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MT-3724_NHL_003: PK, PD, safety and tolerability of multiple-dose regimens of MT-3724 with lenalidomide for the treatment of patients with relapsed/refractory diffuse large B cell non-Hodgkin lymphoma

Description

The purpose of this study is to evaluate the safety and tolerability of MT-3724 in combination with lenalidomide in subjects with relapsed or refractory B-Cell NHL..

Status

Accepting new patients

Primary Study Objective(s)

The primary objectives for this clinical trial are:

  1. Tolerability as measured by number of subjects with dose limiting toxicities
  2. Safety measured by number of subjects with adverse events using

Core eligibility

Note: This is only a partial list of eligibility criteria.

Accepting patients who meet ALL these criteria:

  • Be adequately informed about the study and fully consent to participation as demonstrated by signing the written informed consent form before any screening procedure.
  • Men or women, aged 18 years or older who have relapsed or refractory B-cell NHL that, in the investigator's opinion, could benefit from MT-3724+LEN therapy.
  • At least one histology documented relapse of NHL by:
  • All subtypes of B-cell NHL may be considered for Part 1 (MT-3724 dose escalation). Only histologically documented DLBCL (including mixed histology) may be considered for Part 2 (expansion cohort).
  • Have received all available approved therapies for NHL. Those subjects who are ineligible for approved therapies in the opinion of the investigator, or have refused such therapies, will be eligible.
  • Have measurable disease by Lugano Classification for NHL (see Appendix 4):
  • Eastern Cooperative Oncology Group (ECOG) performance score of ≤2
  • Have adequate bone marrow function, as determined by all the following:
  • Have adequate kidney function, assessed by the estimated glomerular filtration rate (eGFR) ≥60 mL/min calculated by the CPK-EPI equation.
  • Have adequate hepatic function, as determined by:
  • Have adequate coagulation, as determined by:
  • Have adequate serum albumin, as determined by:
    • Albumin ≥ 3.0 g/dL
  • Women of reproductive potential must have a negative pregnancy test on 2 occasions during the screening period (within 10-14 days and within 24 hours before the start of treatment). Women not of reproductive potential are female subjects who are postmenopausal or permanently sterilized (e.g., hysterectomy, bilateral salpingectomy).
  • Males must agree to always use a latex or synthetic condom during any sexual contact with females of reproductive potential while taking LEN and for up to 4 weeks after discontinuing LEN, even if they have undergone a successful vasectomy. Male patients taking LEN must not donate sperm.
  • Subjects of reproductive potential and their partners must agree to either to abstain continuously from heterosexual intercourse or to use 2 methods of reliable birth control simultaneously to begin 4 weeks prior to initiating treatment with LEN until 28 days after the last dose of MT-3724 or LEN. The investigator or a designated associate should advise the subject how to achieve adequate contraception. The following birth control methods may be considered: one highly effective form of contraception - tubal ligation, IUD, hormonal (birth control pills, injections, hormonal patches, vaginal rings, or implants), or partner's vasectomy, and one additional effective contraceptive method - male latex or synthetic condom, diaphragm, or cervical cap.

Excluding patients who meet any of these criteria:

Medical and surgical history

  • History or current evidence of neoplastic disease that is histologically distinct from NHL, except cervical carcinoma in situ, superficial noninvasive bladder tumors, curatively treated Stage I-II non-melanoma skin cancer or any previous cancer curatively treated >2 years before the start of treatment.
  • Current evidence of new or growing brain or spinal metastases during screening. Subjects with known brain or spinal metastases may be eligible if they:
    • Had radiotherapy or another appropriate therapy for the brain or spinal metastases
    • Have no neurological symptoms (excluding Grade ≤2 neuropathy)
    • Have stable brain or spinal disease on the CT or MRI scan within 1 month of enrollment
    • Do not require chronic steroid therapy
  • History of allogeneic hematopoietic stem cell transplant within 180 days before the start of treatment.
  • Current evidence of acute or chronic Graft versus Host Disease.
  • Current evidence of CTCAE Grade >1 toxicity (except for hair loss, and those toxicities listed in other eligibility criteria) before the start of treatment.
  • Current evidence of incomplete recovery from surgery before the start of treatment, or planned surgery at any time during the study until the EoT Visit, except minor elective interventions deemed acceptable by the investigator.
  • History or current evidence of significant (CTCAE Grade ≥2) infection or wound within 4 weeks before the start of treatment.
  • History or current evidence of significant cardiovascular disease including, but not limited to the following conditions:
    • Unstable angina (symptoms of angina at rest) or new-onset angina within ≤3 months before the start of treatment.
    • Arterial thrombosis or pulmonary embolism within ≤3 months before the start of treatment.
    • Myocardial infarction or stroke within ≤3 months before the start of treatment.
    • Pericarditis (any CTCAE grade), pericardial effusion (CTCAE Grade ≥2), non malignant pleural effusion (CTCAE Grade ≥2) or malignant pleural effusion (CTCAE Grade ≥3).
    • Congestive heart failure (NYHA Class III or IV) at screening or LVEF <45%, assessed by Echo or MUGA scan within 1 month before starting study treatment. (Echo or MUGA scan performed within 6 months before screening and at least 28 days after the last cancer therapy is acceptable provided the subject has not received any potential cardiotoxic agents).
    • Cardiac arrhythmia requiring anti-arrhythmic therapy at screening. Subjects receiving digoxin, calcium channel blockers, or beta-adrenergic blockers are eligible at the investigator's discretion after consultation with Medical Monitor if the dose has been stable for ≥2 weeks before the start of treatment. Subjects with sinus arrhythmia and infrequent premature ventricular contractions are eligible at the investigator's discretion.
  • QTcF (Fridericia) >480 ms, determined as the average from three QTcF values on the triplicate ECG obtained at screening.
  • Current evidence of seropositive status for HIV, hepatitis B (positive for HBsAg or anti-HBsAg and anti-HBcAg antibodies) or hepatitis C (positive for anti-HCV antibody or HCV-RCV-RNA quantitation) as assessed by the applicable serology testing at screening.
    • Serology testing is not required if seronegativity is documented in the medical history and there are no clinical signs suggestive of HIV or hepatitis infection.
    • Subjects with positive HBV serology are eligible if quantitative PCR for plasma HBV-DNA is negative and the subject will be receiving prophylaxis for potential HBV reactivation.
    • Subjects with positive HCV serology are eligible if quantitative PCR for plasma HCV RNA is negative.
  • Women who are pregnant or breastfeeding.
  • History or current evidence of hypersensitivity to any of the study drugs, or of current hypersensitivity requiring systemic steroids at doses >20 mg/day prednisone equivalent.
  • History or current evidence of any other medical or psychiatric condition or addictive disorder, or laboratory abnormality that, in the opinion of the investigator, may increase the risks associated with study participation, or require treatments that may interfere with the conduct of the study or the interpretation of study results.

Prior treatments

  • Received anti-CD20 monoclonal antibody (Mab) therapy within the following periods before the start of treatment
    • Rituximab (Rituxan®): 84 days; if a subject had received rituximab within 37 Weeks before the start of treatment, then a serum rituximab level must be negative (<500 ng/mL) at screening.
    • Obinutuzumab (Gazyva®): 184 days
    • Ofatumumab (Arzerra®): 88 days
  • Received therapy for NHL (except the anti-CD20 Mab therapies listed above) within 4 weeks before the start of treatment.
  • Any investigational drug treatment from 4 weeks or 5 half-lives of the agent before the start of treatment, whichever is longer, until the EoT Visit.
  • Received radiotherapy to tumor lesions that would be chosen as target lesions (measurable disease) within 4 weeks before the start of treatment, unless the lesion exhibited objective progression between the radiotherapy and the screening according to the Lugano Classification for NHL.
    • Palliative radiotherapy to non-target lesions is allowed at the investigator's discretion.
  • Received any vaccines within 28 days of the start of treatment, or likely to require vaccines at any time from the start of treatment until 28 days after the last dose of MT-3724. Injectable flu vaccine (inactivated or recombinant) is permitted at the investigator's discretion.
  • Received systemic immune modulators within 2 weeks before the start of treatment
    • Systemic immune modulators include but are not limited to systemic corticosteroids at doses >20 mg/day of prednisone equivalent, cyclosporine and tacrolimus.
    • The use of non-steroidal anti-inflammatory drugs (NSAIDs) is permitted.
     

Accepting new patients

 

Learn more at

clinicaltrials.gov