Trial Title:
Polyspecific Antibodies in Lymphoproliferative T-cell Disorders
NCT ID:
NCT06495723
Condition:
Peripheral T Cells Lymphoma (PTCL)
Conditions: Official terms:
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Conditions: Keywords:
Relapsed Refractory PTCL
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
LIS1
Description:
The study intervention (LIS1) is a glyco-humanized polyclonal antibody drug which is
formulated for IV administration.
Arm group label:
Dose Escalation part: dose 2 mg/kg
Arm group label:
Dose Escalation part: dose 4 mg/kg
Arm group label:
Dose Escalation part: dose 6 mg/kg
Arm group label:
Expansion part
Summary:
This is a 2-part study consisting of a Part 1, dose escalation and dose-finding component
to establish the Maximal Tolerated Dose (MTD), or Recommended Part 2 Dose (RP2D) of LIS1
as a single agent; followed by a Part 2, to investigate anti-tumors efficacy of LIS1 in
selected subtypes of Peripheral TCell Lymphoma (PTCL) and to further evaluate its safety
and tolerability at RP2D.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Provide signed, written informed consent.
2. Is male or female, age ≥18 years old (at the time consent is obtained)
3. For Part 1: Has a histological diagnosis of the following relapsed or refractory
PTCL based on WHO 2022 classification of lymphoid neoplasms
- Intestinal T-cell and NK cell lymphoid proliferations and lymphomas (without NK
cell neoplasms)
- Hepatosplenic T-cell lymphoma
- Anaplastic large cell lymphoma
- Nodal TFH cell lymphoma
- Other peripheral t-cell lymphomas For Part 2: The type of PTCL will be defined
based on SC review after completion of Part 1 and will be documented in the
protocol amendment
4. Had previously received 1 or more appropriate systemic therapies, including an
alkylating agent and/or anthracycline, for treatment of the current disease
(radiation therapy alone would not be acceptable as previous therapy). Participants
with ALCL must have received prior brentuximab vedotin or be unable to receive it
due to allergy or intolerance.
5. Experienced disease progression during or after completion of most recent therapy or
refractory disease.
6. Has a measurable lesion by imaging: the longest diameter should be ≥1.5 cm for nodal
lesions and >1 cm for extra-nodal lesions.
7. Experienced a toxicity of prior therapy: Participants must have recovered to less
than Grade 1 or to baseline from toxicity of prior chemotherapy or biologic therapy
and must not have had major surgery, chemotherapy, radiation, or biologic therapy
within 2 weeks prior to beginning treatment.
Note: Exceptions to this include events not considered to place the participant at
unacceptable risk of participation in the opinion of the Investigator (e.g.,
alopecia).
8. Has either unstained tissues (block or unstained slides) or stained slides and
pathology report available for central review. If stained slides or unstained tissue
are not available or insufficient, a fresh tumor tissue sample is mandatory for
central pathology. Central pathology confirmation is not required prior to
enrollment.
9. Is able to provide a bone marrow aspirate and/or a biopsy no older than 3 months at
screening and agrees to undergo post-treatment bone marrow aspirate or biopsy when
required to confirm response.
10. Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
11. Has life expectancy of >3 months.
12. Has an adequate hematological and organ function at screening, including:
- Hemoglobin ≥8.0 g/dL (prior transfusion is acceptable)
- Absolute neutrophil count (ANC) ≥1000 cells/mm3 (without growth factor support
within 7 days of ANC measurement)
- Platelet count ≥50,000 cells/mm3 (without growth factor support or transfusion
within 7 days of platelets measurement)
- Creatinine clearance ≥30 mL/min
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <3 × the
upper limit of normal (ULN)
- Serum total bilirubin <2 × ULN OR <3 × ULN (for participants with Gilbert's
Syndrome)
13. Participants must be able to understand and sign an informed consent form.
14. All participants must use adequate contraception during participation in this study
and for 6 months following completing therapy.
Exclusion Criteria:
1. Is diagnosed with a bulky disease (≥10 cm).
2. Has known history or presence of central nervous system involvement by leukemia or
lymphoma.
3. Has Mature T-cell and NK-cell leukemias (WHO 2022 criteria)
4. Has T-lymphoblastic leukemia/lymphoma (WHO 2022 criteria)
5. Has tumor-like lesions with T-cell predominance (WHO 2022 criteria)
6. Has Primary cutaneous T-cell lymphomas (WHO 2022 criteria)
7. Has any other active cancers, or history of treatment for invasive cancer ≤3 years.
Note: Participants with stage I cancer who have received definitive local treatment
at least 3 years previously and are considered unlikely to recur are eligible. All
participants with previously treated in situ carcinoma (i.e., non-invasive) are
eligible.
8. Received any of the following treatments prior to the first dose of study
medication:
- Systemic chemotherapy, targeted small molecule therapy, or radiation therapy
within 4 weeks (or 5 half-lives, whichever is shorter) before Cycle 1 Day 1.
Participants that received local radiation therapy are eligible.
- Therapeutic anti-cancer antibodies <4 weeks
- Any investigational drug in the last 4 weeks prior
- Any major surgery or immunotherapy within 28 days
- Toxin immunoconjugates <4 weeks
- Nitrosoureas <6 weeks
- Allogeneic hematologic stem cell transplant within 3 months
- Adaptive cellular therapy such as autologous or donor natural killer cell or T
lymphocyte infusions within 90 days
- Systemic corticosteroids (prednisone or equivalent >10 mg daily) within 2 weeks
prior to the start of therapy, or 12 weeks if given to treat graft versus host
disease (GVHD), except for physiological replacement doses of cortisone acetate
or equivalent
- Systemic treatment for GVHD (including but not limited to oral or parenteral
corticosteroids, ibrutinib, and extracorporeal phototherapy) within the last 12
weeks
9. Is experiencing a toxicity (or AE) from prior anti-cancer treatment that has not
resolved to Grade ≤1 or baseline.
10. Has a known infection with human immunodeficiency virus (HIV) or serologic status
reflecting active hepatitis B or C infection as follows:
- Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody
(HBcAb). Participants with presence of HBcAb, but absence of HBsAg, are
eligible only if hepatitis B virus (HBV) DNA is undetectable by an assay with
sensitivity <20 IU/mL. If so, participants may either undergo regularly
scheduled monitoring of HBV DNA or less frequent monitoring of HBV DNA while on
prophylactic antiviral medication as defined by regional standard of care.
- Presence of hepatitis C virus (HCV) antibody. Participants with presence of HCV
antibody are eligible only if HCV RNA is undetectable.
11. Has a known active tuberculosis infection.
12. Has an active fungal, bacterial, and/or viral infection requiring systemic therapy.
13. Had a vaccination with a live vaccine within 35 days prior to the first dose of
LIS1.
14. If woman, is pregnant or nursing a child.
15. Has an active autoimmune disease or history of autoimmune disease that may relapse
except for type I diabetes under control, hypothyroidism managed with hormone
replacement therapy, controlled celiac disease, and skin disease (vitiligo,
psoriasis, etc.) not requiring systemic treatment.
16. Has a known history of interstitial lung disease, non-infectious pneumonitis,
pulmonary fibrosis, acute lung disease, or dyspnea at rest or pulse oxymetrie < 92%
at room air.
17. Has a clinically significant cardiovascular disease including the following:
- Myocardial infarction or unstable angina within 3 months before screening
- Congestive heart failure (New York Heart Association functional classification
III-IV)
- History of clinically significant arrythmias
- QTcF > 470 msec
- History of Mobitz II second degree or third-degree heart block without a
permanent pacemaker in place
- Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood
pressure measurements showing systolic blood pressure >170 mm Hg and diastolic
blood pressure >105 mmHg at screening
18. Has a cognitive impairment, active substance abuse, or psychiatric illness or social
situations that, in the view of the Investigator, would preclude safe treatment or
the ability to give informed consent and limit compliance with study requirements.
19. Has a known history of drug-induced liver injury, alcoholic liver disease, non-
alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic
obstruction caused by stones, cirrhosis of the liver or portal hypertension.
20. Has a hemophilia or von Willebrand's disease.
21. Has any psychological, familial, sociological, or geographical conditions that do
not permit compliance with the protocol.
22. Has a concurrent condition that, in the Investigator's opinion, would jeopardize
compliance with the protocol.
23. Are unable or unwilling to comply with study and/or follow-up procedures outlined in
the protocol.
24. For France, participants under legal protection (safeguard, guardianship,
curatorship).
25. Is currently participating in another therapeutic clinical study.
26. Has a known hypersensitivity to polyclonal antibody.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
CHU de Caen
Address:
City:
Caen
Zip:
14033
Country:
France
Status:
Recruiting
Contact:
Last name:
Gandhi-Laurent DAMAJ
Email:
damaj-gl@chu-caen.fr
Facility:
Name:
CHU de Clermont-Ferrand
Address:
City:
Clermont-Ferrand
Zip:
63003
Country:
France
Status:
Recruiting
Contact:
Last name:
Olivier TOURNILHAC, MD
Email:
otournilhac@chu-clermontferrand.fr
Facility:
Name:
CHU Henri-Mondor
Address:
City:
Créteil
Zip:
94000
Country:
France
Status:
Not yet recruiting
Contact:
Last name:
Françoise LEMONNIER, MD
Email:
francois.lemonnier@aphp.fr
Facility:
Name:
CHU de Bordeaux - GH Sud - Hôpital Haut-Lévêque
Address:
City:
Pessac
Zip:
33604
Country:
France
Status:
Recruiting
Contact:
Last name:
Kamal BOUABDALLAH
Email:
krimo.bouabdallah@chu-bordeaux.fr
Facility:
Name:
CHU de Lyon - Hôpital Lyon Sud
Address:
City:
Pierre-Bénite
Zip:
69310
Country:
France
Status:
Recruiting
Contact:
Last name:
Emmanuel BACHY
Email:
emmanuel.bachy@chu-lyon.fr
Start date:
July 9, 2024
Completion date:
July 31, 2027
Lead sponsor:
Agency:
Xenothera SAS
Agency class:
Industry
Source:
Xenothera SAS
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06495723
