Overview
Pharmacokinetics (PK), Pharmacodynamics (PD), Safety, Tolerability of Multiple Dose Regimens of MT-3724 for the Treatment of Patients With Relapsed Chronic B-cell Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Status:
Withdrawn
Withdrawn
Trial end date:
2016-12-01
2016-12-01
Target enrollment:
0
0
Participant gender:
All
All
Summary
This Phase I, multiple ascending dose study will seek to enroll subjects with relapsed/refractory Chronic B-cell Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) with confirmed and measurable disease who have received standard treatment with at least one anti-CD20 antibody (e.g.; rituximab, ofatumumab) containing front-line regimen that resulted in initial response, followed by relapse/recurrence and who are not eligible for any further approved biologic therapy, chemotherapy and/or autologous stem transplantation and/or refuse alternative approved therapies and/or are unlikely to achieve clinical benefit from any therapy of higher priority by Investigator assessment.Phase:
Phase 1Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
Molecular Templates, Inc.
Criteria
Inclusion Criteria:- Men or women, age 18 years or older
- Life expectancy > 3 months
- Flow cytometric confirmation of CLL is required at screening. Previous confirmation of
CLL/SLL including confirmed immunohistological diagnosis with a characteristic
CD5+/CD20+ B-cell immunophenotype according to WHO criteria
- For CLL: a. An absolute peripheral blood monoclonal CD20+/CD5+ B-lymphocyte count >
5000/μL for the duration of at least 3 months
- For SLL: An absolute peripheral blood monoclonal CD20+/CD5+ B-lymphocyte count <
5000/μL AND Presence of lymphadenopathy and/or splenomegaly, with histopathological
evaluation of a lymph node biopsy consistent with CLL/SLL.
- Staging CLL: Rai Stage III or IV disease, or stage 0-II disease that meets NCIWG
criteria for active disease requiring therapy; SLL: Intermediate or high risk by Ann
Arbor Staging with Cotswald Modifications that meets criteria for active disease
requiring therapy.
- Relapsed/ Refractory CLL/SLL that has progressed despite treatment with all approved
therapies known to provide clinical benefit for their disease and for which the
potential subject is eligible or the potential subject must have refused any other
available approved treatment options prior to consideration for enrollment.
- Potential subjects must have received at least one anti-CD20 antibody containing
regimen in the past that resulted in initial measurable response (partial or complete
remission), followed by relapse/recurrence.
- Potential subjects for which high-dose chemotherapy and autologous stem cell
transplantation (HD-ASCT) is considered a standard curative therapy are eligible for
this study if the potential subject's disease has relapsed after HD-ASCT, or the
potential subject is not eligible for HD-ASCT or the potential subject has refused
HD-ASCT.
- Potential subjects who have had HD-ASCT must be at least 26 weeks beyond transplant.
- All potential subjects are required to have measurable disease following previous
therapy for CLL/SLL. Measurable disease, as determined by NCI-WG criteria, following
standard first-line or salvage therapy; this includes potential subjects with
progressive disease (PDs), stable disease (SDs), or partial remission (PR) and/or
Residual disease as determined by measurable disease (i.e., PDs, SDs, or PR) or by MRD
positivity, determined by flow cytometry of bone marrow and/or peripheral blood (see
Laboratory Manual) in potential subjects with Complete Response (CR) or CR with
incomplete bone marrow recovery (CRi) (previously termed "nodular partial remission"
[(nPR])
- Eastern Cooperative Oncology Group (ECOG) performance status of < 2.
- Patients must be at least 28 days past their last course of leukemia or lymphoma
treatment and have recovered from side effects of such therapy completely or with only
minor residual symptoms including any significant laboratory. Patients with
pre-existing severe or life threatening side effects/conditions from prior therapy or
due to other diseases may not be enrolled
- Female patients 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 acceptable contraceptive methods while on
study therapy and for 12 week following their last dose of study medication.
Exclusion Criteria:
- Ongoing use of any approved or investigational anti-neoplastic therapies with the
exceptions of ongoing hormonal therapy for breast cancer (without evidence of active
disease) or prostate cancer (stable on hormonal therapy).
- History of an absolute anti-CD20 monoclonal antibody (MAb) refractory CLL/SLL, defined
as a failure to have ever achieved a PR, CR with persistent lymphocytic nodules in the
marrow ("nPR"), or CR for at least 6 months in response to at least one anti-CD20
MAb-containing regimen amongst all past CLL/SLL treatments.
- Potential subjects cannot have experienced a significant (CTCAE Grade 3 or 4 with or
without neutropenia) infection within 2 weeks of the first dose of MT-3724.
- Patients who cannot comply with protocol requirements including clinic visits for
intravenous infusions and birth control measures may not be enrolled.
- Female patients who are pregnant or are breast feeding.
- Patients are not eligible if they are using any other approved or investigational
anti-neoplastic therapies or any other investigational therapies for any other reason.
- Patients may not be receiving systemic corticosteroid therapy at a prednisone dose >
20 mg/day (or steroid equivalent) within 2 weeks of starting study.
- Patients with uncontrolled or severe cardiovascular disease, including myocardial
infarct or unstable angina within 6 months prior to start of 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 may not be enrolled.
- Patients with a known history of drug abuse or any chronic neurologic, psychiatric,
endocrine, metabolic, immunologic, hepatic or renal disease (including a history of
hemolytic uremic syndrome) that in the opinion of the Investigator would adversely
affect study participation.
- Patients with known active Hepatitis C, HIV or a present history of Hepatitis B
- Patients must not have received any vaccines for 28 days prior to administration of
their first dose of MT-3724 and should not receive any vaccine during the study or
within 28 days after their last dose of MT-3724.
- Patients with a suspected allergy or sensitivity to any component of MT-3724 drug
preparation based upon known allergies to compounds of a similar class who have had an
anaphylactic or other severe infusion reaction to human immunoglobulin or monoclonal
antibody administration are not eligible.
- Potential subjects who have undergone allogeneic hematopoietic stem cell transplant or
any solid organ transplant.
- Autologous hematopoietic stem cell transplant within 26 weeks prior to study entry;
any history of allogeneic hematopoietic stem cell transplant.