A Phase 1 / 2 Study to Evaluate the Safety and Tolerability of Adoptively Transferred Autologous T Cells in Patients With Relapsed Refractory Multiple Myeloma
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Relapsed Refractory Multiple Myeloma
- Sponsor
- NexImmune Inc.
- Enrollment
- 9
- Locations
- 6
- Primary Endpoint
- Progressive Free Survival
- Status
- Suspended
- Last Updated
- 2 years ago
Overview
Brief Summary
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 patient. 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.
Investigators
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:
- •Previous therapy consisting of at least three (3) standard regimens, including a proteasome inhibitor, IMiD, or anti-CD38 targeting therapy.
- •Note: Induction therapy, autologous stem cell transplantation (ASCT) \& maintenance therapy if given sequentially without intervening progressive disease (PD) are considered one 'regimen'
- •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:
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:
- •Myocardial infarction or unstable angina within the 6 months prior to the initiation of study
- •Stroke or transient ischemic attack within 6 months prior to initiation of study
- •Clinically significant cardiac arrhythmia
- •Uncontrolled hypertension: systolic blood pressure (SBP) \> 180 mmHg, diastolic blood pressure (DBP) \> 100 mmHg
Outcomes
Primary Outcomes
Progressive Free Survival
Time Frame: At 12 months
Median Progressive free Survival (PFS)
Overall Response Survival (Rate)
Time Frame: At 12 months
Overall Response Rate (ORR)
Adverse events (AEs) Reporting
Time Frame: At year 1
Incidence of TEAEs leading to study withdrawal
Adverse Events of Special Interest (AESIs) events
Time Frame: 1 year
1) Dose Limiting Toxicities (DLTs).
Survival
Time Frame: At 12 months
Overall Survival (OS)
Adverse Events of Special Interest (AESIs) events (AEs) Reporting
Time Frame: at year 1
Cytokine Release Syndrome (CRS)
Adverse Events of Special Interest (AESIs)events (AEs) Reporting-TEAEs
Time Frame: At year 1
For Incidence of TEAEs and serious TEAEs (Treatment-emergent adverse events (TEAEs) are defined as those AEs that started on or after LD therapy or that worsened after LD therapy.
Adverse Events of Special Interest (AESIs)events (AEs) Reporting (ICANS)
Time Frame: at year 1
Immune effector Cell-Associated Neurotoxicity Syndrome (ICANS)
Adverse Events of Special Interest (AESIs)events (AEs) Reporting-Infusion Reactions
Time Frame: At year 1
Infusion Related Reactions (IRR)