A Study to Evaluate CTX110 in Subjects with Relapsed or Refractory B-Cell Malignancies

Overview

About this study

The purpose of this study is to evaluate the safety and effectiveness CTX110 in subjects with relapsed or refractory B cell malignancies.

 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria (For all cohorts, unless otherwise specified):

  • Age ≥ 18 years (Cohorts A, B, C, E, and F), or ≥ 18 to ≤ 70 years (Cohort D).
  • Able to understand and comply with protocol-required study procedures and voluntarily sign a written informed consent document.
  • Diagnosed with 1 of the following B cell malignancies:
    • Cohorts A, B, C, E, and F: Histologically confirmed B cell NHLs: DLBCL NOS, high grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, transformed FL, or grade 3b FL;
    • Confirmation of tumor histology from local pathology lab (archival tissue from last relapse/ progression [within 3 months of enrollment] or biopsy during screening);
    • At least 1 measurable lesion that is FDG PET–positive, as defined by Lugano criteria (Deauville score of 4 or 5 on Lugano criteria 5-point scale).
    • Note: Previously irradiated lesions will be considered measurable only if progression is documented following completion of radiation therapy.
    • Cohort D: Histologically confirmed B cell ALL:
      • D1: Bone marrow involvement with ≥ 5% blasts (see investigational plan in the protocol body);
      • D2: Bone marrow MRD-positive (defined as > 1 × 10-4 cells detected by flow cytometry or polymerase chain reaction [PCR]) with ≤ 5% blasts.
  • Refractory or relapsed disease, as evidenced by the following cohort-specific Cohorts A, B, C, E, and F (NHL):
    • 2 or more lines of prior therapy, including an antiCD20 monoclonal antibody and an anthracycline-containing regimen, AND have failed prior autologous hematopoietic stem cell transplantation (HSCT) OR ineligible for or refused prior autologous HSCT. Subjects who have received autologous HSCT must have recovered from HSCT-related toxicities;
    • For refractory disease, subjects must have PD on last therapy, or have SD following at least 2 cycles of therapy, with duration of SD of up to 6 months;
    • For subjects with transformed FL, subjects must have received at least 1 line of chemotherapy for disease after transformation to DLBCL.
  • Cohort D (adult B cell ALL):
    • 2 or more lines of prior therapy; or
    • Any bone marrow relapse after allogeneic HSCT; or
    • Philadelphia chromosome - positive (Ph+) if subjects are intolerant to or ineligible for tyrosine kinase inhibitor (TKI) therapy, or have progressed after at least 1 line of TKI therapy:
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
  • Meets criteria to undergo LD chemotherapy and CAR T cell infusion (all cohorts) and daratumumab infusion (Cohort C only).
  • Adequate organ function:
  • Renal
    • Estimated glomerular filtration rate > 50 mL/min/1.73 m^2;
  • Liver
    • Aspartate transaminase or alanine transaminase < 3 x upper limit of normal (ULN); total bilirubin > < 5 x ULN (for subjects with Gilbert’s syndrome, total bilirubin > < 2 mg/dL).
  • Cardiac
    • Hemodynamically stable and left ventricle ejection fraction ≥ 45% by echocardiogram;
    • Pulmonary: Oxygen saturation level on room air > 91% per pulse oximetry.
  • Female subjects of childbearing potential (postmenarcheal with an intact uterus and at least 1 ovary, who are less than 1 year postmenopausal) must agree to use acceptable method(s) of contraception from enrollment through at least 12 months after CTX110 infusion.
  • Male subjects must agree to use effective contraception from enrollment through at least 12 months after CTX110 infusion.
  • Agree to participate in an additional long-term follow-up study after completion of this study.

Exclusion Criteria (For all cohorts, unless otherwise specified):

  • Eligible for and agrees to autologous HSCT.
  • Treatment with the following therapies as described below:
    • Prior treatment with any gene therapy or genetically modified cell therapy, including CAR T cells;
    • Prior treatment with a CD19-directed antibody, bispecific T cell engager, or antibody-drug conjugate, unless there is confirmed CD19 expression (by immunohistochemistry or flow cytometry) after progression or relapse following most recent CD19-directed treatment.
  • Prior allogeneic HSCT. For subjects with B cell ALL, prior allogeneic HSCT is permissible if it has been more than 6 months from HSCT at the time of screening; there is no evidence of acute or chronic GvHD; and the subject has recovered from HSCT-related toxicities, has been off immunosuppressive therapies for at least 3 months prior to screening, and has not received donor lymphocyte infusion for at least 2 months prior to screening.
  • Known contraindication to daratumumab (Cohort C only), cyclophosphamide, fludarabine, or any of the excipients of CTX110 product.
  • Detectable malignant cells from cerebrospinal fluid (CSF) or magnetic resonance imaging (MRI) indicating brain metastases during screening, or a history of central nervous system (CNS) involvement by malignancy (CSF or imaging).
  • History of a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement.
  • Unstable angina, clinically significant arrhythmia, or myocardial infarction within 6 months of enrollment.
  • 8. Presence of bacterial, viral, or fungal infection that is uncontrolled or requires IV anti-infectives
  • Positive for presence of human immunodeficiency virus (HIV) type 1 or 2, or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Subjects with prior history of HBV or HBC infection who have documented undetectable viral load (by quantitative polymerase chain reaction [PCR] or nucleic acid testing) are permitted. Infectious disease testing (HIV-1, HIV-2, HCV antibody and PCR, HBV surface antigen, HBV surface antibody, HBV core antibody) performed within 30 days of signing the informed consent form may be considered for subject eligibility.
  • Previous or concurrent malignancy, except basal cell or squamous cell skin carcinoma, adequately resected and in situ carcinoma of cervix, or a previous malignancy that was completely resected and has been in remission for ≥ 5 years.
  • Radiation therapy within 14 days of enrollment.
  • Use of systemic antitumor therapy or investigational agent within 14 days or 5 half-lives, whichever is longer, of enrollment. Exceptions are made for:
    • prior inhibitory/stimulatory immune checkpoint molecule therapy, which is prohibited within 3 half-lives of enrollment; and
    • rituximab use within 30 days prior to screening is prohibited.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Hemant Murthy, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

International patient clinical studies questions