Recruiting PHASE2 Refractory Diffuse Large B Cell Lymphoma (DLBCL)

New treatment option 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)?

zamtocabtagene autoleucel (MB-CART2019.1) is an investigational medicine, given as an infusion into a vein, being studied as a potential treatment for refractory diffuse large b cell lymphoma (dlbcl).

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: DALY II USA is a phase II, multi-center, single arm study to evaluate the efficacy, safety, and pharmacokinetics of zamtocabtagene autoleucel (MB-CART2019.1) in patients with relapsed and/or refractory B cell lymphoma (BCL). Cohorts include subjects with diffuse large B-cell lymphoma (DLBCL) after receiving at least 2 lines of therapy, primary or secondary central nervous system (CNS) lymphoma (PCNSL) and (SCNSL) after receiving at least one line of therapy, mantle cell lymphoma (MCL) and Richter's transformation (RT) after receiving at least one line of therapy, and DLBCL transplant-ineligible after receiving at least one line of therapy.

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

Histologically confirmed B-cell non-Hodgkin's lymphoma:
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

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). If there is a history of treated hepatitis...
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

Histologically confirmed B-cell non-Hodgkin's lymphoma:
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
Prior lines of systemic therapy should include an anti-CD20 monoclonal antibody and anthracycline containing chemotherapy regimen and/or with or without an autologous stem cell transplant MCL cohort: people with...
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...
For this cohort people are considered transplant ineligible if they meet one of the following criteria:
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
Impaired hepatic function: aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \> 2 x upper limit of normal (ULN) In addition, all people must have:
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. If medically not feasible to obtain a biopsy from...
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). If there is a history of treated hepatitis B or hepatitis C, the viral load must be quantitative polymerase...
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
Presence of CNS disorder that, in the judgment of the Investigator, may impair the ability to evaluate neurotoxicity. For CNS Cohort:
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
Previous or concurrent malignancy with the following exceptions:
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. For CNS cohort: Up to 2 mg/day dexamethasone (or equivalence) may be allowed at any time, higher doses allowed...
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's taking place

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
Omaha, Nebraska, United States
New York, New York, United States
Durham, North Carolina, United States

+ 11 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 - 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?

Study sites include 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 25 more location(s). Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.