Clinical Trials /

QUILT 3.061: CD19 t-haNK in Subjects With Diffuse Large B-Cell Lymphoma

NCT04052061

Description:

Phase 1 study to assess the safety, preliminary efficacy of CD19 t-haNK and to determine the maximal tolerated dose and designate the recommended phase 2 dose in subjects with diffuse large B-cell lymphoma (DLBCL).

Related Conditions:
  • Diffuse Large B-Cell Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: QUILT 3.061: CD19 t-haNK in Subjects With Diffuse Large B-Cell Lymphoma
  • Official Title: Open-Label, Phase 1 Study of CD19 t-haNK In Subjects With Diffuse Large B-Cell Lymphoma Who Have Received 2 Or More Lines of Therapy And Are Ineligible For Transplant

Clinical Trial IDs

  • ORG STUDY ID: QUILT 3.061
  • NCT ID: NCT04052061

Conditions

  • Diffuse Large B Cell Lymphoma
  • Large-cell Lymphoma
  • Lymphoma, B-Cell
  • Lymphoma

Interventions

DrugSynonymsArms
CD19 t-haNKCD19 t-haNK

Purpose

Phase 1 study to assess the safety, preliminary efficacy of CD19 t-haNK and to determine the maximal tolerated dose and designate the recommended phase 2 dose in subjects with diffuse large B-cell lymphoma (DLBCL).

Detailed Description

      Phase 1 study to assess the safety, preliminary efficacy of CD19 t-haNK and to determine the
      maximal tolerated dose and designate the recommended phase 2 dose in subjects with diffuse
      large B-cell lymphoma (DLBCL). The study will be conducted in 2 parts: part 1 will involve
      dose escalation and part 2 will involve expansion of the recommended phase 2 dose.
    

Trial Arms

NameTypeDescriptionInterventions
CD19 t-haNKExperimentalCD19 t-haNK will be administered to patients with Diffuse Large B-Cell Lymphoma who have received 2 or more lines of therapy and are ineligible for transplant.
  • CD19 t-haNK

Eligibility Criteria

        Inclusion Criteria:

          1. Age ≥ 18 years old.

          2. Able to understand and provide a signed informed consent that fulfills the relevant
             Institutional Review Board (IRB) or Independent Ethics Committee (IEC) guidelines.

          3. Have histologically confirmed DLBCL that is refractory or relapsed after at least 2
             lines of previous therapy.

          4. Are ineligible for autologous stem cell transplant, allogeneic stem cell transplant or
             CAR T cell therapy under 1 of the following conditions:

               1. Have chemotherapy refractory disease after 2 lines of salvage chemotherapy.

               2. Have met eligibility for CAR T-cell therapy or transplant, but have refused
                  therapy.

          5. Have disease progression or relapse within 12 months after autologous or allogeneic
             stem cell transplant or have relapsed following CAR T-cell therapy and meet the
             following criteria:

               1. Had a partial response (PR) or stable disease (SD) at the 3-month disease
                  assessment and then subsequently progressed > 3 months after first CAR T-cell
                  therapy.

               2. Have confirmed CD19 tumor expression by biopsy after disease progression and
                  prior to retreatment.

               3. Have not received subsequent therapy for the treatment of lymphoma post CAR
                  T-cell therapy.

               4. Toxicities related to conditioning chemotherapy (fludarabine and
                  cyclophosphamide), with the exception of alopecia, have resolved to ≤ grade 1 or
                  returned to baseline prior to retreatment.

          6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.

          7. Have at least 1 measurable lesion and/or non-measurable disease evaluable in
             accordance with RECIST Version 1.1.

          8. Must have a recent formalin-fixed, paraffin-embedded (FFPE) tumor biopsy specimen
             obtained following the conclusion of the most recent anticancer treatment and be
             willing to release the specimen for exploratory tumor molecular profiling. If an
             historic specimen is not available, the subject must be willing to undergo a biopsy
             during the screening period, if considered safe by the Investigator. If safety
             concerns preclude collection of a biopsy during the screening period, a tumor biopsy
             specimen collected prior to the conclusion of the most recent anticancer treatment may
             be used.

          9. Must be willing to provide pre- and post-infusion blood samples for exploratory
             analyses.

         10. Ability to attend required study visits and return for adequate follow-up, as required
             by this protocol.

         11. Agreement to practice effective contraception for female subjects of child-bearing
             potential and non-sterile males. Female subjects of child-bearing potential must agree
             to use effective contraception while on study and for at least 5 months after the last
             dose of CD19 t-haNK for Infusion. Non-sterile male subjects must agree to use a condom
             while on study and for up to 5 months after the last dose of CD19 t-haNK for Infusion.
             Effective contraception includes surgical sterilization (eg, vasectomy, tubal
             ligation), two forms of barrier methods (eg, condom, diaphragm) used with spermicide,
             intrauterine devices (IUDs), and abstinence.

        Exclusion Criteria:

          1. Body weight at screening of ≤ 50 kg.

          2. Serious uncontrolled concomitant disease that would contraindicate the use of the
             investigational drug used in this study or that would put the subject at high risk for
             treatment-related complications.

          3. Systemic autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, Addison's
             disease, autoimmune disease associated with lymphoma).

          4. History of organ transplant requiring immunosuppression.

          5. History of or active inflammatory bowel disease (eg, Crohn's disease, ulcerative
             colitis).

          6. Inadequate organ function, evidenced by the following laboratory results:

               1. Absolute neutrophil count (ANC) < 750 cells/mm3.

               2. Platelet count < 75,000 cells/mm3.

               3. Hemoglobin < 9 g/dL.

               4. Total bilirubin greater than the upper limit of normal (ULN; unless the subject
                  has documented Gilbert's syndrome).

               5. Aspartate aminotransferase (AST [SGOT]) or alanine aminotransferase (ALT [SGPT])
                  > 2.5 × ULN (> 5 × ULN in subjects with liver metastases).

               6. Alkaline phosphatase (ALP) levels > 2.5 × ULN (> 5 × ULN in subjects with liver
                  metastases, or >10 × ULN in subjects with bone metastases).

               7. Serum creatinine > 2.0 mg/dL or 177

             Each study site should use its institutional ULN to determine eligibility.

          7. Uncontrolled hypertension (systolic > 160 mm Hg and/or diastolic > 110 mm Hg) or
             clinically significant (ie, active) cardiovascular disease, cerebrovascular
             accident/stroke, or myocardial infarction within 6 months prior to first study
             medication; unstable angina; congestive heart failure of New York Heart Association
             grade 2 or higher; or serious cardiac arrhythmia requiring medication.

          8. Dyspnea at rest due to complications of advanced malignancy or other disease requiring
             continuous oxygen therapy.

          9. Positive results of screening test for human immunodeficiency virus (HIV).

         10. Current chronic daily treatment (continuous for > 3 months) with systemic
             corticosteroids (dose equivalent to or greater than 10 mg/day methylprednisolone),
             excluding inhaled steroids. Short-term steroid use to prevent IV contrast allergic
             reaction or anaphylaxis in subjects who have known contrast allergies is allowed.

         11. Known hypersensitivity to any component of the study medication(s).

         12. Participation in an investigational drug study or history of receiving any
             investigational treatment within 14 days prior to dosing for this study, except for
             testosterone-lowering therapy in men with prostate cancer.

         13. Assessed by the Investigator to be unable or unwilling to comply with the requirements
             of the protocol.

         14. Concurrent participation in any interventional clinical trial.

         15. Pregnant and nursing women. A negative serum pregnancy test during screening and a
             negative pregnancy test within 72 hours prior to the first dose must be documented
             before CD19 t haNK for Infusion is administered to a female subject of child-bearing
             potential.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:MTD or HTD and RP2D.
Time Frame:1 year
Safety Issue:
Description:Maximum tolerated dose or highest tested dose and recommended phase 2 dose.

Secondary Outcome Measures

Measure:Objective Response Rate (ORR)
Time Frame:1 year
Safety Issue:
Description:ORR in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 and modified RECIST guidelines for immunotherapy trials (iRECIST).
Measure:Progression-free Survival (PFS)
Time Frame:1 year
Safety Issue:
Description:Progression-free Survival (PFS) by RECIST Version 1.1 and iRECIST.
Measure:Overall Survival (OS)
Time Frame:1 year
Safety Issue:
Description:OS will be evaluated using Kaplan-Meier methods.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:NantKwest, Inc.

Last Updated

August 8, 2019