Clinical Trials /

A Study of CC-97540, CD19-targeted NEX-T Chimeric Antigen Receptor (CAR) T Cells, in Subjects With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

NCT04231747

Description:

This is a Phase 1, first-in-human, open-label, multicenter study of CC-97540, CD19-targeted NEX-T chimeric antigen receptor (CAR) T cells, in subjects with relapsed or refractory B-cell non-Hodgkin lymphoma. The study will consist of 2 parts: dose-escalation (Part A) and dose-expansion (Part B). The dose-escalation part (Part A) of the study is to evaluate the safety and tolerability of increasing dose levels of CC-97540 to establish a recommended Phase 2 dose (RP2D); and the dose-expansion part (Part B) of the study is to further evaluate the safety, pharmacokinetics/pharmacodynamics, and efficacy of CC-97540 at the RP2D.

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
  • Diffuse Large B-Cell Lymphoma, Not Otherwise Specified
  • Double-Hit Lymphoma
  • Grade 3b Follicular Lymphoma
  • Marginal Zone Lymphoma
  • Primary Mediastinal B-Cell Lymphoma
  • Transformed Lymphoma
  • Triple-Hit Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of CC-97540, CD19-targeted NEX-T Chimeric Antigen Receptor (CAR) T Cells, in Subjects With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma
  • Official Title: A Phase 1, Multicenter, Open-label Study of CC-97540, CD19-targeted NEX-T Chimeric Antigen Receptor (CAR) T Cells, in Subjects With Relapsed or Refractory B-cell Non-Hodgkin Lymphoma

Clinical Trial IDs

  • ORG STUDY ID: CC-97540-NHL-001
  • SECONDARY ID: U1111-1244-9049
  • NCT ID: NCT04231747

Conditions

  • Lymphoma Non-Hodgkin
  • Agressive Lymphoma
  • Diffuse-large B-cell Lymphoma (DLBCL)

Interventions

DrugSynonymsArms
CC-97540CC-97540 monotherapy

Purpose

This is a Phase 1, first-in-human, open-label, multicenter study of CC-97540, CD19-targeted NEX-T chimeric antigen receptor (CAR) T cells, in subjects with relapsed or refractory B-cell non-Hodgkin lymphoma. The study will consist of 2 parts: dose-escalation (Part A) and dose-expansion (Part B). The dose-escalation part (Part A) of the study is to evaluate the safety and tolerability of increasing dose levels of CC-97540 to establish a recommended Phase 2 dose (RP2D); and the dose-expansion part (Part B) of the study is to further evaluate the safety, pharmacokinetics/pharmacodynamics, and efficacy of CC-97540 at the RP2D.

Trial Arms

NameTypeDescriptionInterventions
CC-97540 monotherapyExperimentalSubjects will be assigned to receive CC-97540 followed by 3 consecutive doses of lymphodepleting chemotherapy (fludarabine IV (30 mg/m2/day) and cyclophosphamide IV (300 mg/m2/day).
  • CC-97540

Eligibility Criteria

        Inclusion Criteria:

        Subjects must satisfy the following criteria to be enrolled in the study:

          1. Age ≥ 18 years at the time of informed consent.

          2. Signed written informed consent obtained prior to any study procedure.

          3. Willing and able to adhere to the study visit schedule and other protocol
             requirements.

          4. Relapsed and/or refractory aggressive B-cell NHL as defined:

               1. Histologically confirmed DLBCL not otherwise specified, high-grade B-cell
                  lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology
                  (HGBCL), transformed DLBCL from follicular (tFL) or marginal zone lymphoma
                  (tMZL), primary mediastinal B-cell lymphoma (PMBCL), or FL grade 3b (FL3B) AND

               2. Have relapsed and/or refractory disease after at least 2 lines of systemic
                  therapy which must include at least one anthracycline and rituximab (or other
                  anti-CD20 monoclonal antibody).

                  Note: Lines of therapy will exclude those given for prior indolent lymphoma. It
                  is not required for subjects to have had anthracycline for their DLBCL if
                  received for indolent disease AND/OR

               3. Have relapsed and/or refractory DLBCL failed to ASCT treatment. Note: ASCT
                  failure is defined as either failure to achieve an objective response (PR or
                  better), or disease progression after ASCT.

          5. Positron emission tomography (PET)-positive disease as per the Lugano Classification.

          6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

          7. Adequate organ function as detailed in the protocol.

          8. Adequate vascular access for leukapheresis.

          9. Willing and able to undergo tumor biopsies (in subjects with accessible disease).

         10. Agree to not donate blood, organs, sperm or semen, and egg cells for usage in other
             individuals as detailed in the protocol.

         11. Female and male subjects agree to use effective contraception as detailed in the
             protocol.

        Exclusion Criteria:

        The presence of any of the following will exclude a subject from enrollment:

          1. Uncontrolled medical, psychological, familial, sociological, or geographical
             conditions that do not permit compliance with the protocol, as judged by the
             Investigator; or unwillingness or inability to follow the procedures required in the
             protocol.

          2. Any condition including the presence of laboratory abnormalities, which places the
             subject at unacceptable risk if he/she were to participate in the study.

          3. Any condition that confounds the ability to interpret data from the study.

          4. Central nervous system (CNS)-only involvement by malignancy (note: subjects with
             pathologically-confirmed secondary CNS involvement are allowed).)

          5. Prior CAR T- cell or genetically-modified T- cell therapy, or prior CD19- targeted
             therapy (including, but not limited to, anti-CD19 mAbs or bispecific antibodies).)

          6. Treatment with the following therapies or procedure within the specified period:

               1. Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or
                  equivalent) within 14 days before leukapheresis administration. Physiologic
                  replacement, topical, and inhaled steroids are permitted.

               2. Cytotoxic chemotherapeutic agents (eg, doxorubicin, vincristine, gemcitabine,
                  oxaliplatin, carboplatin, etoposide) that are not considered lymphotoxic and
                  intrathecal therapy (IT) (see below) within 7 days of leukapheresis. Oral
                  chemotherapeutic agents, including lenalidomide and ibrutinib, are allowed if at
                  least 5 half-lives have elapsed prior to leukapheresis.

               3. Lymphotoxic chemotherapeutic agents (eg, cyclophosphamide, ifosfamide,
                  bendamustine) within 4 weeks of leukapheresis.

               4. Any experimental therapy within 8 weeks (for biologics) or 5 half-lives (for
                  small molecules) before leukapheresis

               5. Immunosuppressive therapies within 4 weeks of leukapheresis (eg, calcineurin
                  inhibitors, methotrexate or other chemotherapeutics, mycophenolate, rapamycin,
                  immunosuppressive antibodies such as anti-TNF, anti-IL6, or anti-IL6R)

               6. Donor lymphocyte infusions within 6 weeks of leukapheresis

               7. Radiation within 6 weeks of leukapheresis. Subjects must have progressive disease
                  in irradiated lesions or have additional non-irradiated, PET-positive lesions to
                  be eligible. Radiation to a single lesion, if additional non-irradiated
                  PET-positive lesions are present, is allowed up to 14 days prior to
                  leukapheresis.

               8. Autologous stem-cell transplant (SCT) (ie, Day 0 receipt of hematopoietic stem
                  cells) within 3 months of leukapheresis

               9. Washout of prior therapy (eg, bridging therapy for disease control)

          7. Active autoimmune disease requiring immunosuppressive therapy.

          8. Allogenic SCT (ie, Day 0 receipt of hematopoietic stem cells) within 6 months of
             leukapheresis or presence of ongoing symptoms or treatment for chronic graft-versus
             host disease (GVHD).)

          9. Hypersensitivity to fludarabine and/or cyclophosphamide.

         10. Prior history of malignancies, other than studied NHL, unless the subject has been
             free of the disease for ≥ 2 years except for the following non-invasive malignancies:

               1. Basal or squamous cell carcinoma of the skin

               2. Carcinoma in situ of the cervix or the breast

               3. Incidental histologic finding of prostate cancer (T1a or T1b using the TNM
                  (tumor, nodes, metastasis) clinical staging system) or prostate cancer that is
                  curative

               4. Other completely resected stage 1 solid tumor with low risk for recurrence

         11. Active hepatitis B, hepatitis C, or any human immunodeficiency virus (HIV) infection
             at the time of screening.

         12. Uncontrolled or active systemic fungal, bacterial, viral or other infection despite
             appropriate anti-infection treatment at the time of leukapheresis or pre-treatment
             evaluation.

         13. History of any one of the following cardiovascular conditions within the 6 months
             prior to screening: Class III or IV heart failure as defined by the New York Heart
             Association, myocardial infarction, unstable angina, angioplasty or stenting, or other
             clinically significant cardiac disease.

         14. History or presence of clinically significant CNS pathology such as seizure disorder,
             aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, or cerebellar
             disease. Presence of clinically active psychosis.

         15. History of ≥ Grade 2 hemorrhage within 30 days of screening.

         16. Pregnant or nursing (lactating) women.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse Events (AEs)
Time Frame:From the time of informed consent and follow up to 2 years after infusion of CC-97540
Safety Issue:
Description:An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the subject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE.ject's health, including laboratory test values, regardless of etiology. Any worsening (ie, any clinically significant adverse change in the frequency or intensity of a preexisting condition) should be considered an AE. An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a subject during the course of a study. It may be a new intercurrent illness, a worsening concomitant illness, an injury, or any concomitant impairment of the sub

Secondary Outcome Measures

Measure:Complete Response Rate (CRR)
Time Frame:Up to 2 years after CC-97540 infusion
Safety Issue:
Description:The proportion of subjects with a best overall response of complete response (CR).
Measure:Overall response Rate (ORR)
Time Frame:Up to 2 years after CC-97540 infusion
Safety Issue:
Description:The proportion of subjects achieving CR or partial response (PR).
Measure:Duration of response (DOR)
Time Frame:Up to 2 years after CC-97540 infusion
Safety Issue:
Description:The time from first response to progressive disease (PD) or death.
Measure:Time to response (TTR)
Time Frame:Up to 2 years after CC-97540 infusion
Safety Issue:
Description:Time from CC-97540 infusion to the first documentation of response (CR or PR).
Measure:Time to complete response (TTCR)
Time Frame:Up to 2 years after CC-97540 infusion
Safety Issue:
Description:Time from CC-97540 infusion to the first documentation of CR
Measure:Progression free survival (PFS)
Time Frame:Up to 2 years after CC-97540 infusion
Safety Issue:
Description:Time from CC-97540 infusion to the first documentation of PD, or death from any cause, whichever occurs first
Measure:Overall survival (OS)
Time Frame:Up to 2 years after CC-97540 infusion
Safety Issue:
Description:Time from CC-97540 infusion to death
Measure:Pharmacokinetics - peak expansion (Cmax)
Time Frame:Up to 2 years after CC-97540 infusion
Safety Issue:
Description:Maximum blood concentration
Measure:Pharmacokinetics -time to peak expansion (tmax)
Time Frame:Up to 2 years after CC-97540 infusion
Safety Issue:
Description:Time to peak (maximum) blood concentration
Measure:Pharmacokinetics - elimination half-life (t1/2)
Time Frame:Up to 2 years after CC-97540 infusion
Safety Issue:
Description:Elimination half-life
Measure:Pharmacokinetics - Area under curve (AUC)
Time Frame:Up to 2 years after CC-97540 infusion
Safety Issue:
Description:Area under the curve

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Juno Therapeutics, a Subsidiary of Celgene

Trial Keywords

  • Lymphoma
  • B-cell non-Hodgkin lymphoma
  • Agressive Lymphoma
  • Diffuse-large B-cell Lymphoma
  • DLBCL
  • NHL
  • CC-97540
  • CD19
  • NEX-T chimeric antigen receptor (CAR) T cells
  • CAR-T
  • CART

Last Updated

January 23, 2020