Extended Treatment Access Study of MT-3724 for Subjects with Relapsed non-Hodgkin’s B-Cell Lymphoma or B-Cell Chronic Lymphocytic Leukemia Who Have Completed Phase I/Ib Study MT-3724_NHL_001_US
Michelle A. Fanale
You are being asked to take part in this study because you have completed the MD Anderson clinical research study, 2014-0504, without any intolerable side effects. The non-Hodgkin’s B-cell lymphoma (NHL) or chronic lymphocytic leukemia (CLL) did not get worse while you were taking MT-3724.' The goal of this clinical research study is to provide continued access to MT-3724 to patients who were taking it as part of the 2014-0504 study. Researchers also want to learn about the safety of continuing to receive MT-3724.
Disease Group: Lymphoma
Treatment Agent: MT-3724
Treatment Location: Both at MDACC & and Other Sites
Sponsor: Molecular Templates, Inc.
1. Provide extended access to MT-3724 on a compassionate use basis for subjects who require treatment for their NHL or CLL and have (i) tolerated MT-3724 throughout the MT-3724_NHL_001_US Phase I/Ib study (Core and Repeat Dosing), (ii) maintained stable disease or better, and (iii) have no other acceptable and better treatment options available to them in the Investigator’s judgment. 2. Identify the frequency and nature of clinical and laboratory adverse events (AEs), both reported and observed,as a measure of safety and tolerability over repeated cycles of MT-3724 beyond those administered in the MT-3724_NHL_001_US Phase I/Ib study. Exploratory Objective: 1. Assessment of cancer response by physical exam, clinical symptoms, cancer response (e.g., imaging, blood counts), and Eastern Cooperative Oncology Group (ECOG) performance status. • Anti-MT-3724 antibodies (ADA) in serum at baseline and at Final Study Visit will be assessed. Additional serum samples for ADA may be obtained.
IRB Review and Approval Date: 01/20/2016
Recruitment Status: Open
Projected Accrual: 40
1) Eligible subjects must be adequately informed of all study procedures
and fully consent to participation as demonstrated by signing the
Informed Consent Form (ICF).
2) Eligible subjects must require treatment for their NHL and have: a. tolerated MT-3724 throughout the MT-3724_NHL_001_US Phase I/Ib study (Core and Repeat Dosing), b. successfully completed the Core and Repeat Dosing portions of MT-3724_NHL_001_US Phase I/Ib study as defined by that protocol, c. received no other treatment for their NHL since enrollment in the MT-3724_NHL_001_US Phase I/Ib study, d. maintained stable disease or better throughout that study and e. been assessed by the investigator to have no other acceptable and better treatment options available to them. The investigator must document in the potential subject’s medical record that there are no other approved treatment options available and/or appropriate for the potential subject or that the potential subject has declined any other approved treatment options that me be available to them.
3) Males or females 18 years or older
4) Potential subjects must have received all approved therapies known to provide clinical benefit for their disease subtype and for which they are eligible or must have refused these treatment options prior to consideration for continued compassionate use treatment with MT-3724 through enrollment in this protocol. In the case of subjects who have lymphomas for which high-dose chemotherapy and autologous stem cell transplantation (HD-ASCT) is considered a standard curative therapy, eligibility for MT-3724 compassionate use requires that the subject’s disease relapsed after HD-ASCT, that the subject is not eligible for HD ASCT, or that the subject has refused HD-ASCT.
5) Potential subjects with known central nervous system (CNS) metastases may be enrolled if they: 1. have previously been treated with radiotherapy for their CNS disease, 2. do not require chronic steroid therapy, 3. have had computed tomography or magnetic resonance imaging of the brain within 1 month of this study’s entry that showed stable disease and 4. have no neurological symptoms (excluding Grade 1 or 2 neuropathy).
6) Eastern Cooperative Oncology Group (ECOG) performance status of </= 3.
7) Potential subjects should have measurable disease (any tumor mass of at least 1.5 cm) which has been documented to not have progressed during the MT-3724_NHL_001_US Phase I/Ib study and which can be followed during extended treatment for possible new disease progression.
8) Potential subjects must be at least 9 days past their last course of MT-3724 treatment and have recovered from any side effects attributed to MT-3724 to at least Common Terminology Criteria for Adverse Events (CTCAE, v. 4.03) Grade 2 prior to initiating additional cycles of MT-3724 through this compassionate use protocol. Subjects with pre-existing AEs at screening that are severe or life threatening by CTCAE grading should not be enrolled.
9) Laboratory requirements: a) Absolute neutrophil count (ANC) > 1,000 per microliter (µL) b) Platelet count > 25,000/µL (The potential subject must be asymptomatic and the thrombocytopenia must be secondary to bone marrow infiltration by tumor and not secondary to increased platelet consumption or the effect of previous marrow suppressing treatment or infection.) c) Hemoglobin =/= 8.0 g/dL d) Total bilirubin < 1.5 times upper limit of normal (ULN) (unless due to Gilbert's Disease) e) Aspartate aminotransferase (AST; SGOT) and alanine aminotransferase (ALT; SGPT) < 2.5 times ULN or < 5x ULN if liver metastases are present f) Serum creatinine =/= 1.5 x ULN or creatinine clearance = 50 ml/min (either measured or estimated by the Cockcroft-Gault formula).
10) Females of childbearing potential must have a negative serum or urine pregnancy test within 3 days prior to initiating dosing. Male and female subjects with reproductive potential must agree to use appropriate contraceptive methods while on study therapy and for 84 days following their last dose of study medication.
11) The potential benefit of continued treatment with MT-3724 justifies the potential risks, and the potential risks are not unreasonable in the context of the subject’s NHL or CLL disease status.
12) Potential subjects must continue to meet the diagnostic criteria for B-Cell NHL that allowed them to be eligible for the MT-3724_NHL_001_US Phase I/Ib study.
1) Any limitation of the subject’s mental capacity such that the subject
cannot provide legal consent or understand information regarding the study.
2) Any condition (e.g., known or suspected poor compliance, psychological instability, geographical location, etc.) that, in the judgment of the Investigator, may affect the subject's ability to comply with all study procedures
3) Potential subjects with a history of another cancer other than basal cell carcinoma or cervical intraepithelial neoplasia (CIN; i.e., cervical cancer in situ) may not be enrolled unless: 1. the previous cancer was treated, 2. the patient has remained disease free for five or more years prior to screening, and 3. the patient is considered by their physician to be at less than 30% risk of relapse of this previous malignancy.
4) Potential subjects cannot have experienced a significant infection (CTCAE Grade 3 or 4 with or without neutropenia) within 2 weeks of initiating dosing in this protocol.
5) Ongoing use of any approved or investigational anti-neoplastic therapies are not allowed.
6) Potential subject may not be taking systemic corticosteroid therapy at a prednisone dose > 20mg/day (or equivalent) within 14 days prior to study enrollment
7) Potential subjects with pre-existing adverse events at screening that are severe or life threatening by Common Terminology Criteria for Adverse Events (CTCAE, v. 4.03) should not be enrolled. Serious complications of prior therapies or concomitant medical conditions which in the opinion of Investigator and/or Sponsor would make subject participation unsafe. This includes subjects who have had a systemic and/or hypersensitivity reaction to any other monoclonal antibody (MAb) or MAb fragment.
8) Potential subjects with uncontrolled or severe cardiovascular disease, including myocardial infarct or unstable angina within 6 months prior to study treatment, New York Heart Association (NYHA) Class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease, or cardiac amyloidosis that in the opinion of the Investigator would adversely affect study participation should not be enrolled.
9) Potential subjects with a significant history of renal (including hemolytic uremic syndrome), neurologic, psychiatric, endocrine, metabolic, immunologic, or hepatic disease that in the opinion of the Investigator would adversely affect study participation should not be enrolled. This includes potential subjects with a known history of drug abuse.
10) Potential subjects must not have received any vaccines for 14 days prior to administration of their first dose of MT-3724, at any time during the study or within 28 days after their last dose of MT 3724. The single exception to this exclusion is for the annual influenza (flu) vaccine. If, in the investigator’s judgment, a potential subject should receive the flu vaccine it may be given up to 7 days prior to the day of the first dose in any cycle in this study.
11) Potential subjects who are thought to have an allergy or sensitivity to MT-3724 or excipients based upon known allergies to compounds of a similar class, or whose past history suggests an increased potential for an adverse hypersensitivity reaction to MT-3724 (e.g.; prior anaphylactic or other severe infusion reactions to human immunoglobulin or MAb administration) should not be enrolled.
12) Potential subjects who are known seropositive for or have an active infection with human immunodeficiency virus (HIV-1 or HIV-2) are not eligible.
13) Potential subjects with known or clinically suspected hepatitis virus infection should not be enrolled. Specific serologic criteria are:Hepatitis A: potential subjects with known acute infection are excluded. Hepatitis B (HB): Potential subjects with the following known HB status ARE excluded: 1. Acutely infected: HBsAg positive, HBcAb positive (IgG + M), HBsAb negative 2. Chronically infected: HBsAg positive, HBcAb positive (IgG, not IgM), HBsAb negative 3. Interpretation unclear: HBsAg negative, HBcAb positive, HBsAb negative Potential subjects with the following known HB status ARE NOT excluded: 1. HB naïve - HBAg negative, HBcAb negative, HBsAb negative 2. Immune due to natural infection: HBsAg negative, HBcAb positive, HBsAb positive 3. Immune due to HB vaccination: HBsAg negative,, HBcAb negative, HBsAb positive
14) #14 Continued... Hepatitis C (HC) – potentials subjects who are known HCAb positive confirmed by HC-Recombinant immunoblot assay on the same sample are excluded. Hepatitis D – potential subjects with known past or present infection are not excluded unless co-infected with HB. If HB co-infection, refer to HB exclusion criteria. Hepatitis E - potential subjects with known past or present infection are excluded
15) Potential subjects and their partners, if either are of child-bearing potential, who will not comply with required birth control measures as described in Inclusion Criteria
16) Pregnant or breast feeding women
17) Potential subjects who have had major surgery within 6 weeks prior to the first dose of study drug or have major surgery planned during the first 12 weeks post MT-3724 exposure
Information and next steps
Michelle A. Fanale
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