Trial Title:
Tegavivint for Treating Patients With Relapsed or Refractory Large B-Cell Lymphoma
NCT ID:
NCT05755087
Condition:
Recurrent Diffuse Large B-Cell Lymphoma Activated B-Cell Type
Recurrent Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type
Recurrent High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements
Recurrent High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements
Refractory Diffuse Large B-Cell Lymphoma Activated B-Cell Type
Refractory Diffuse Large B-Cell Lymphoma Germinal Center B-Cell Type
Refractory High Grade B-Cell Lymphoma With MYC and BCL2 or BCL6 Rearrangements
Refractory High Grade B-Cell Lymphoma With MYC, BCL2, and BCL6 Rearrangements
Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Recurrence
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (Tegavivint)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT
Arm group label:
Treatment (Tegavivint)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Procedure
Intervention name:
Positron Emission Tomography
Description:
Undergo PET scan
Arm group label:
Treatment (Tegavivint)
Other name:
Medical Imaging, Positron Emission Tomography
Other name:
PET
Other name:
PET Scan
Other name:
Positron Emission Tomography Scan
Other name:
Positron-Emission Tomography
Other name:
proton magnetic resonance spectroscopic imaging
Other name:
PT
Intervention type:
Drug
Intervention name:
Tegavivint
Description:
Given IV
Arm group label:
Treatment (Tegavivint)
Other name:
BC 2059
Other name:
BC-2059
Other name:
BC2059
Other name:
Tegatrabetan
Summary:
This phase I trial tests the safety, side effects, and best dose of tegavivint in
treating patients with large b-cell lymphomas that has come back (relapsed) or does not
respond to treatment (refractory). Tegavivint may stop the growth of cancer cells by
blocking some of the enzymes needed for cell growth. Giving tegavivint may help control
the disease.
Detailed description:
PRIMARY OBJECTIVES:
I. To determine the safety and tolerability of tegavivint in patients with
relapsed/refractory c-Myc overexpressing large B-cell lymphoma.
II. To determine the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) of
tegavivint.
SECONDARY OBJECTIVES:
I. To determine the preliminary efficacy of tegavivint in patients with
relapsed/refractory c-Myc overexpressing large B-cell lymphoma.
II. To determine the pharmacokinetic parameters of tegavivint.
EXPLORATORY OBJECTIVES:
I. To correlate response to tegavivint with the presence of MYC, FBW7 and SKP2 mutations.
II. To correlate response to tegavivint with TBL1 and c-Myc expression assessed by
standard IHC on archived tumor biopsy.
III. To determine the effects of tegavivint on immune cell subsets viability and
function.
OUTLINE: This is a dose-escalation study of tegavivint.
Patients receive tegavivint intravenously (IV) on study. Patients also undergo computed
tomography (CT) and/or positron emission tomography (PET) and undergo blood sample
collection throughout the trial.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
One of the following three conditions:
- Relapsed/refractory histologically confirmed germinal center B-cell-like (GCB) and
non-GCB diffuse large B cell lymphoma (DLBCL) with the following features:
- Increased expression of MYC (>= 40%) and BCL2 (>= 50%) by immunohistochemistry
(IHC) or
- Presence of isolated MYC translocation Or
- Relapsed/refractory histologically confirmed high-grade B-cell lymphoma (HGBCL)
(double hit [DH] and triple hit [TH]) with translocations of MYC and BCL2 and/or
BCL6 Or
- Histologic transformation of indolent non-Hodgkin's lymphoma (NHL) to DLBCL
- Presence of BCL2 translocation with increased expression of MYC (≥40%) with or
without MYC translocation
- Patients must have had at least two prior systemic therapies
- Patients must be ineligible for or refused autologous or allogenic hematopoietic
stem cell transplantation or chimeric antigen receptor (CAR) T-cell therapy. Prior
autologous stem cell transplant and/or CAR-T are allowed, if received >= 3 months
prior to enrollment
- Age >= 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- Patients must have radiographically measurable disease by standard positron emission
tomography (PET) uptake with at least one site of measured disease by standardized
uptake value (SUV)
- Absolute neutrophil count (ANC) > 1,000/mcL
- Platelet count > 75,000/mcL
- Total bilirubin =< 1.5 x the upper limit of the normal range (ULN)
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < 3 x institutional
ULN
- Creatinine clearance >= 60 ml/min by Cockcroft-Gault (actual body weight will be
used to estimate creatinine clearance)
- Patients must be willing and able to understand and give written informed consent
and comply with all study related procedures
- Women of child-bearing potential (WOCBP) and men who are sexually active with WOCBP
must agree to use one hormonal contraceptive (e.g. combined oral contraceptives,
patch, vaginal ring, injectables, and implants); intrauterine device (IUD) or
intrauterine system (IUS); vasectomy or tubal ligation; and one effective method of
contraception, including male condom, female condom, cervical cap, diaphragm or
contraceptive sponge or abstain from sex for the duration of study participation and
for 4 months following completion of tegavivint administration. Should a woman
become pregnant or suspect she is pregnant while she or her partner is participating
in this study, she should inform her treating physician immediately.
Contraception includes:
- Total abstinence (when this is in line with the preferred and usual lifestyle of the
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal,
post-ovulation methods) and withdrawal are not acceptable methods of contraception
- Female sterilization (have had surgical bilateral oophorectomy with or without
hysterectomy), total hysterectomy or tubal ligation at least 6 weeks before taking
study treatment. In case of oophorectomy alone, only when the reproductive status of
the woman has been confirmed by follow up hormone level assessment
- Male sterilization (at least 6 months prior to screening). For female patients on
the study the vasectomized male partner should be the sole partner for that patient
- Use of oral (estrogen and progesterone), injected or implanted combined hormonal
methods of contraception or placement of an intrauterine device (IUD) or
intrauterine system (IUS) or other forms of hormonal contraception that have
comparable efficacy (failure rate <1%), for example hormone vaginal ring or
transdermal hormone contraception
- Sexually active males must use a condom during intercourse while taking drug and for
4 months after stopping study treatment and should not father a child in this
period. A condom is required to be used also by vasectomized men in order to prevent
delivery of the drug via seminal fluid In case of use of oral contraception women
should have been stable on the same pill for a minimum of 3 months before taking
study treatment. Women are considered post-menopausal and not of child bearing
potential if they have had 12 months of natural (spontaneous) amenorrhea with an
appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms)
or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal
ligation at least 6 weeks ago. In the case of oophorectomy alone, only when the
reproductive status of the woman has been confirmed by follow up hormone level
assessment is she considered not of child bearing potential
Exclusion Criteria:
- History of allergic reactions attributed to compounds of similar chemical or
biologic composition to tegavivint or other agents used in study
- Known active central nervous system (CNS) lymphoma, history of CNS involvement
allowed if in remission for >= 3 months
- Evidence of chronic active Hepatitis B, chronic active Hepatitis C infection
- Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral
therapy (e.g., strong CYP3A inhibitors and/or concomitant medications that are
excluded) are ineligible because of the potential for pharmacokinetic interactions
with tegavivint
- Known history of active TB (Bacillus Tuberculosis)
- Major surgery within 3 weeks prior to start of study treatment
- Clinically significant, uncontrolled heart disease and/or cardiac repolarization
abnormality or corrected QT interval (QTc) > 480 msec
- Uncontrolled concurrent illness including, but not limited to: ongoing or active
infection (Viral, bacterial, fungal or other)
- Psychiatric illness/social situations that would limit compliance with study
requirements
- Pregnant and breastfeeding women are excluded from this study. The effects of
tegavivint on the developing human fetus have the potential for teratogenic or
abortifacient effects. There is an unknown but potential risk for adverse events in
nursing infants secondary to treatment of the mother with tegavivint
- Patients with abnormal serum chemistry values other than the specific limits
detailed above, that in the opinion of the investigator is considered to be
clinically significant, should be discussed with the Study PI before being enrolled
in the study
- Personal history of malignancy except:
- Cervical intraepithelial neoplasia;
- Skin basal cell carcinoma;
- Treated localized prostate carcinoma with prostate specific antigen (PSA) <1
ng/mL or untreated indolent prostate cancer
- Neoplasia treated with curative intent, in remission for at least three years
and considered at low risk of relapse
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Ohio State University Comprehensive Cancer Center
Address:
City:
Columbus
Zip:
43210
Country:
United States
Status:
Recruiting
Contact:
Last name:
Lapo Alinari, MD, PhD
Phone:
614-293-5594
Email:
Lapo.Alinari@osumc.edu
Investigator:
Last name:
Lapo Alinari, MD, PhD
Email:
Principal Investigator
Start date:
March 6, 2023
Completion date:
March 5, 2027
Lead sponsor:
Agency:
Lapo Alinari
Agency class:
Other
Source:
Ohio State University Comprehensive Cancer Center
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05755087
http://cancer.osu.edu
