Trial Title:
To Evaluate Efficacy of Belinostat or Pralatrexate in Combination Against CHOP Alone in PTCL
NCT ID:
NCT06072131
Condition:
Peripheral T Cell Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Prednisone
Cyclophosphamide
Doxorubicin
Vincristine
Belinostat
Study type:
Interventional
Study phase:
Phase 3
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Intervention model description:
A Phase 3, Randomized, Open-Label Study Comparing the Efficacy and Safety of the
Combination of Beleodaq-CHOP or Folotyn-COP to the CHOP Regimen Alone in Newly Diagnosed
Patients with Peripheral T-Cell Lymphoma
Primary purpose:
Treatment
Masking:
None (Open Label)
Masking description:
None - Open Label
Intervention:
Intervention type:
Drug
Intervention name:
Belinostat Injection
Description:
Belinostat 600 mg/m2 or 1000 mg/m2 along with CHOP is given in each cycle
Arm group label:
Group 1a
Arm group label:
Group 1b
Other name:
Beleodaq®
Intervention type:
Drug
Intervention name:
Pralatrexate Injection
Description:
Pralatrexate 20 mg/m2 or 30 mg/m2 along with COP is given in each cycle
Arm group label:
Group 2a
Arm group label:
Group 2b
Other name:
Folotyn®
Intervention type:
Drug
Intervention name:
CHOP
Description:
CHOP is the comparator arm
Arm group label:
Group 1a
Arm group label:
Group 1b
Arm group label:
Group 3
Other name:
Cyclophosphamide, Hydroxydaunorubicin (doxorubicin), Oncovin (vincristine), and Prednisone
Intervention type:
Drug
Intervention name:
COP
Description:
COP is given in combination with Pralatrexate
Arm group label:
Group 2a
Arm group label:
Group 2b
Other name:
Cyclophosphamide, Oncovin (vincristine), and Prednisone
Summary:
Part 1: This is a 5 Arm study primarily to determine the best dose out of the two dose
levels of Belinostat and Pralatrexate combined with CHOP/COP in newly diagnosed PTCL
patients based on Safety for part 2 study.
Part 2 (Efficacy and Safety): This is a 3 Arm study. Patients with previously untreated
PTCL will be randomized 1:1:1 into 1 of 3 treatment groups: 2 experimental treatment
groups (Bel-CHOP or Fol-COP) or 1 active comparator treatment group (CHOP). Patients will
be treated for up to 6 cycles. The primary objective is to compare the Progression Free
Survival 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.
Detailed description:
Study Design and Treatment Plan:
Part 1: Dose Finding
It is a randomized, open label, multicenter study in patients with PTCL who have not been
previously treated and the control arm is CHOP, COP, is the CHOP regimen without
Doxorubicin (H). Two investigational agents are separately added to C(H)OP, Belinostat
for Bel-CHOP and Pralatrexate for FOL-COP. In this first part, each investigational arm
will have two dose levels which will be compared with CHOP as reference. Treatment will
be randomized in five arms:
1. Group 1a (Bel-CHOP) Belinostat 600 mg/m2
2. Group 1b (Bel-CHOP) Belinostat 1000 mg/m2
3. Group 2a (Fol-COP) Pralatrexate 20 mg/m2
4. Group 2b (Fol-COP) Pralatrexate 30 mg/m2
5. Group 3 for CHOP alone. Analysis will be done when 75 patients have received their
planned treatment cycles to evaluate treatment compliance.
Approximately 20 patients will be enrolled into each group and receive at least one cycle
of drug thus 15 patients are expected to be evaluated with their planned treatment of 6
cycles completed. The safety data will be evaluated to select the proper dose for
Belinostat -CHOP and Pralatrexate-COP for the Part 2 study.
Part 2: Efficacy and Safety
It is a randomized, open-label, multicenter study in newly diagnosed PTCL patients. This
is a three arm study and 143 patients will enroll in each arm. Patients will be
randomized in a balance manner (1:1:1) into 1 of 3 treatment groups and treated for up to
6 cycles:
Group 1: (Bel-CHOP): Belinostat at the dose determined from Part 1 (600 or 1000 mg/m2) to
be administered on Day 1 by 30 min intravenous (IV) infusion once daily for 5 days; CHOP
will also be administered starting on Day 1 within 15 min (±5 min) after the end of the
belinostat infusion at the doses shown below for Group 3, with cycles repeated every 21
days for up to 6 cycles
Group 2: (Fol-COP): Pralatrexate at the dose determined from part 1 (20 or 30 mg/m2) is
to be administered on Day 1 and Day 8 as an IV push over 3 to 5 min; CHOP will also be
administered starting on Day 1 within 15 min (±5 min) after the end of the pralatrexate
administration at the doses shown below for Group 3, with cycles repeated every 21 days
for up to 6 cycles. COP combination refers to CHOP without Doxorubicin (H).
Group 3: (CHOP): Combination chemotherapy to be administered starting on Day 1 at the
doses shown below, with cycles repeated every 21 days for up to 6 cycles
- Cyclophosphamide 750 mg/m2 IV, Day 1
- Doxorubicin 50 mg/m2 IV, Day 1 (limit lifetime cumulative dose to <550 mg/m² to
reduce risk of cardiotoxicity)
- Vincristine 1.4 mg/m2 (maximum 2 mg) IV, Day 1
- Prednisone 100 mg orally (PO) daily, Day 1 (after the end of the belinostat or
pralatrexate administration for Groups 1 and 2) to Day 5
Randomization will be stratified on:
- Histology (nodal, extra-nodal)
- Prognostic Index for T-Cell Lymphoma (Group 1 or 2 vs 3 or 4)
- Region (US, ex-US)
The study duration will include up to a 28-day screening period, a 6-cycle treatment
period (18 weeks), follow-up until progression, an End-of-Treatment Visit at least 30
days after the last dose of study treatment, and long-term survival follow-up for
patients by phone every 6 months thereafter until a 5-year median follow-up of the
population is reached. Patients discontinuing the study for other reasons than
progression will have the same long-term follow-up for OS analysis. Tumor assessments
will be performed every 3 cycles (i.e., 9 weeks) on Cycle 4 Day 1 and End-of-Treatment
Visit during treatment, then every 3 months for 3 years for patients with complete
response (CR), partial response (PR), or stable disease, and every 6 months thereafter
until disease progression or death
Criteria for eligibility:
Criteria:
Inclusion Criteria:
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 it can be sent to the Sponsor (or designee) for confirmation. The following
subtypes, as defined by the updated World Health Organization (WHO) classification,
may be included. This information should be available for eligibility:
1. Pathology subtype:
- Peripheral T-cell lymphoma, not otherwise specified
- Angioimmunoblastic T-cell lymphoma
- Anaplastic lymphoma kinase (ALK)- negative anaplastic large-cell lymphoma
(ALCL)
- Follicular T cell lymphoma
- 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
2. CD30 expression
3. TFH phenotype
2. Patient has at least 1 site of measurable disease according to Response Evaluation
Criteria in Lymphoma (RECIL) 2017 criteria as assessed by the local Investigator
(Appendix 3)
3. Patient has an Eastern Cooperative Oncology Group 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 b. Platelet count ≥100×109
- L 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×the upper limit of normal (ULN; AST/ALT
≤5×ULN if documented hepatic involvement with lymphoma) e. Serum creatinine
≤2.0×ULN or 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:
1. Absolute neutrophil count ≥1.0×109/L or >= ≥1.5×109/L if bone marrow
involvement
2. Platelet count ≥100×109
- L or ≥75×109
- L if bone marrow involvement
3. Total bilirubin ≤1.5 mg/dL
4. Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase
(SGOT), alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase
(SGPT) ≤3×the upper limit of normal (ULN; AST/ALT ≤5×ULN if documented hepatic
involvement with lymphoma)
5. Serum creatinine ≤2.0×ULN
6. Calculated creatinine clearance of ≥60 mL/min
6. UGT1A1 genotype has been characterized (see Belinostat dose modifications if
abnormal).
7. A decision whether to use prophylactic growth factor for cycle 1 or not has been
made
8. 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
9. Patient (male/female) is at least 18 years of age at the time of informed consent
10. Patient is willing to practice 2 forms of contraception, one of which must be a
barrier method, from study entry until at least 30 days after the last dose of study
treatment
11. 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
Exclusion Criteria:
1. Patients with a diagnosis of:
1. Precursor T-cell lymphoma or leukemia
2. Adult T-cell lymphoma/leukemia
3. T-cell prolymphocytic leukemia
4. T-cell large granular lymphocytic leukemia
5. Primary cutaneous type ALCL
6. Cutaneous T-cell lymphoma (mycosis fungoides/Sezary syndrome)
7. ALCL except if Brentuximab Vendotin cannot be utilized
2. Patients taking drugs which are potent UGT1A1 inhibitors must discontinue one week
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 histone deacetylase (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 with a known HIV-positive diagnosis, hepatitis B virus or hepatitis C virus
diagnosis with 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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of California, San Francisco Fresno
Address:
City:
Clovis
Zip:
93611
Country:
United States
Status:
Recruiting
Contact:
Last name:
Joseph Mosholder
Email:
JMosholder@communitymedical.org
Contact backup:
Last name:
Richard Ward
Phone:
5593871828
Email:
RWard5@communitymedical.org
Investigator:
Last name:
Haifaa Abdulhaq, MD
Email:
Principal Investigator
Facility:
Name:
David Geffen School of Medicine at University of California, Los Angeles
Address:
City:
Los Angeles
Zip:
90095
Country:
United States
Status:
Recruiting
Contact:
Last name:
Vanessa Crowell
Email:
VCrowell@mednet.ucla.edu
Contact backup:
Last name:
Rosa Bishop
Email:
RBishop@mednet.ucla.edu
Investigator:
Last name:
Herbert Eradat, MD
Email:
Principal Investigator
Facility:
Name:
Moffitt Malignant Hematology & Cellular Therapy at Memorial Healthcare System Memorial Cancer Institute
Address:
City:
Pembroke Pines
Zip:
33026
Country:
United States
Status:
Recruiting
Contact:
Last name:
Andres Alvarez
Phone:
954-265-4325
Email:
andralvarez@mhs.net
Investigator:
Last name:
Jose Sandoval Sus, MD
Email:
Principal Investigator
Facility:
Name:
Norton Cancer Institute
Address:
City:
Louisville
Zip:
40207
Country:
United States
Status:
Recruiting
Contact:
Last name:
Jason Beare
Phone:
502-629-5756
Email:
Jason.Beare@nortonhealthcare.org
Investigator:
Last name:
Don Stevens, MD
Email:
Principal Investigator
Facility:
Name:
Rutgers Cancer Institute of New Jersey
Address:
City:
New Brunswick
Zip:
08901
Country:
United States
Status:
Recruiting
Contact:
Last name:
Kassie DiOrio
Phone:
732-235-2135
Email:
kassie.diorio@rutgers.edu
Investigator:
Last name:
Yun Kyuong (Claire) Tiger, MD
Email:
Principal Investigator
Facility:
Name:
Valley Cancer Associates
Address:
City:
Harlingen
Zip:
78550
Country:
United States
Status:
Withdrawn
Facility:
Name:
University of Texas, MD Anderson Cancer Center
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Last name:
Vaishnavi Vutukuri
Phone:
713-792-5242
Email:
VVutukuri@mdanderson.org
Investigator:
Last name:
Swaminathan P Iyer, MD
Email:
Principal Investigator
Facility:
Name:
Baylor Scott & White Medical Center - Temple
Address:
City:
Temple
Zip:
76508
Country:
United States
Status:
Recruiting
Contact:
Last name:
Lorie Fares
Phone:
254-724-1395
Email:
Lorie.Fares@BSWHealth.org
Investigator:
Last name:
Archana Sagar, MD
Email:
Principal Investigator
Facility:
Name:
Semmelweis Egyetem
Address:
City:
Budapest
Zip:
1088
Country:
Hungary
Status:
Recruiting
Contact:
Last name:
Zsolt Nagy
Phone:
36-20-8 258 660
Email:
nagy.zsolt@med.semmelweis-univ.hu
Investigator:
Last name:
Zsolt Nagy, MD
Email:
Principal Investigator
Facility:
Name:
Inje University Busan Paik Hospital
Address:
City:
Busan
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Won-Sik Lee, MD
Phone:
82-51-890-6407
Email:
wonsik112@gmail.com
Investigator:
Last name:
Won-Sik Lee, MD
Email:
Principal Investigator
Facility:
Name:
Ulsan University Hospital
Address:
City:
Ulsan
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Jae-cheol Jo, MD
Phone:
82-52-2508632
Email:
jcjo@ulsan.ac.kr
Investigator:
Last name:
Jae-cheol Jo, MD
Email:
Principal Investigator
Facility:
Name:
Ajou University Hospital
Address:
City:
Suwon-si
Zip:
16499
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Sumi Kim
Phone:
82312195489
Email:
ajouhema@gmail.com
Investigator:
Last name:
Seong Hyun Jeong, MD
Email:
Principal Investigator
Facility:
Name:
The Catholic University of Korea - St. Vincents Hospital
Address:
City:
Suwon-si
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
EunJin Lee, MD
Phone:
82-31-249-8456
Email:
i-ej@daum.net
Contact backup:
Last name:
Jin Ah Kim
Email:
jina10206@hanmail.net
Investigator:
Last name:
Jeong-A Kim, MD
Email:
Principal Investigator
Facility:
Name:
Gyeongsang National University Hospital
Address:
City:
Jinju-si
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Hyeran Lee
Email:
hyehyer2@gmail.com
Investigator:
Last name:
Gyeong-Won Lee, MD
Email:
Principal Investigator
Facility:
Name:
Jeonbuk National University Hospital
Address:
City:
Jeonju
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Jae-Yong Kwak, MD
Phone:
82-63-2501791
Email:
jykwak@jbnu.ac.kr
Investigator:
Last name:
Jae-Yong Kwak, MD
Email:
Principal Investigator
Facility:
Name:
Yeungnam University Medical Center
Address:
City:
Daegu
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Min Kyoung Kim, MD
Phone:
53-620-4683
Email:
kmk21c@medical.yu.ac.kr
Investigator:
Last name:
Min Kyoung Kim, MD
Email:
Principal Investigator
Facility:
Name:
Asan Medical Center
Address:
City:
Songpa-dong
Zip:
05505
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
HaYoung Lee
Phone:
82-2-3010-5001
Email:
youngct0818@amc.seoul.kr
Investigator:
Last name:
Dok Hyun Yoon, MD
Email:
Principal Investigator
Investigator:
Last name:
Hyungwoo Cho, MD
Email:
Sub-Investigator
Investigator:
Last name:
Jaewon Hyung, MD
Email:
Sub-Investigator
Facility:
Name:
Daegu Catholic University Medical Center
Address:
City:
Daegu
Zip:
42472
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Na Rae Chun
Phone:
82536503251
Email:
cnr042611@dcmc.co.kr
Investigator:
Last name:
Sung Hwa Bae, MD
Email:
Principal Investigator
Investigator:
Last name:
Yun hui Hwang, MD
Email:
Sub-Investigator
Facility:
Name:
Samsung Medical Center
Address:
City:
Seoul
Zip:
6351
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Won-Seog Kim, MD
Phone:
82-2-3410-6548
Email:
wonseog.kim@samsung.com
Investigator:
Last name:
Won-seog Kim, MD
Email:
Principal Investigator
Facility:
Name:
Seoul National University Hospital
Address:
City:
Seoul
Country:
Korea, Republic of
Status:
Recruiting
Contact:
Last name:
Eun Hee Park
Phone:
82-22-0727217
Email:
eh.park@daum.net
Investigator:
Last name:
Yougil Koh, MD
Email:
Principal Investigator
Facility:
Name:
Pratia MCM Krakow
Address:
City:
Krakow
Zip:
30-727
Country:
Poland
Status:
Recruiting
Contact:
Last name:
Karolina Magielska
Phone:
+48 723 995 230
Email:
karolina.magielska@pratia.com
Contact backup:
Last name:
Magdalena Majdanska
Email:
Magdalena.Majdanska@pratia.com
Investigator:
Last name:
Wojciech Jurczak, MD
Email:
Principal Investigator
Facility:
Name:
Changhua Christian Hospital CCH
Address:
City:
Changhua City
Country:
Taiwan
Status:
Recruiting
Contact:
Last name:
Ai-Ping Lai
Phone:
+886 4 723 8595
Email:
96953@cch.org.tw
Contact backup:
Last name:
Ya-Tzu Chen
Phone:
+886 4 723 8595
Investigator:
Last name:
Hsuan-Yu Lin, MD
Email:
Principal Investigator
Facility:
Name:
Hualien Tzu Chi Medical Center
Address:
City:
Hualien City
Zip:
970
Country:
Taiwan
Status:
Recruiting
Contact:
Last name:
Mei-Ru Chen
Phone:
+88638561825
Phone ext:
17601
Email:
lindachen@tzuchi.com.tw
Contact backup:
Last name:
Ming-Fen Wu
Phone:
+88638561825
Phone ext:
17602'
Email:
mfwu@tzuchi.com.tw
Investigator:
Last name:
Sheng-Chuan Huang, MD
Email:
Principal Investigator
Facility:
Name:
National Cheng Kung University Hospital NCKUH
Address:
City:
Tainan City
Zip:
704
Country:
Taiwan
Status:
Recruiting
Contact:
Last name:
Ya-Zong Hsu
Phone ext:
886-6-2353535
Email:
yzhsu1035@gmail.com
Contact backup:
Last name:
Hsiang-Lien Li
Phone:
886-6-2353535
Phone ext:
3974
Email:
james513250@gmail.com
Investigator:
Last name:
Ya-Ting Hsu, MD
Email:
Principal Investigator
Facility:
Name:
Chang Bing Show Chwan Memorial Hospital
Address:
City:
Changhua
Country:
Taiwan
Status:
Recruiting
Contact:
Last name:
Cheng-Shyong Chang, MD
Phone:
886-4-7381888
Email:
cs4816@gmail.com
Investigator:
Last name:
Cheng-Shyong Changs, MD
Email:
Principal Investigator
Facility:
Name:
Hematology Oncology Taipei Medical University - Shuang-Ho Hospital
Address:
City:
New Taipei City
Country:
Taiwan
Status:
Recruiting
Contact:
Last name:
Tsu Yi Chao, MD
Phone:
886-2-22490088
Email:
10575@s.tmu.edu.tw
Investigator:
Last name:
Tsu Yi Chao, MD
Email:
Principal Investigator
Start date:
October 4, 2023
Completion date:
November 2030
Lead sponsor:
Agency:
Acrotech Biopharma Inc.
Agency class:
Industry
Source:
Acrotech Biopharma Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06072131
