Clinical trial NCT05658562: A Study of MT-2111 in Patients With Relapsed/Refractory DLBCL
Official title: A Phase I/II Open-Label Study of MT-2111 in Patients With Relapsed/Refractory DLBCL
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Diffuse Large B-Cell Lymphoma
Lead sponsor: Mitsubishi Tanabe Pharma Corporation
Sponsor class: INDUSTRY
First posted: 2022-12-20
Enrollment: 49
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: \[Phase I part\] To investigate the safety, tolerability, and pharmacokinetics of MT-2111 monotherapy in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). In addition, the dose to be used in the Phase II part will be confirmed.

\[Phase II part\] To evaluate the efficacy of MT-2111 monotherapy in patients with relapsed/refractory DLBCL. In addition, the safety and pharmacokinetics will be investigated.


Eligibility criteria: Inclusion Criteria:

* Patients who were diagnosed pathologically with DLBCL, NOS, DLBCL transformed from indolent B-cell lymphoma, or high-grade B-cell lymphoma with DLBCL morphology and with MYC and BCL2 and/or BCL6 rearrangements, based on the 2017 WHO classification.
* Patients with relapsed or refractory disease despite 2 or more prior systemic therapies.
* Japanese patients aged ≥ 18 years at the time of informed consent. For Japanese subjects, it should be confirmed that the parents who are related by blood to the subject must be Japanese.
* Patients who have a lesion that can be assessed for staging and evaluated for response according to the Lugano criteria (2014). A lesion that has received radiotherapy as the most recent treatment will be considered as a measurable lesion only when progression has been documented following completion of the radiotherapy.
* Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 at screening.

Exclusion Criteria:

* Patients with a pathological diagnosis of Burkitt's lymphoma.
* Patients with bulky disease with the longest dimension of ≥ 10 cm.
* Patients with a history or complication of post-transplant lymphoproliferative disorders.
* Patients with lymphoma with active central nervous system involvement at the time of screening, including leptomeningeal disease.
* Patients complicated with other active malignancies or patients with a history of other malignancies within 3 years before informed consent. However, the following are exceptional:

  * Non-melanoma skin cancer
  * Non-metastatic prostate cancer
  * Cervical carcinoma in situ
  * Ductal carcinoma in situ or lobular carcinoma in situ
* Patients with clinically significant third space fluid accumulation (e.g., ascites requiring drainage or pleural effusion requiring drainage or associated with shortness of breath).
* Patients who underwent autologous hematopoietic stem cell transplantation (AHSCT) within 30 days prior to the start of study drug administration (Cycle 1 Day 1).
* For the Phase I part, patients with prior allogeneic stem cell transplantation (Allo-HSCT) before the start of study drug administration (Cycle 1 Day 1). For the Phase II part, patients undergoing Allo-HSCT within 60 days prior to the start of study drug administration (Cycle 1 Day 1).
* Patients who had a positive HIV antigen-antibody test or HIV antibody test.
* Patients positive for HBs antigen, HBc antibody, or HBs antibody. However, patients who meet any of the following are eligible:

  * The patient's HBs antibody positivity is clearly due to vaccination.
  * Patients who are positive for HBs antibody and/or HBc antibody with HBV-DNA not detected and agree to undergo HBV-DNA tests once a month from the start of study drug administration to at least 12 months after the completion of study drug administration.
* Patients positive for HCV antibody. However, patients with negative HCV-RNA are eligible.
* Patients who received anticancer therapy during the following periods prior to the start of study drug administration (Cycle 1 Day 1).

  * Cytotoxic chemotherapy: within 14 days.
  * Antibody therapy: within 5 half-lives or 14 days, whichever is longer (including monoclonal antibody preparations, radioimmunoconjugates, or antibody-drug conjugates). Within 14 days for rituximab, anti-CD3/CD20 bispecific antibody.
  * Radiotherapy: within 14 days
  * CAR-T therapy: within 100 days
  * Other anticancer therapy: within 14 days
* Patients who received treatment with any other investigational product within 14 days prior to the start of study drug administration (Cycle 1 Day 1). However, for the Phase I part, patients who received any other investigational product within 14 days or 5 half-lives, whichever is longer, before the start of study drug administration (Cycle 1 Day 1).

Primary outcomes:
measure: Overall response rate (ORR) by independent central review
timeFrame: From the date of first dose of study treatment until all participants completed treatment period or discontinued treatment (Up to 12 months)
Secondary outcomes:
measure: Duration of response (DOR)
timeFrame: The time from the date of first observation of complete response (CR) or partial response (PR) until progressive disease (PD) or death in patients with CR or PR observed (Up to 48 months)
measure: Complete response rate (CRR)
timeFrame: From the date of first dose of study treatment until all participants completed treatment period or discontinued treatment (Up to 12 months)
measure: Overall survival (OS)
timeFrame: The time from the date of first dose until death regardless of the occurrence of intercurrent event (Up to 48 months)
measure: Progression-free survival (PFS)
timeFrame: The time from the date of first dose until PD or death (Up to 48 months)
measure: Relapse-free survival (RFS)
timeFrame: The time from the date of first observation of CR until PD or death in patients with CR observed (Up to 48 months)
measure: Adverse events and adverse drug reactions
timeFrame: From the start of premedication until 15 weeks after the last dose of the study drug or until the start of new anticancer therapy, whichever comes first.
measure: Eastern Cooperative Oncology Group (ECOG) Performance Status
timeFrame: Screening to end of treatment (up to 30 days after the last dose) or data cut off
measure: Body weight
timeFrame: Screening to end of treatment (up to 30 days after the last dose) or data cut off
measure: 12-lead electrocardiogram (heart rate)
timeFrame: Screening to end of treatment (up to 30 days after the last dose) or data cut off
measure: 12-lead electrocardiogram [RR, PR, QRS, QT (QTcF)]
timeFrame: Screening to end of treatment (up to 30 days after the last dose) or data cut off
measure: 12-lead electrocardiogram (presence or absence of abnormal findings)
timeFrame: Screening to end of treatment (up to 30 days after the last dose) or data cut off
measure: Serum drug concentration
timeFrame: Please refer to the description above
measure: Anti-drug antibodies (including neutralizing antibodies)
timeFrame: Please refer to the description above.
Other outcomes:
Locations:
city: Nagoya-shi
country: Japan
facility: Nagoya Medical Center
state: Aichi
city: Nagoya-shi
country: Japan
facility: Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
state: Aichi
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Fukuoka-shi
country: Japan
facility: Kyushu Cancer Center
state: Fukuoka
city: Iizuka-shi
country: Japan
facility: Aso Iizuka Hospital
state: Fukuoka
city: Fukushima-shi
country: Japan
facility: Fukushima Medical University Hospital
state: Fukushima
city: Gifu-shi
country: Japan
facility: Gifu Municipal Hospital
state: Gifu
city: Ota-shi
country: Japan
facility: Gunma Prefectural Cancer Center
state: Gunma
city: Sapporo-shi
country: Japan
facility: Hokkaido Cancer Center
state: Hokkaido
city: Himeji-shi
country: Japan
facility: Japanese Red Cross Society Himeji Hospital
state: Hyogo
city: Yokohama-shi
country: Japan
facility: Kanagawa Cancer Center
state: Kanagawa
city: Kyoto-shi
country: Japan
facility: University Hospital, Kyoto Prefectural University of Medicine
state: Kyoto
city: Sendai-shi
country: Japan
facility: Tohoku University Hospital
state: Miyagi
city: Matsumoto-shi
country: Japan
facility: Shinshu University Hospital
state: Nagano
city: Nagasaki-shi
country: Japan
facility: Japanese Red Cross Nagasaki Genbaku Hospital
state: Nagasaki
city: Osaka-shi
country: Japan
facility: Osaka Saiseikai Nakatsu Hospital
state: Osaka
city: Osaka-shi
country: Japan
facility: Medical Research Institute KITANO HOSPITAL, PIIF Tazuke-kofukai
state: Osaka
city: Izumo-shi
country: Japan
facility: Shimane University Hospital
state: Shimane
city: Bunkyo-ku
country: Japan
facility: Tokyo Metropolitan Komagome Hospital
state: Tokyo
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Koto-ku
country: Japan
facility: Cancer Institute Hospital of JFCR
state: Tokyo
city: Tachikawa-shi
country: Japan
facility: Disaster Medical Center
state: Tokyo
city: Yamagata-shi
country: Japan
facility: Yamagata University Hospital
state: Yamagata
Study officials:
affiliation: Mitsubishi Tanabe Pharma Corporation
name: General Manager
role: STUDY_DIRECTOR
References: