A Phase 2/3 study to evaluate safety and efficacy of the combination of Bel- CHOP/ Fol-COP drugs against CHOP in newly diagnosed Peripheral T-Cell Lymphoma (blood cancer) patients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Acrotech Biopharma Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

26 Sep 2024 → ongoing

Decision date (initial)

2024-07-24

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Acrotech Biopharma Inc., 279 Princeton Hightstown Road, East Windsor, NJ 08520, United States

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacokinetic, Safety, Pharmacodynamic, Therapy, Dose response, Pharmacogenetic

• Part 1 (Dose Finding); Select which of the two dose levels for Belinostat and Pralatrexate associated with CHOP is best suitable for the Part 2 study based on safety and ORR at 3 months.
• Part 2 (Efficacy and Safety): To compare the PFS of patients with newly diagnosed PTCL treated for up to 6 cycles with Beleodaq (belinostat) in combination with CHOP (Bel-CHOP) or Folotyn (pralatrexate injection) in combination with COP (Fol-COP) to CHOP alone

Secondary objectives 1

1. • To compare the OS for patients with newly diagnosed PTCL treated with Bel-CHOP or Fol-COP to CHOP alone • To compare the ORR for patients with newly diagnosed PTCL treated with Bel-CHOP or Fol-COP to CHOP alone • Treatment compliance

Conditions and MedDRA coding

Peripheral T-Cell Lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. 1. Patient with newly diagnosed, untreated histology-proven PTCL based on local pathology review who is eligible for receiving Belinostat, Pralatrexate, and CHOP. Pathology material must be available at the site for each patient before enrollment so that it can be sent to the Sponsor (or designee) for later confirmation. The following subtypes, as defined by the updated WHO classification, may be included. This information should be available for eligibility: a. Pathology subtype: o Peripheral T-cell lymphoma, not otherwise specified o Angioimmunoblastic T-cell lymphoma o Anaplastic lymphoma kinase (ALK)-negative anaplastic large-cell lymphoma (ALCL) patients are eligible only if Brentuximab Vedotin (BV) is not commercially approved for use, not available in the country or patient is contraindicated to receive BV. o Follicular T-cell lymphoma o Others: Extra-nodal natural killer/T-cell lymphoma, nasal type; enteropathy-associated T-cell lymphoma; hepatosplenic T-cell lymphoma; and subcutaneous panniculitis-like T-cell lymphoma b. CD30 expression and T-cell Follicular Helper (TFH) phenotype status must be available for documentation. 2. Patient has at least 1 site of measurable disease according to Response Evaluation Criteria in Lymphoma (RECIL) 2017 criteria as assessed by local Investigator (Appendix 3) 3. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 4. For Part 1 (Dose Finding) - Patient has adequate hematological, hepatic, and renal function as defined by: a. Absolute neutrophil count ≥ 1.5 × 10⁹/L or ≥ 1.0 × 10⁹/L if evidence of bone marrow involvement b. Platelet count ≥100×10⁹/L or ≥ 75×10⁹/L if evidence of bone marrow involvement c. Total bilirubin ≤1.5 mg/dL d. Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤ 3×upper limit of normal (ULN; AST/ALT ≤5×ULN if documented hepatic involvement with lymphoma) e. Calculated creatinine clearance of ≥ 60 mL/min 5. Part 2 (Efficacy and Safety)- disease related hypoplasia, hepatological or renal dysfunction can be included if any of the treatment groups can be administered based on package insert recommendation with the following restrictions: a. Absolute neutrophil count ≥ 1.5 × 10⁹/L or ≥ 1.0 × 10⁹/L if evidence of bone marrow involvement b. Platelet count ≥100×10⁹/L or ≥ 75×10⁹/L if evidence of bone marrow involvement c. Total bilirubin ≤ 1.5 mg/dL d. Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT), alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤ 3 x the upper limit of normal (ULN; AST/ALT ≤5×ULN if documented hepatic involvement with lymphoma) e. Calculated creatinine clearance of ≥ 60 mL/min 6. UGT1A1 genotype has been characterized (see Belinostat dose modifications if abnormal) and must be available for documentation. 7. Patient must be willing and capable of giving written informed consent and must be able to adhere to dosing and visit schedules and meet all study requirements 8. Patient (male or female) is at least 18 years of age at the time of informed consent 9. Patient is willing to practice 2 forms of contraception, one of which must be a barrier method, from study entry until at least 6 months after the last dose of study treatment (Please refer to Appendix 4 for contraception guidance). 10. Females of childbearing potential must have a negative urine pregnancy test within 4 weeks prior to the first day of study treatment. Females who are postmenopausal for at least 1 year (defined as more than 12 months since last menses) or are surgically sterilized do not require this test. Please refer to Appendix 4 for further details.

Exclusion criteria 1

1. 1. Patients with a diagnosis of: a. Precursor T-cell lymphoma or leukemia b. Adult T-cell lymphoma/leukemia c. T-cell prolymphocytic leukemia d. T-cell large granular lymphocytic leukemia e. Primary cutaneous type ALCL f. Cutaneous T-cell lymphoma (mycosis fungoides/Sezary syndrome) g. ALCL if they can be treated with Brentuximab Vedotin (BV) 2) Patients taking drugs which are potent UGT1A1 inhibitors must discontinue one week before dosing before randomization; drug can be resumed if the treatment doesn’t include belinostat 3) Patient with an active concurrent malignancy/life-threatening disease with the exception of non-melanoma skin tumors and in situ cervical cancer if they have received treatment resulting in complete resolution of the cancer and currently have no clinical, radiologic, or laboratory evidence of active or recurrent disease. If there is a history of prior malignancies/life-threatening diseases, the patient must be disease free for at least 5 years 4) Prior HDAC inhibitor or pralatrexate therapy 5) Any known cardiac abnormalities such as baseline prolongation of QT/corrected QT (QTc) interval (ie, demonstration of a QTc interval >450 msec); long QT syndrome; myocardial infarction within 6 months prior to starting study; history of significant cardiovascular disease; the required use of a concomitant medication that may cause Torsades de Pointes 6) Patient with uncontrolled hypertension 7) Patients status on the following: a) Has a known HIV-positive diagnosis with uncontrolled and detectable viral load b) Has Hepatitis B or Hepatitis C virus diagnosis with uncontrolled and detectable viral load or immunological evidence of chronic active disease 8) Patient with central nervous system metastasis 9) Patient with an active uncontrolled infection, underlying medical condition, laboratory abnormality, or other serious illness that would impair the ability of the patient to receive protocol treatment 10) Patient who has used any investigational drugs, biologics, or devices within 28 days prior to study treatment or plans to use any of these during the course of the study 11) Patient with a known history of drug or alcohol abuse 12) Pregnant or breastfeeding women

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint is PFS, defined as the time (months) from randomization to the first documented PD or death, whichever occurs first.

Secondary endpoints 1

1. • Overall survival is defined as time from randomization to death due to any cause. Overall survival will be censored at the date patients were last known to be alive. • Objective response rate is defined as the percentage of patients who have a CR or PR as their best objective response. • Treatment compliance- Dose delays and reduction of the treatment arms will be evaluated.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Acrotech Biopharma Inc.

Sponsor organisation

Acrotech Biopharma Inc.

Address

279 Princeton Hightstown Road

City

East Windsor

Postcode

08520-1401

Country

United States

Scientific contact point

Organisation

Acrotech Biopharma Inc.

Contact name

Uma Srinivas Atmuri

Public contact point

Organisation

Acrotech Biopharma Inc.

Contact name

Uma Srinivas Atmuri

Third parties 7

Locations

5 EU/EEA countries · 36 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 45 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications