Status and phase
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About
This study is a Phase 1 multicenter study with a Dose Escalation and Dose Expansion evaluating safety and efficacy of MT-601 administration to patients with Relapsed or Refractory Lymphoma. The starting dose administered is 200 x 10^6 cells (flat dosing).
Full description
This study is a Phase 1, multicenter, open-label study designed to evaluate the safety and efficacy of MT-601 in participants with relapsed or refractory (R/R) non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) who either relapsed or had incomplete response after cluster of differentiation (CD) 19-directed chimeric antigen receptor (CAR) T cell therapy or are CAR T cell therapy naïve (ineligible or refused CD19-directed CAR T cell therapy or for whom CAR T cell therapy is not available). The study will consist of two portions or phases: 1) Dose Escalation with allowance for backfilling cohorts (up to 50 participants) followed by 2) Dose Expansion at the preliminary RP2DS in 1-2 disease specific cohorts of up to 29 participants each. The Dose Expansion portion of this study will begin after completion of the Dose Escalation portion. The purpose of the Dose Expansion portion of the study is to evaluate the clinical efficacy of MT-601 at the dose determined to be safe in the Dose Escalation portion.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Participants are eligible to be included in the study only if all of the following criteria apply and the participant, in the judgement of the Investigator, is an appropriate candidate for experimental therapy:
General:
Participant must be ≥ 18 years of age and capable of giving signed informed consent (ICF), which includes compliance with the requirements and restrictions listed in the ICF and in the protocol, at the time of signing the ICF.
Disease Specific:
Cytologically or histologically confirmed diagnosis of NHL, HL or CLL based on the 2022 World Health Organization (WHO) criteria for hematolymphoid neoplasms
Enrollment of the following subtypes will be eligible:
LBCL including diffuse large B cell lymphoma, primary mediastinal B cell lymphoma (PMBCL), high grade B cell lymphoma (HGBL), T cell rich B cell lymphoma and transformed indolent lymphoma (transformed iNHL)
FL
MCL
MZL
HL
The following additional subtypes may be enrolled in disease specific cohorts during Dose Expansion (upon approval by Sponsor)
CLL/SLL
CNS lymphoma
CAR T cell refractory
Must have measurable disease as per 2014 Lugano criteria or 2018 iwCLL criteria. Participants with splenic MZL must have measurable splenomegaly on imaging or evidence of bone marrow involvement.
Prior Treatments
Participants who are R/R, are intolerant to, or are considered ineligible for systemic standard of care anticancer treatments, including at least 2 prior therapies. Participants who refuse standard of care treatments may also be considered if documentation is provided that he/she has been made aware of all therapeutic options.
For participants with LBCL, FL, and MCL: Have received CD19-directed CAR T cell therapy and relapsed ≥ 30 days or attained an incomplete response as the best response within 1 year after CAR T cell administration. Participants who refuse or are ineligible for CAR T cell therapy are eligible for this study. Note: during Dose Expansion, a specific cohort may be enrolled to evaluate participants who were refractory to CD19-directed CAR T cell therapy.
Health Status
Karnofsky score of ≥70 or performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale
Life expectancy ≥12 weeks
Adequate blood, liver, renal and cardiac function:
Female: Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective (i.e., with a failure rate of < 1% per year), preferably with low user dependency during the intervention period and for at least 6 months after the last infusion of MT-601 and agrees not to donate eggs (i.e., ova and oocytes) for the purpose of reproduction during this period
Male participants are eligible to participate if they agree to the following during the intervention period and for at least 6 months after the last infusion of MT-601:
Refrain from donating sperm
PLUS either:
Be abstinent from intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agree to remain abstinent OR Must agree to use a male condom AND should also be advised of the benefit for a nonpregnant female partner to use a highly effective method of contraception as a condom may break or leak
Exclusion criteria
Disease-related
Evidence of bulky disease at the time of the conditioning regimen (≥ 10 cm in diameter for LBCL or HL and > 6 cm for other subtypes)
Untreated or ongoing treatment for CNS lymphoma or completed treatment within 2 weeks of apheresis (Note: May be allowed in Dose Expansion if disease specific cohort for CNS lymphoma is opened)
Refractory to CAR T therapy defined as a best response of stable disease or disease progression (Note: May be allowed in Dose Expansion if disease specific cohort for CAR T cell therapy refractory is opened)
Requirement for urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression Medical Conditions
Primary immunodeficiency
Severe or uncontrolled autoimmune disorder
History or presence of clinically relevant CNS pathology such as epilepsy, seizure, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
Unresolved immune effector cell-associated neurotoxicity syndrome (ICANS) from prior CAR T cell administration. Consideration for Grade 1 may be made after discussion with the Medical Monitor
History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g., cervix, bladder, breast, and/or prostate) unless disease free for at least 3 years
Cardiac conditions:
Oxygen saturation at room air < 92%
Participant has known human immunodeficiency virus (HIV) infection, or active hepatitis B virus (HBV)/hepatitis C virus (HCV) infection
Acute bacterial, viral, fungal infection requiring systemic therapy (uncomplicated urinary tract infection and bacterial pharyngitis are permitted if responding to therapy)
History of severe allergic reactions to any of the study intervention components including conditioning regimen, dimethyl sulfoxide (DMSO) or to tocilizumab
Clinically significant reversible toxicities from prior cancer therapy that have not recovered to Grade 1 or baseline
Prior/Concomitant Therapy
Prior to Apheresis:
Receipt of allogeneic hematopoietic cell transplant (HCT) within 12 months; on immunosuppression or with evidence of donor/mixed chimera
Receipt of autologous HCT within 3 months
Treatment with CD19-directed CAR T cell therapy within 3 months
Treatment with bispecific antibody within 1 month
Treatment with antibody drug conjugates (ADC's) or PD-1/PD-L1 within 21 days
Treatment with monoclonal antibodies impacting T cell function within 14 days
Treatment with systemic immunosuppression including systemic corticosteroids (unless ≤5 mg/day oral prednisone or steroid equivalent) within 14 days
Treatment with chemotherapy within 7 days
Prior to the conditioning regimen:
Treatment with a live, attenuated vaccine within 4 weeks
Treatment with antibody drug conjugates (ADC's) or PD-1/PD-L1 within 21 days
Treatment with chemotherapy or biologics/monoclonal antibodies within 14 days
Treatment with radiation therapy within 7 days
Treatment with a tyrosine kinase inhibitor (TKI) within 7 days or 5 half-lives (whichever is longer) before conditioning regimen
Hematopoietic growth factors <2 days
At either time:
Treatment with experimental CAR T cell product unless approved by Medical Monitor
Treatment with other cancer therapy including investigational agents that do not fit in the above categories within 14 days
Major surgery within 14 days
Other
Pregnant or lactating
Any other issue which, in the opinion of the treating physician, would make the participant ineligible for the study
Primary purpose
Allocation
Interventional model
Masking
79 participants in 1 patient group
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Central trial contact
Monic Stuart, MD; Patricia Allison
Data sourced from clinicaltrials.gov
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