RECRUITING

DALY II USA/ MB-CART2019.1 for DLBCL

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Conditions

Refractory Diffuse Large B Cell Lymphoma (DLBCL)Relapsed Diffuse Large B Cell LymphomaHigh Grade B-cell Lymphoma (HGBCL)Primary Mediastinal B-cell Lymphoma (PMBCL)Transformed LymphomaCentral Nervous System LymphomaMantle Cell Lymphoma (MCL)Richter's TransformationCD19/CD20-directed CAR-T CellsZamtocabtagene autoleucelB-Cell Non-Hodgkin LymphomaPrimary Central Nervous System LymphomaSecondary Central Nervous System LymphomaNHLPCNSLSCNSLChimeric Antigen ReceptorCARCAR-T CellAutologous T Cell TherapyCentral Nervous System NeoplasmsLymphomaLymphoma, Non-HodgkinLymphoma, B-CellLymphoma, Large B-Cell, DiffuseMCLRTCLLImmunotherapyT cellsT cell infusion

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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 diffuse large B cell lymphoma (DLBCL) after receiving at least two lines of therapy. Additional cohorts include subjects with B-cell primary or secondary central nervous system (CNS) lymphoma (PCNSL) and (SCNSL), mantle cell lymphoma (MCL) and Richter's transformation (RT) after receiving at least one line of therapy.

Official Title

A Multi-center Single Arm Phase II Study to Evaluate the Safety and Efficacy of Genetically Engineered Autologous Cells Expressing Anti-CD20 and Anti-CD19 Specific Chimeric Antigen Receptor in Subjects With Relapsed and/or Refractory Diffuse Large B Cell Lymphoma

Quick Facts

Study Start:2021-05-25
Study Completion:2028-12-31
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT04792489

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * Histologically confirmed B-cell non-Hodgkin's lymphoma:
  2. * DLBCL DLBCL or associated subtype, defined by WHO 2016 classification:
  3. * DLBCL not otherwise specified (NOS)
  4. * High-grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements
  5. * High-grade B cell lymphoma (NOS)
  6. * Primary mediastinal (thymic) large B cell lymphoma
  7. * Transformed lymphoma (e.g., transformed follicular, or marginal zone lymphoma, follicular lymphoma (FL Grade 3)
  8. * CNS Cohort only: B-cell primary or secondary central nervous system lymphoma (PCNSL or SCNSL)
  9. * Mantle Cell Lymphoma (MCL) Cohort: Histologically confirmed MCL determined by overexpression of cyclin D1 or presence of t(11;14) (q13; q32) translocation
  10. * Richter's Transformation (RT) Cohort: Histologically confirmed Richter's transformation (RT) to a diffuse large B-cell lymphoma (DLBCL) subtype from underlying CLL (clonally related)
  11. * Relapsed or refractory disease is defined for DLBCL (and associated subtypes) population as failure of 2 or more lines of chemotherapy including rituximab or equivalent and anthracycline and either having failed autologous stem cell transplant (ASCT), or ineligible, not intended for or not consenting to ASCT
  12. * Chemotherapy-refractory disease is defined as persistent disease after last line of therapy or relapsed or persistent disease after prior ASCT for lymphoma
  13. * Disease relapse in subjects without prior ASCT is defined as relapse of disease after the last dose of most recent therapy regimen
  14. * CNS Cohort: Subjects with relapsed/refractory PCNSL that have failed (or unable to tolerate) at least first-line therapy.
  15. * No contraindications for MRI evaluation
  16. * CNS Cohort: Subjects with SCNSL must have relapsed or refractory disease after having received at least one prior line of systemic therapy
  17. * 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
  18. * No contraindications for MRI evaluation
  19. * MCL Cohort: Subjects with relapsed/refractory disease after at least one prior systemic treatment, that must include:
  20. * Cytotoxic rituximab-based chemotherapy regimen (eg, rituximab bendamustine, R-CHOP, R-DHAP, R-ARA-C) AND
  21. * BTK inhibitor
  22. * RT Cohort: Subject must have relapsed/refractory disease after at least one prior systemic treatment following Richter's Transformation
  23. * Age ≥18 years
  24. * 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
  25. * Measurable disease according to Lugano 2014 criteria for assessing FDG-PET/CT in systemic lymphoma (Cheson et al, 2014). Measurable disease according to IPCG criteria will be assessed by brain/spine MRI for CNS disease
  26. * 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 the most recent relapse and for cases when the amount of tissue is limited, the sponsor should be consulted, to confirm adequacy of the sample for study required analyses
  27. * No clinical suspicion of central nervous system (CNS) lymphoma (not applicable to CNS cohort)
  28. * 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 lymphoma present in cerebral spinal fluid (CSF), regardless of the number of white blood cells (WBCs)
  29. * 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
  30. * A creatinine clearance (as estimated by direct urine collection or Cockcroft-Gault Equation) \> 45mL/min
  31. * Cardiac ejection fraction (EF) ≥ 45% as determined by an echocardiogram (ECHO) or Multigated Radionuclide Angiography (MUGA)
  32. * Resting O2 saturation \>90% on room air
  33. * Serum alanine aminotransferase (ALT) / aspartate aminotransferase (AST)\<5 times the Upper Limit of Normal (ULN) for age
  34. * Total bilirubin \<1.5 mg/dl, except in individuals with Gilbert's syndrome
  35. * Absolute neutrophil count (ANC) \> 1000/μL
  36. * Absolute lymphocyte count \> 100/μL
  37. * Platelet count \> 50,000/µL
  38. * Estimated life expectancy of more than 3 months other than primary disease
  1. * Primary CNS lymphoma (not applicable to CNS cohort)
  2. * Richter's transformed DLBCL arising from chronic lymphocytic leukemia (CLL) (not applicable to RT cohort)
  3. * Unable to give informed consent
  4. * 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 chain reaction (PCR) negative; antiviral prophylaxis is required if HBsAg negative and anti-HBc positive
  5. * Known history of infection with hepatitis C virus (anti-HCV positive) unless viral load is undetectable per quantitative PCR and/or nucleic acid testing.
  6. * Pharmacologically uncontrolled seizures.
  7. * Known history or presence of autoimmune CNS disease, such as multiple sclerosis, optic neuritis, or other immunologic or inflammatory disease
  8. * Presence of CNS disorder that, in the judgment of the investigator, may impair the ability to evaluate neurotoxicity. For CNS Cohort:
  9. * Midline shift on MRI
  10. * Abnormal high CSF opening pressure and or CSF protein \>150 mg/dL Recent (within 3 months) whole brain radiotherapy (WBRT)
  11. * Active systemic fungal, viral, or bacterial infection
  12. * Pregnant or breast-feeding woman
  13. * Previous or concurrent malignancy with the following exceptions:
  14. * Adequately treated basal cell or squamous cell carcinoma (adequate wound healing required prior to study entry)
  15. * In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 2 years prior to the study
  16. * Adequately treated breast or prostate carcinoma on hormonal therapies such as Lupron or tamoxifen and in clinical remission of ≥ 2 years
  17. * A primary malignancy which has been completely resected / treated with curative intent and in complete remission of ≥ 2 years
  18. * Severely immunocompromised subjects e.g., due to current treatment of non-neurologic autoimmune disease (e.g., Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus).
  19. * 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 up to 7 days prior to apheresis or after apheresis until lymphodepletion.
  20. * History of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 6 months of enrollment
  21. * Concurrent radiotherapy (normal tissue sparing palliative radiotherapy allowed up to time of lymphodepletion). For systemic therapy, at least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed at the time of scheduled leukapheresis.
  22. * Baseline dementia that would interfere with therapy or monitoring, determined using Immune Effector Cell-Associated Encephalopathy (ICE) Assessment at baseline
  23. * History of severe immediate hypersensitivity reaction to any of the agents used in this study
  24. * Refusal to participate in additional lentiviral gene therapy LTFU protocol
  25. * Prior CAR-T therapy for any indication or systemic gene modifying therapy for B-cell lymphoma
  26. * Prior allogeneic stem cell transplant for any indication
  27. * Prior BITE antibodies for cancer therapy
  28. * Prior T cell receptor-engineered T cell therapy

Contacts and Locations

Study Contact

Bryan Dumont
CONTACT
617-218-0044
clinicaltrials@miltenyi.com
Harshita Gahankari
CONTACT
617-218-0044
clinicaltrials@miltenyi.com

Principal Investigator

Johanna Theruvath, MD
STUDY_DIRECTOR
Miltenyi Biomedicine GmbH

Study Locations (Sites)

Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234
United States
Mayo Clinic
Phoenix, Arizona, 85054
United States
UC San Diego Health
La Jolla, California, 92037
United States
Stanford University
Stanford, California, 94305
United States
Yale University
New Haven, Connecticut, 06520
United States
Baptist Health Miami Cancer Institute
Miami, Florida, 33176
United States
Winship Cancer Institute of Emory University
Atlanta, Georgia, 30322
United States
Georgia Cancer Center at Augusta University
Augusta, Georgia, 30912
United States
Robert H Lurie Cancer Center
Chicago, Illinois, 60611
United States
University of Kansas Cancer Center
Westwood, Kansas, 66205
United States
University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center
Baltimore, Maryland, 21201
United States
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
United States
University of Michigan
Ann Arbor, Michigan, 48109
United States
Mayo Clinic
Rochester, Minnesota, 55905
United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198
United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
United States
Duke University Medical Center - Division of Hematologic Malignancies
Durham, North Carolina, 27705
United States
The Ohio State University Wexner Medical Center James Cancer
Columbus, Ohio, 43210
United States
Oregon Health and Science University Knight Cancer Institute
Portland, Oregon, 97239
United States
University of Pittsburgh - Hillman Cancer Center
Pittsburgh, Pennsylvania, 15260
United States
Allegheny Health Network Cancer Institute
Pittsburg, Pennsylvania, 15212
United States
UT Southwestern Medical Center
Dallas, Texas, 75390
United States
Froedtert Hospital and the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
United States

Collaborators and Investigators

Sponsor: Miltenyi Biomedicine GmbH

  • Johanna Theruvath, MD, STUDY_DIRECTOR, Miltenyi Biomedicine GmbH

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-05-25
Study Completion Date2028-12-31

Study Record Updates

Study Start Date2021-05-25
Study Completion Date2028-12-31

Terms related to this study

Keywords Provided by Researchers

  • CD19/CD20-directed CAR-T Cells
  • Zamtocabtagene autoleucel
  • B-Cell Non-Hodgkin Lymphoma
  • Primary Central Nervous System Lymphoma
  • Secondary Central Nervous System Lymphoma
  • NHL
  • PCNSL
  • SCNSL
  • Chimeric Antigen Receptor
  • CAR
  • CAR-T Cell
  • Autologous T Cell Therapy
  • Central Nervous System Neoplasms
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell
  • Lymphoma, Large B-Cell, Diffuse
  • MCL
  • RT
  • CLL
  • Immunotherapy
  • T cells
  • T cell infusion

Additional Relevant MeSH Terms

  • Refractory Diffuse Large B Cell Lymphoma (DLBCL)
  • Relapsed Diffuse Large B Cell Lymphoma
  • High Grade B-cell Lymphoma (HGBCL)
  • Primary Mediastinal B-cell Lymphoma (PMBCL)
  • Transformed Lymphoma
  • Central Nervous System Lymphoma
  • Mantle Cell Lymphoma (MCL)
  • Richter&#39;s Transformation