Clinical Trials /

Antigen-specific T Cell Therapy for Patients With Relapsed Refractory Multiple Myeloma

NCT04505813

Description:

This Research study is being done to characterize the safety, tolerability, and preliminary antitumor activity of the NEXI-002 T cell product (a new experimental therapy), which contains populations of CD8+ T cells targeting multiple Myeloma associated antigen peptides in patients with relapsed refractory multiple myeloma (MM). The study will enroll patients with MM who have relapsed or are refractory to standard lines of treatment. The enrolled patients will undergo bridging therapy for the purposes of disease control while the NEXI-002 T cell product is being manufactured. Choice of bridging therapy administered will be per the Investigator's discretion, but is limited to acceptable agents as specified in the protocol. Bridging therapy will be administered prior to lymphodepleting (LD) therapy, with the last dose of the bridging therapy administered ≥ 14 days prior to initiation of LD therapy. Within 72 hours after completing LD therapy, patients will receive a single IV infusion of the NEXI-002 T cell product.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Antigen-specific T Cell Therapy for Patients With Relapsed Refractory Multiple Myeloma
  • Official Title: A Phase 1 / 2 Study to Evaluate the Safety and Tolerability of Adoptively Transferred Autologous T Cells in Patients With Relapsed Refractory Multiple Myeloma

Clinical Trial IDs

  • ORG STUDY ID: NEXI-002-01
  • NCT ID: NCT04505813

Conditions

  • Relapsed Refractory Multiple Myeloma

Interventions

DrugSynonymsArms
NEXI-002 T CellsDose Expansion Phase

Purpose

This Research study is being done to characterize the safety, tolerability, and preliminary antitumor activity of the NEXI-002 T cell product (a new experimental therapy), which contains populations of CD8+ T cells targeting multiple Myeloma associated antigen peptides in patients with relapsed refractory multiple myeloma (MM). The study will enroll patients with MM who have relapsed or are refractory to standard lines of treatment. The enrolled patients will undergo bridging therapy for the purposes of disease control while the NEXI-002 T cell product is being manufactured. Choice of bridging therapy administered will be per the Investigator's discretion, but is limited to acceptable agents as specified in the protocol. Bridging therapy will be administered prior to lymphodepleting (LD) therapy, with the last dose of the bridging therapy administered ≥ 14 days prior to initiation of LD therapy. Within 72 hours after completing LD therapy, patients will receive a single IV infusion of the NEXI-002 T cell product.

Detailed Description

      The NEXI-002 is an adoptive cellular therapy product which contains populations of
      antigen-specific CD8+ T cells. The antigen-specific CD8+ T cells in the NEXI-002 T cell
      product are derived from Peripheral Blood Mononuclear Cells (PBMC) obtained from the original
      stem cell donor. During the manufacturing process, these cells are primed and expanded ex
      vivo using nano-size artificial Antigen Presenting Cells (aAPC) loaded with five leukemia
      associated antigen peptides in combination with a proprietary T cell enrichment and expansion
      process.

      The NEXI-002 T cell product is restricted to patients that are HLA-A2.01 allele positive for
      this study.

      There are two parts to this study, a Safety Evaluation Phase and a Dose Expansion Phase. The
      Safety Evaluation Phase will determine the safety and tolerability of a single dose of
      NEXI-002 T cell product, and will consist of Dose Escalation at two dose levels - each with
      cohorts of three patients.

      When all three patients at Dose Level 1 have dosed and cleared the DLT period, three
      additional patients will be enrolled at Dose Level 2. When three patients have cleared the
      DLT period at the highest dose level, that dose will be advanced to the Dose Expansion Phase.
      The Dose Expansion Phase will enroll up to 16 additional patients to further define the
      safety and evaluate the initial anti-tumor efficacy of the NEXI- 002 T cell product at the
      dose established from the Safety Evaluation Phase.

      All patients will enter a Post-Treatment Follow-Up period after infusion of the NEXI- 002 T
      cell product. During this phase, all patients will be monitored for AEs and followed for
      anti-leukemia response until the end of study visit is complete (up to one year).

      Additional assessments for safety, disease status, and other secondary and exploratory
      endpoints will also be monitored during the follow-up period.

      All patients will be followed for overall survival (OS) from time of disease progression
      until the last visit of the last patient. During this time, patients will be followed via
      telephone or other electronic contact at 12 week intervals for monitoring of OS.
    

Trial Arms

NameTypeDescriptionInterventions
Safety Evaluation PhaseExperimentalTreatment with NEXI-002 T cells, derived from PBMCs of the patient
  • NEXI-002 T Cells
Dose Expansion PhaseExperimentalDose Expansion Phase to further define the safety, tolerability and initial anti-tumor efficacy of the NEXI- 002 T cell product at the dose established from the Safety Evaluation Phase.
  • NEXI-002 T Cells

Eligibility Criteria

        Inclusion Criteria:

          -  Ability to provide informed consent and documentation of informed consent prior to
             initiation of any study-related tests or procedures that are not part of
             standard-of-care for the patient's disease. Patients must also be willing and able to
             comply with study procedures, including the acquisition of specified research
             specimens

          -  Age ≥ 18 years old & life expectancy > 3 months.

          -  Expression of HLA-A*0201 as determined by high resolution sequence-based typing method

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with exception
             of ECOG > 1 if related to recent bone fracture

          -  Patients must have confirmed diagnosis of MM

          -  Have identified relapsed/refractory disease which includes:

               1. Previous therapy consisting of at least three (3) standard regimens, including a
                  proteasome inhibitor, IMiD or anti-CD38 targeting therapy. Note: Induction
                  therapy, ASCT & maintenance therapy if given sequentially without intervening
                  progressive disease (PD) are considered one 'regimen'

               2. Refractory MM may be defined as disease that is refractory to treatment while on
                  therapy or that shows progression within 60 days of the last therapy

          -  Have measurable disease as defined by:

               1. Serum M protein ≥ 0.5 g/dL

               2. Urine M protein ≥ 200 mg/24hr

               3. Serum free light chains (FLC) ≥ 10 mg/dL with abnormal FLC ratio Note: Patients
                  with IgA MM in whom SPEP is deemed unreliable, due to co-migration of normal
                  serum proteins with the paraprotein in the β region, may be considered eligible
                  as long as total serum IgA level is > normal range.

          -  Acceptable laboratory parameters as follows:

             a) AST/ALT≤ 2.5 × ULN b)Total bilirubin ≤ 1.5 × ULN, except patients with Gilbert's
             syndrome, who may enroll if the conjugated bilirubin is within normal limits c) Serum
             creatinine ≤ 2.5 mg/dL or estimated creatinine clearance (CL) ≥ 30 mL/min & not
             dialysis-dependent d) ALC > 300 cells/µL e) ANC of ≥ 750 (without GCSF for 7days) f)
             Hb ≥ 8 (no transfusion for 7 days), ESA should be permissible e) Platelets ≥ 50 K
             (without platelets transfusion for 7 days). (≥30K if BM plasmacytosis is ≥ 50%).

          -  Recovery to Grade 1 or baseline of non-hematologic toxicities from prior treatments,
             excluding alopecia & Grade 2 peripheral neuropathy

          -  Female patients of childbearing potential must test negative for pregnancy at
             enrollment and during the study. Sexually active women of child-bearing potential,
             unless surgically sterile, must be willing to use a highly effective method of birth
             control defined as those which result in a low failure rate (i.e., less than 1% per
             year) such as implants, injectables, combined oral contraceptives, intra-uterine
             devices (IUDs) or vasectomized partner

          -  Male patients with partners of childbearing potential must be either vasectomized or
             agree to use a condom in addition to having their partners use another method of
             contraception resulting in a highly effective method of birth control defined as those
             which result in a low failure rate (i.e., less than 1% per year) such as implants,
             injectables, combined oral contraceptives, or IUDs. Patients should not have sexual
             intercourse with females who are either pregnant or lactating without double-barrier
             contraception

          -  Is not pregnant or breastfeeding, or expecting to conceive or father children within
             the projected duration of the trial, starting with the prescreening or screening visit
             through one year from administration of NEXI-002 T cells

        Exclusion Criteria:

          -  Have active cerebral or meningeal disease related to the underlying malignancy

          -  Have hemolytic anemia, plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS
             syndrome, amyloidosis, plasmacytoma, significant autoimmune or other malignant disease

          -  History of allogeneic hematopoietic stem cell transplantation

          -  Have active or uncontrolled infections with positive cultures and/or requiring
             treatment with IV anti-infective agents

          -  Echocardiogram or MUGA with left ventricular ejection fraction < 45%

          -  History of clinically significant cardiovascular disease including but not limited to:

               1. Myocardial infarction or unstable angina within the 6 months prior to the
                  initiation of study

               2. Stroke or transient ischemic attack within 6 months prior to initiation of study

               3. Clinically significant cardiac arrhythmia

               4. Uncontrolled hypertension: systolic blood pressure (SBP) > 180 mmHg, diastolic
                  blood pressure (DBP) > 100 mmHg

               5. Congestive heart failure (New York Heart Association [NYHA] class III-IV)

               6. Pericarditis or clinically significant pericardial effusion

               7. Myocarditis

          -  Clinically significant pulmonary compromise, including a requirement for supplemental
             oxygen use to maintain adequate oxygenation

          -  Eligible patients will not be on any steroids ≥10 mg per day prednisone or equivalent
             or other immunosuppressants such as tacrolimus, cyclosporine, etc.

             a)Intermittent topical, inhaled or intranasal corticosteroids are allowed

          -  History of symptomatic deep vein thrombosis (DVT) or pulmonary embolism (PE) requiring
             systemic anticoagulation within 6 months before enrollment

          -  History of autoimmune disease (e.g., Crohn's, rheumatoid arthritis, systemic lupus
             erythematosus, etc.) resulting in end organ injury or requiring systemic
             immunosuppression / systemic disease modifying agents within the last 2 year prior to
             enrollment. Subjects with a history of autoimmune-related hypothyroidism on a stable
             dose of thyroid replacement hormone and subjects with controlled Type 1 diabetes
             mellitus on a stable insulin regimen may be eligible for the study

          -  Human immunodeficiency virus (HIV) seropositive; HIV testing within 2 years of
             enrollment

          -  Seropositive for and with evidence of active viral infection with hepatitis B virus
             (HBV). Patients who are hepatitis B surface antigen (HBsAg) negative and HBV viral DNA
             negative are eligible

               1. Patients who had HBV but have received an antiviral treatment and show
                  non-detectable viral DNA for 6 months are eligible

               2. Patients who are seropositive because of HBV vaccine are eligible

          -  Seropositive for and with active viral infection with hepatitis C virus (HCV)

             a)Patients who had HCV but have received an antiviral treatment and show no detectable
             HCV viral DNA for 6 months are eligible

          -  Second primary invasive malignancy that has not been in remission for greater than 2
             years. Exceptions that do not require a 2-year remission include: related non-melanoma
             skin cancer; carcinoma in situ (cervix, bladder, breast, etc.) or squamous
             intraepithelial lesion on Pap smear; localized prostate cancer (Gleason score < 6); or
             resected melanoma in situ

          -  History of trauma or major surgery within 4 weeks prior to the study enrollment

          -  Any serious underlying medical or psychiatric condition that would impair the ability
             of the patient to receive or tolerate the planned treatment and follow up

          -  Known hypersensitivity to any component of NEXI-002 T cells, cyclophosphamide,
             fludarabine or tocilizumab

          -  Vaccination with any live virus vaccine is not permitted prior to the initiation of
             study treatment. Inactivated annual influenza vaccination is allowed

          -  Dementia or altered mental status that would preclude understanding and rendering of
             informed consent

          -  History of seizures, aphasia, psychosis or other chronic clinically significant
             neurologic disorders

             a)Patients with remote history of seizures that are well controlled on anti-seizure
             medications and without any seizure episode for 6 months are eligible

          -  Any issue that in the opinion of the investigator, would contraindicate the patient's
             participation in the study or confound the results of the study
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Adverse Events of Special Interest (AESIs) events
Time Frame:1 year
Safety Issue:
Description:1) Dose Limiting Toxicities (DLTs).

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:NexImmune Inc.

Last Updated

August 6, 2020