Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Letetresgene Autoleucel Engineered T Cells Alone and in Combination With Pembrolizumab in NY-ESO-1 Positive Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03168438
Recruitment Status : Terminated (The study was terminated following an internal review of the company's research and development portfolio)
First Posted : May 30, 2017
Last Update Posted : February 25, 2021
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
This trial will evaluate safety, tolerability, and efficacy of letetresgene autoleucel (GSK3377794) with or without pembrolizumab in participants with relapsed and refractory multiple myeloma.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: Letetresgene autoleucel Drug: Letetresgene autoleucel with pembrolizumab Drug: Fludarabine Drug: Cyclophosphamide Drug: Pembrolizumab Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Open-Label Pilot Study to Assess the Safety, Tolerability and Antitumor Activity of Genetically Engineered NY-ESO-1 Specific (c259) T Cells Alone or in Combination With Pembrolizumab in HLA-A2+ Subjects With NY-ESO-1 and/or LAGE-1a Positive Relapsed and Refractory Multiple Myeloma
Actual Study Start Date : August 18, 2017
Actual Primary Completion Date : July 13, 2020
Actual Study Completion Date : November 5, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Arm 1: Letetresgene autoleucel (GSK3377794)
Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive letetresgene autoleucel (GSK3377794), as a single intravenous (IV) infusion after completing lymphodepleting chemotherapy.
Drug: Letetresgene autoleucel
Letetresgene autoleucel (GSK3377794) as an IV infusion

Drug: Fludarabine
Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.

Drug: Cyclophosphamide
Cyclophosphamide will be used as lymphodepleting chemotherapy and will be administered via IV route.

Experimental: Arm 2: Letetresgene autoleucel (GSK3377794) with pembrolizumab
Eligible participants will be leukapheresed to manufacture engineered T-cells. Participants will then receive letetresgene autoleucel (GSK3377794), as a single intravenous (IV) infusion after completing lymphodepleting chemotherapy, followed by pembrolizumab 200 mg every 3 weeks.
Drug: Letetresgene autoleucel with pembrolizumab
Letetresgene autoleucel (GSK3377794) as an IV infusion, followed by pembrolizumab every 3 weeks

Drug: Fludarabine
Fludarabine will be used as lymphodepleting chemotherapy and will be administered via IV route.

Drug: Cyclophosphamide
Cyclophosphamide will be used as lymphodepleting chemotherapy and will be administered via IV route.

Drug: Pembrolizumab
Pembrolizumab is available as an IV infusion




Primary Outcome Measures :
  1. Number of participants with adverse events (AEs)and serious adverse events (SAEs) [ Time Frame: Up to 108 weeks ]
    AEs and SAEs will be collected

  2. Number of participants with abnormal laboratory paramaters [ Time Frame: Up to 108 weeks ]
    Blood samples will be collected for the assessment of hematology, clinical chemistry and coagulation parameters

  3. Number of participants with abnormal cardiac assessments by electrocardiogram (ECG) [ Time Frame: Up to 108 weeks ]
    The following cardiac parameters will be measured: Heart rate, heart rhythm, PR Interval, RR Interval, QRS Interval and QT interval corrected (QTc) (Fridericia's or Bazett's correction)


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: Up to 108 weeks ]
    Overall Response Rate is defined as the proportion of participants with a confirmed stringent complete response (sCR), complete response (CR), very good partial response (VGPR) and partial response (PR) using IMWG uniform response criteria for MM

  2. Time to Response (TTR) [ Time Frame: Up to 108 weeks ]
    Time to response is defined as the time from date of T-cell infusion to initial date of response of the participant who achieved confirmed sCR, CR, VGPR or PR

  3. Duration of Response (DOR) for all participants who achieve at least PR [ Time Frame: Up to 108 weeks ]
    Duration of response is defined as the time from the initial date of response of the participants who achieved confirmed sCR, CR, VGPR or PR to the date of progressive disease or death

  4. Progression-free survival (PFS) [ Time Frame: Up to 108 weeks ]
    Progression free survival is defined as the time from the date of T cell infusion until first documented sign of disease progression or death due to any cause.

  5. Maximum persistence (Cmax) [ Time Frame: Up to 108 weeks ]
    Serial blood samples will be collected at specific timepoints for evaluation of Cmax.

  6. Time to Cmax (Tmax) [ Time Frame: Up to 108 weeks ]
    Serial blood samples will be collected at specific timepoints for evaluation of Tmax.

  7. Area under the time curve from zero to time t (AUC 0-t) [ Time Frame: Up to 108 weeks ]
    Serial blood samples will be collected at specific timepoints for evaluation of AUC (0 to t).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age >=18 years of age or older on the date of signing informed consent.
  • Histologically confirmed diagnosis of secretory multiple myeloma with myeloma markers at levels defined in the protocol.
  • Documented diagnosis of relapsed and refractory multiple myeloma (RRMM) (at least 3 prior regimens and responsive to at least 1, and refractory to most recent prior therapies, which must have included one or more than one drug from each of the following drug classes: an immunomodulatory imide drug (IMiD), proteasome inhibitor, alkylator (unless the participant is ineligible or contraindicated to receive an alkylator), CD 38 monoclonal antibody, and glucocorticoid as separate lines or a combined line of therapy.- Left ventricular ejection fraction (LVEF) >= 50%. Lower LVEF (>= 40%) permissible if formal cardiologic evaluation reveals no evidence for clinically significant functional impairment.
  • Meets protocol criteria for patients who have previously received checkpoint inhibitors or other immuno-oncology agents.
  • ECOG Performance Status 0 or 1.
  • Participant is HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06 positive as determined by a designated central laboratory.
  • Participant has confirmed sufficient expression of NY-ESO-1 and/or LAGE-1a as determined by a designated central laboratory.
  • In the Investigator's opinion, the participant is fit for cell collection.
  • Participant has adequate organ function and cell counts as described in the protocol.
  • Participants previously treated with BCMA therapy (BCMA chimeric antigen receptor (CAR)-T, antibody-drug conjugate (ADC), or other type of BCMA-targeted therapy) must have progressed from this therapy prior to attending the Baseline visit prior to beginning lymphodepletion.
  • Contraception use by male and female participant meets protocol requirements.

Exclusion Criteria:

  • Has only plasmacytomas, plasma cell leukemia, monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), non-secretory myeloma or primarily amyloidosis.
  • Previously received anti- programmed death (PD)-1, anti-PD-ligand (L)1, or anti-PD-L2 inhibitor.
  • Previously participated in Merck pivotal trial NCT02576977: Study of Pomalidomide and Low Dose Dexamethasone With or Without Pembrolizumab in Refractory or RRMM.
  • Had a prior allogeneic stem cell transplant.
  • Has ongoing toxicity from previous anticancer therapy.
  • Had a major surgery within 4 weeks prior to enrollment.
  • Has history of allergic reactions to fludarabine, cyclophosphamide or agents similar to fludarabine, cyclophosphamide or other agents used in the study.
  • Known history of myelodysplasia.
  • Current active liver or biliary disease.
  • Known history of chronic active hepatitis or liver cirrhosis.
  • Participant has an active viral infection.
  • History of severe immune disease, including non-infectious pneumonitis, requiring steroids or other immunosuppressive treatments.
  • Active immune-mediated diseases.
  • Prior or active demyelinating disease.
  • Evidence or history of significant cardiac disease.
  • Evidence or history of other significant, hepatic, renal, ophthalmologic, psychiatric, or gastrointestinal disease.
  • Participants with concomitant second malignancies (except adequately treated non-melanomatous skin cancers, carcinoma in situ of the breast, treated superficial bladder cancer or prostate cancer, or in situ cervical cancers ) not in complete remission.
  • Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may be eligible.
  • Active bacterial or systemic viral or fungal infections.
  • Pregnant or breastfeeding.
  • Cannot meet washout periods for prior radiotherapy, chemotherapy or other protocol-specified therapies.
  • More than 2 years have passed since the participant's last leukapheresis collection.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03168438


Locations
Layout table for location information
United States, California
GSK Investigational Site
Duarte, California, United States, 91010
United States, Florida
GSK Investigational Site
Miami, Florida, United States, 33136
GSK Investigational Site
Tampa, Florida, United States, 33612-9497
United States, Georgia
GSK Investigational Site
Atlanta, Georgia, United States, 30322
United States, Maryland
GSK Investigational Site
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
GlaxoSmithKline
Merck Sharp & Dohme Corp.
Investigators
Layout table for investigator information
Study Director: GSK Clinical Trials GlaxoSmithKline
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03168438    
Other Study ID Numbers: 208470
ADP-0011-008 ( Other Identifier: Adaptimmune Therapeutics )
KEYNOTE-487 ( Other Identifier: Merck Sharp and Dohme Corp. )
First Posted: May 30, 2017    Key Record Dates
Last Update Posted: February 25, 2021
Last Verified: February 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Relapsed and Refractory Multiple Myeloma
T Cell Receptor
Immuno-oncology
NY-ESO-1
Leukapheresis
Adoptive TCR T-cell therapy
Letetresgene autoleucel
Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Pembrolizumab
Fludarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Immunological