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Non-hodgkin LymphomaPhase 2NCT03645395

Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of Multiple Dose Regimens of MT-3724 With Lenalidomide for the Treatment of Participants With Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma (MT-3724_NHL_003)

A Phase 2 study testing MT-3724 in people with Non-hodgkin Lymphoma, run by Molecular Templates, Inc. at 5 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to evaluate the safety and tolerability of MT-3724 in combination with Lenalidomide in participants with relapsed or refractory B-Cell NHL. Read more about this study

Who is it for?
Ages 18 to 101 years
Conditions the study is for
Non-hodgkin Lymphoma
What is being tested?
MT-3724
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
5 sitesUnited States
Study dates
8 Apr 2019to 10 Mar 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 101 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants must meet ALL the following criteria to be eligible for the study.
  • Be adequately informed about the study and fully consent to participation as demonstrated by signing the written ICF before any screening procedure.
  • Be aged ≥18 years years on the date of signing the informed consent form.
  • Have relapsed or refractory CD20 positive B-cell NHL that, in the investigator's opinion, could benefit from MT-3724+LEN therapy. Participants must have proof of CD20 positive NHL either by:
  • Historical biopsies (obtained with diagnosis of relapsed or refractory disease), or
  • Fresh biopsies.
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  • Bone marrow biopsy
  • Excisional lymph node biopsy
  • Core biopsy of any involved organ; all are acceptable methods; FNA not acceptable
  • 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 (MTD expansion cohort).
  • Have received all available approved therapies for NHL, one of which should be anti-CD20 based therapy.
  • Participants whose prior therapy includes chimeric antigen receptor t-cell (CAR-T) cell therapy are eligible.
  • Participants who underwent stem cell transplant (SCT) >100 days for autologous SCT or >180 days for allogeneic SCT before study drug administration and exhibited a full hematological recovery (consistent with the existing inclusion criteria requirements and without PRBC or platelet transfusions within 2 weeks of C1D1) prior to relapse are eligible.
  • Have bi-dimensionally measurable disease by Lugano Classification for NHL:
  • >1.5 cm LDi for lymph nodes
  • >1.0 cm LDi for extra nodal disease.
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤2
  • Have adequate bone marrow function, as determined by all the following:
  • Absolute neutrophil count (ANC) ≥1,000/mm³
  • Platelet count ≥50,000 mm³
  • Hemoglobin ≥8g/dL
  • Have adequate kidney function, creatinine clearance (CLcr) to be ≥50mL/min either measured or assessed by using the Cockcroft-Gault formula.
  • At the investigator's discretion, the eGFR result ≤50 mL/min may be verified by measurement of CLcr based on the 24-hour urine collection. Participants with CLcr ≥50 mL/min will be eligible irrespective of the eGFR result.
  • Have adequate hepatic function, as determined by:
  • Total bilirubin ≤1.5 x upper limit normal (ULN), or direct bilirubin ≤1.5 x ULN for participants with elevated total bilirubin secondary to Gilbert's Syndrome) and
  • Aspartate aminotransferase (AST) ≤3 x ULN (or ≤5 x ULN if liver involvement) and
  • Alanine aminotransferase (ALT) ≤3 x ULN (or ≤5 x ULN if liver involvement)
  • Have adequate coagulation, as determined by:
  • International Normalized Ration (INR) or Prothrombin Time (PT) ≤1.5 x ULN (unless on therapeutic anticoagulants)
  • Activated partial thromboplastin time (aPTT) ≤1.5 x ULN (unless on therapeutic anticoagulants)
  • 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 participants who are postmenopausal(>1 year since last menstrual cycle) 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 participants taking LEN must not donate sperm.
  • Participants 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 participants how to achieve adequate contraception. The following birth control methods may be considered: one highly effective form of contraception - tubal ligation, intrauterine device (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.
  • Participants must have a life expectancy of >3 months from the start of treatment.

Who cannot join

  • Participants who meet any of the following criteria must be excluded from the study.
  • 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. Participants with prior, curatively treated cancer >2 years ago before the start of treatment can be enrolled.
  • Current evidence of new or growing brain or spinal metastases during screening. Participants with known brain or spinal metastases may be eligible if they:
  • Had radiotherapy or another appropriate therapy for the brain or spinal metastases; concurrent prophylactic treatment is allowed.
  • Neurological symptoms must be stable and no worse than grade 2
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  • Have evidence of stable brain or spinal disease on computer topography (CT) or magnetic resonance imaging (MRI) scan obtained within 4 weeks of signing the ICF and compared with prior imaging results.
  • Do not require chronic steroid therapy, or if applicable, have been stable on steroid dose of no more than prednisone 20mg/day or equivalent by C1D1.
  • Current evidence of Graft versus Host Disease.
  • Current evidence of Common Terminology Criteria for Adverse Events (CTCAE) Grade >1 toxicity (before the start of treatment, except for hair loss, and those Grade 2 toxicities listed as permitted in other eligibility criteria).
  • Current evidence of incomplete recovery from surgery or radiotherapy before the start of treatment, or planned surgery or radiotherapy at any time during the study until the EoT Visit, except minor elective interventions deemed acceptable by the investigator.
  • Current evidence of significant (CTCAE Grade ≥2) infection or wound within 4 weeks before the start of treatment.
  • Participants with Grade 2 infection that has stabilized or improved with oral anti-infectives before the start of treatment may be eligible at the sponsor's discretion
  • 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 New York Heart Association (NYHA) Class III or IV at screening or left ventricular ejection fraction (LVEF) <45%, assessed by Echo or multiple-gated acquisition (MUGA) scan within 1 month before starting study treatment. (inclusion of participants with LVEF between 40%-45% should be discussed and approved by the sponsor). Echo or MUGA scan performed within 6 months before screening and at least 28 days after the last cancer therapy is acceptable provided the participant has not received any potential cardiotoxic agents since then.
  • Cardiac arrhythmia requiring anti-arrhythmic therapy at Screening. Participants 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 with MT-3724. Participants with sinus arrhythmia and infrequent premature ventricular contractions are eligible at the investigator's discretion.
  • QT interval corrected according to Fridericia's formula (QTcF) >480 ms, determined as the average from three QTcF values on the triplicate electrocardiogram (ECG) obtained at Screening.
  • Current evidence of uncontrolled HIV, HBV or HCV at screening. Serology testing is not required if seronegativity is documented in the medical history and if there are no clinical signs suggestive of HIV or hepatitis infections, or suspected exposure. The following exceptions apply for participants with positive viral serology:
  • Participants with HIV and an undetectable viral load and CD4+ T-cells counts ≥350 cells/microliter may be enrolled, but must be taking appropriate opportunistic infection prophylaxis, if clinically relevant.
  • Participants with positive HBV serology are eligible if they have an undetectable viral load and the participant will receive antiviral prophylaxis for potential HBV reactivation-per institutional guidelines.
  • Participants with positive HCV serology are eligible if quantitative PCR for plasma HCV RNA is below the lower limit of detection. Concurrent antiviral HCV treatment per institutional guidelines is allowed.
  • 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
  • Prior treatment with MT-3724.
  • Received anti-CD20 monoclonal antibody (Mab) therapy within the following periods before the start of treatment
  • Rituximab (Rituxan® RTX): 84 days; if a participant had received RTX within 37 Weeks before the start of treatment, then a serum RTX 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 and radioimmunoconjugates) 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 may be permitted at the investigator's discretion after consultation with the medical monitor.
  • Received any live vaccines within 4 weeks before of the start of treatment, unless the investigator believes the benefits outweigh the risks, after approval with the sponsor.
  • Require use of systemic immune modulators during study treatment. a. Systemic immune modulators include but are not limited to systemic corticosteroids at doses >20 mg/day or prednisone equivalent, cyclosporine and tacrolimus.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

United States5 sites
  • University of Maryland

    Baltimore, Maryland, 21201

  • Rush University

    Chicago, Illinois, 60612

  • University of Texas Southwestern

    Dallas, Texas, 75390

  • Boca Raton Clinical Research

    Plantation, Florida, 33322

  • Innovative Clinical Research Institute

    Whittier, California, 90603

Other trials in United States

About this study

Official title: A Phase 2a Open-label Study to Investigate Safety and Tolerability (Including the Maximum Tolerated Dose), Efficacy, Pharmacokinetics, Pharmacodynamics and Immunogenicity of MT-3724 in Combination With Lenalidomide in Subjects With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma

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

Read the detailed description

This is a multi-center, open-label two-part study evaluating the safety and tolerability of MT-3724 in combination with Lenalidomide in relapsed or refractory CD20 positive B-cell Lymphoma participants.

Part 1: (MT-3724 Dose Escalation) Define the maximum tolerated dose (MTD) of MT-3724 in combination with standard treatment of Lenalidomide

Part 2: (MTD Expansion Cohort) Confirm the safety and tolerability of the MTD of MT-3724 from Part 1 in the MTD Expansion Cohort, where MT-3724 will be given at the MTD in combination with Lenalidomide. In addition, the Pharmacokinetics (PK), Pharmacodynamics (PD), immunogenicity and tumor response at the MTD of MT-3724 in combination with Lenalidomide will be more thoroughly evaluated in Part 2.

It is anticipated that up to 64 participants will be enrolled. Treatment will continue until disease progression, withdrawal of consent or any other reason.

Being tested
MT-3724
Medical subject headings
Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MT-3724Drug

    Experimental treatment with MT-3724 in combination with LEN therapy.

Study groups in NCT03645395
Study groupRoleWhat they receive
MT-3724 10 mcg/kg-LENExperimentalMT-3724 10 mcg/kg/dose IV for 6 doses over 12 days (M-W-F X 2 weeks on Days 1, 3, 5, 8, 10, and 12) of each 28 day cycle in combination with LEN. If the treatment with MT-3724 is continued beyond Cycle 2, then MT-3724 will be administered weekly (Days 1, 3, 5, 8, 10, and 12) of each 28-day cycle
Receives: Drug: MT-3724
MT-3724 25 mcg/kg-LEN 3x a weekExperimentalMT-3724 25 mcg/kg/dose IV for 6 doses over 12 days (M-W-F X 2 weeks on Days 1, 3, 5, 8, 10, and 12) of each 28 day cycle in combination with LEN. If the treatment with MT-3724 is continued beyond Cycle 2, then MT-3724 will be administered weekly Days 1, 3, 5, 8, 10, and 12) of each 28-day cycle
Receives: Drug: MT-3724
MT-3724 20 mcg/kg-LEN 3x a weekExperimentalMT-3724 20 mcg/kg/dose IV for 6 doses over 12 days (M-W-F X 2 weeks on Days 1, 3, 5, 8, 10, and 12) of each 28 day cycle in combination with LEN. If the treatment with MT-3724 is continued beyond Cycle 2 , then MT-3724 will be administered weekly (Days 1, 3, 5, 8, 10, and 12) of each 28-day cycle
Receives: Drug: MT-3724
MT-3724 25 mcg/kg-LEN 2x a weekExperimentalMT-3724 25 mcg/kg dose IV for 4 doses (days 1, 5, 8 and 12 during cycles 1 and 2) of each 28 day cycle in combination with LEN and weekly during cycles 3 and beyond (days 1, 8, 15 and 22).
Receives: Drug: MT-3724
MT-3724 50 mcg/kg-LENExperimentalMT-3724 50 mcg/kg dose IV for 4 doses (days 1, 5, 8 and 12 during cycles 1 and 2) of each 28 day cycle in combination with LEN and weekly during cycles 3 and beyond (days 1, 8, 15 and 22).
Receives: Drug: MT-3724

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Part 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs) and Dose-limiting Toxicity

    An adverse event is any untoward medical occurrence or clinical investigation in a participant administered a pharmaceutical product(s) and which does not necessarily have to have a causal relationship with this experimental treatment(s). SAE is any untoward medical occurrence, at any dose; is fatal or life-threatening, is life-threatening, results in permanently disabling; results in unplanned in-patient hospitalization or prolongation of existing hospitalization; results in a congenital abnormality or birth defect; important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when based upon appropriate medical judgment, they may jeopardize the participant or may require medical or surgical intervention. A DLT is any TEAE that occurred after the start of infusion in cycle 1 of Part 1 and the TEAE is at least possibly related to the study drug, as determined by the sponsor after consultation with the investigator(s).

    Measured: Up to 1 year

  2. Part 1 and 2: Number of Participants With Abnormal Laboratory Parameters

    Laboratory parameters included hematology, blood chemistry, and urinalysis. Any abnormal laboratory test results which were considered clinically significant by the investigator were recorded on the case report form. Number of participants with any clinically significant abnormalities in laboratory parameters have been presented.

    Measured: Up to 1 year

  3. Part 1 and 2: Number of Participants With Clinically Significant Physical Findings

    This analysis was planned but data was not captured in the database. Abnormal changes were captured as adverse events if they were clinically significant.

    Measured: Up to 1 year

Secondary outcomes (8)
  1. Part 1 and 2: Plasma Concentrations of MT-3724

    Blood samples were collected for Pharmacokinetic (PK) analysis of MT-3724. Data could not be calculated due to small sample size and inconsistent sampling as a result of early termination.

    Measured: Days 1,3 and 12 of treatment cycle (Each cycle is of 28 days); Up to 1 year

  2. Part 1 and 2: Change From Baseline in B-cell Count

    Blood samples were collected for analysis of B-cell count. Data could not be calculated due to small sample size and inconsistent sampling as a result of early termination.

    Measured: Up to 1 year

  3. Part 1 and 2: Number of Participants With Anti-drug Antibody Titer When Treated With MT-3724

    Blood samples were collected for analysis of ADA titer. Data was not collected due to early termination of the trial.

    Measured: Up to 1 year

  4. Part 1 and 2: Number of Participants With Neutralizing Antibody (NAb) Titers When Treated With MT-3724

    Blood samples were planed to be collected for analysis of neutralizing antibody (NAb) titers. Data was not collected due to early termination of the trial.

    Measured: Up to 1 year

  5. Part 1 and 2: Number of Participants With Objective Response Rate (ORR)

    ORR was defined as CR or Partial Response (PR). CR: a score 1 (no uptake above background), 2 (uptake <=mediastinum), or 3 (<mediastinum but <=liver) with or without a residual mass on PET 5-PS, for lymph nodes and extralymphatic sites with no new lesions and no evidence of FDG-avid disease in bone marrow. PR: a score 4 (uptake moderately greater than [>] liver) or 5 (uptake markedly >liver and/or new lesions) with reduced uptake compared with baseline and residual mass(es) of any size on PET 5-PS for lymph nodes and extralymphatic sites with no new lesions and reduced residual uptake in bone marrow compared with baseline. Higher score indicates worse outcomes.

    Measured: Up to 1 year

  6. Part 1 and 2: Duration of Response (DOR)

    DOR is defined as the time from the first documented complete or partial response to the actual date of disease progression or death before progression. Data was not collected due to early termination of the trial.

    Measured: Up to 1 year

  7. Part 1 and 2: Progression Free Survival (PFS)

    PFS is defined as the time from first dose date until the first occurrence of documented disease progression or death from any cause in the absence of progressive disease. Data was not collected due to early termination of the trial.

    Measured: Up to 1 year

  8. Part 1 and 2: Overall Survival (OS)

    OS is defined as the time from date of start of treatment to date of death due to any cause. Data was not collected due to early termination of the trial.

    Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Aug 2018
  2. Study start8 Apr 2019
  3. Primary completion10 Mar 2021
  4. Study completion10 Mar 2021

Why it stopped: Sponsor decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03645395
Sponsor's protocol ID
MT-3724_NHL_003
Status last verified
Jul 2022
First submitted
19 Jul 2018
Last updated
16 Aug 2022
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing MT-3724 in people with Non-hodgkin Lymphoma, run by Molecular Templates, Inc. at 5 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 35 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 16 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 Aug 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Part 1 and 2: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious AEs (SAEs) and Dose-limiting Toxicity (time frame: Up to 1 year). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Aug 2022.

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