoma
- people in DLBCL transplant-ineligible 2nd-line cohort with ECOG performance status of 2, regardless of attribution, will be allowed for inclusion
- Measurable disease will be assessed by FDG-PET/CT in systemic lymphoma . and by brain/spine MRI for CNS disease
- Subject must have a tumor biopsy sample (at least 16 unstained slides of tissue or tissue block) from the most recent relapse available prior to MB-CART2019.1 infusion.
- No clinical suspicion of central nervous system (CNS) lymphoma (not applicable to CNS cohort)
- people in DLBCL transplant-ineligible 2nd-line cohort with SCNSL will be allowed for inclusion
- If the subject has history of CNS disease (not applicable to CNS cohort), then he/she must have no signs or symptoms of CNS disease, have no active disease on magnetic resonance imaging (MRI), have no large cell...
- If has history of cerebral vascular accident (CVA), the CVA event must be greater than 12 months prior to leukapheresis. Any neurological deficits must be stable
- A creatinine clearance (as estimated by direct urine collection or Cockcroft-Gault Equation) \> 45mL/min
- Cardiac ejection fraction (EF) ≥ 45% as determined by an echocardiogram (ECHO) or Multigated Radionuclide Angiography (MUGA)
- people in DLBCL transplant-ineligible 2nd-line cohort with a lower ejection fraction of \> 40% will be allowed for inclusion
- Resting O2 saturation \>90% on room air
- Serum alanine aminotransferase (ALT) / aspartate aminotransferase (AST)\<5 times the Upper Limit of Normal (ULN) for age
- Total bilirubin \<1.5 mg/dl, except in individuals with Gilbert's syndrome
- people in DLBCL transplant-ineligible 2nd-line cohort with a total bilirubin of \< 2.0 mg/dL will be allowed for inclusion
- Absolute neutrophil count (ANC) \> 1000/μL
- Absolute lymphocyte count \> 100/μL
- Platelet count \> 50,000/µL
- Estimated life expectancy of more than 3 months other than primary disease
What rules you out
- Primary CNS lymphoma (not applicable to CNS cohort)
- Richter's transformed DLBCL arising from chronic lymphocytic leukemia (CLL) (not applicable to RT cohort)
- Unable to give informed consent
- Known history of infection with human immunodeficiency virus (HIV) or active hepatitis B (HBsAg positive).
- Known history of infection with hepatitis C virus (anti-HCV positive) unless viral load is undetectable per quantitative PCR and/or nucleic acid testing.
- Pharmacologically uncontrolled seizures.
- Known history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis, or other immunologic or inflammatory disease
- For CNSL and DLBCL transplant-ineligible 2nd-line cohort patients that have a CNS lesion(s): Midline shift on MRI or Abnormal high CSF opening pressure and or CSF protein ≥150 mg/dL Recent (within 3 months) whole brain...
- Active systemic fungal, viral, or bacterial infection
- Pregnant or breast-feeding woman
- Adequately treated basal cell or squamous cell carcinoma (adequate wound healing required prior to study entry)
- In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 2 years prior to the study
- Adequately treated breast or prostate carcinoma on hormonal therapies such as Lupron or tamoxifen and in clinical remission of ≥ 2 years
- A primary malignancy which has been completely resected / treated with curative intent and in complete remission of ≥ 2 years
- Severely immunocompromised people e.g., due to current treatment of non-neurologic autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus).
- Medical condition requiring prolonged use of systemic corticosteroids equivalent to prednisone \>10 mg/day.
- History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months of enrollment.
- Concurrent radiotherapy (allowed up to time of lymphodepletion). For prior systemic therapy, at least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed at the time of scheduled leukapheresis.
- Baseline dementia that would interfere with therapy or monitoring, determined using Immune Effector Cell-Associated Encephalopathy (ICE) Assessment at baseline.
- History of severe immediate hypersensitivity reaction to any of the agents used in this study.
- Refusal to participate in additional lentiviral gene therapy long-term follow-up (LTFU) protocol
- Prior CAR-T therapy for any indication or systemic gene modifying therapy for B-cell lymphoma
- Prior allogeneic stem cell transplant for any indication
- Prior Bispecific T cell engaging (BITE) antibodies for cancer therapy
- Prior T cell receptor-engineered T cell therapy
The study team makes the final eligibility decision.
Where it is enrolling
- Birmingham, Alabama, United States
- Gilbert, Arizona, United States
- Phoenix, Arizona, United States
- La Jolla, California, United States
- Stanford, California, United States
- Denver, Colorado, United States
- New Haven, Connecticut, United States
- Miami, Florida, United States
- Atlanta, Georgia, United States
- Augusta, Georgia, United States
- Chicago, Illinois, United States
- Westwood, Kansas, United States
- Baltimore, Maryland, United States
- Boston, Massachusetts, United States
- Ann Arbor, Michigan, United States
- Rochester, Minnesota, United States
- St Louis, Missouri, United States
- New York, New York, United States
- Durham, North Carolina, United States
- Columbus, Ohio, United States
+ 10 more site(s).
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part, but confirm specifics with the study team.
How long does this study last?
The study runs about 2 years per participant, based on its public description. The team confirms the exact schedule and number of visits before you enroll.
Who can join this trial?
This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.
Where is this trial taking place?
This study is enrolling now at Birmingham, Alabama, United States; Gilbert, Arizona, United States; Phoenix, Arizona, United States; La Jolla, California, United States; Stanford, California, United States; Denver, Colorado, United States and 24 more locations. Enter your location above to see the nearest enrolling site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool that is independent of the study sponsor. Details come from ClinicalTrials.gov. The study team decides eligibility, and your own doctor gives medical advice.