To Evaluate Efficacy of Belinostat or Pralatrexate in Combination Against CHOP Alone in PTCL (CRESCENDO)
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ClinicalTrials.gov Identifier: NCT06072131 |
Recruitment Status :
Recruiting
First Posted : October 10, 2023
Last Update Posted : February 7, 2024
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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.
Condition or disease | Intervention/treatment | Phase |
---|---|---|
Peripheral T Cell Lymphoma | Drug: Belinostat Injection Drug: Pralatrexate Injection Drug: CHOP Drug: COP | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 504 participants |
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 |
Masking: | None (Open Label) |
Masking Description: | None - Open Label |
Primary Purpose: | Treatment |
Official Title: | 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 |
Actual Study Start Date : | October 4, 2023 |
Estimated Primary Completion Date : | July 2030 |
Estimated Study Completion Date : | November 2030 |
Arm | Intervention/treatment |
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Active Comparator: Group 1a
Group 1a Belinostat 600 mg/m2 + CHOP
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Drug: Belinostat Injection
Belinostat 600 mg/m2 or 1000 mg/m2 along with CHOP is given in each cycle
Other Name: Beleodaq® Drug: CHOP CHOP is the comparator arm
Other Name: Cyclophosphamide, Hydroxydaunorubicin (doxorubicin), Oncovin (vincristine), and Prednisone |
Active Comparator: Group 1b
Group 1b Belinostat 1000 mg/m2 + CHOP
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Drug: Belinostat Injection
Belinostat 600 mg/m2 or 1000 mg/m2 along with CHOP is given in each cycle
Other Name: Beleodaq® Drug: CHOP CHOP is the comparator arm
Other Name: Cyclophosphamide, Hydroxydaunorubicin (doxorubicin), Oncovin (vincristine), and Prednisone |
Active Comparator: Group 2a
Group 2a Pralatrexate 20 mg/m2 + COP
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Drug: Pralatrexate Injection
Pralatrexate 20 mg/m2 or 30 mg/m2 along with COP is given in each cycle
Other Name: Folotyn® Drug: COP COP is given in combination with Pralatrexate
Other Name: Cyclophosphamide, Oncovin (vincristine), and Prednisone |
Active Comparator: Group 2b
Group 2b Pralatrexate 30 mg/m2 + COP
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Drug: Pralatrexate Injection
Pralatrexate 20 mg/m2 or 30 mg/m2 along with COP is given in each cycle
Other Name: Folotyn® Drug: COP COP is given in combination with Pralatrexate
Other Name: Cyclophosphamide, Oncovin (vincristine), and Prednisone |
Active Comparator: Group 3
CHOP
|
Drug: CHOP
CHOP is the comparator arm
Other Name: Cyclophosphamide, Hydroxydaunorubicin (doxorubicin), Oncovin (vincristine), and Prednisone |
- PFS [ Time Frame: 4.5 years ]Progression-free survival is determined from randomization to the first documented Progression of Disease or death, whichever occurs first.
- Overall survival [ Time Frame: 8 years ]It is the time from randomization to the death
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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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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:
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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
- CD30 expression
- TFH phenotype
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- 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)
- Patient has an Eastern Cooperative Oncology Group performance status ≤2
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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
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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:
- Absolute neutrophil count ≥1.0×109/L or >= ≥1.5×109/L if bone marrow involvement
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Platelet count ≥100×109
- L or ≥75×109
- L if bone marrow involvement
- Total bilirubin ≤1.5 mg/dL
- 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)
- Serum creatinine ≤2.0×ULN
- Calculated creatinine clearance of ≥60 mL/min
- UGT1A1 genotype has been characterized (see Belinostat dose modifications if abnormal).
- A decision whether to use prophylactic growth factor for cycle 1 or not has been made
- 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
- Patient (male/female) is at least 18 years of age at the time of informed consent
- 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
- 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:
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Patients with a diagnosis of:
- Precursor T-cell lymphoma or leukemia
- Adult T-cell lymphoma/leukemia
- T-cell prolymphocytic leukemia
- T-cell large granular lymphocytic leukemia
- Primary cutaneous type ALCL
- Cutaneous T-cell lymphoma (mycosis fungoides/Sezary syndrome)
- ALCL except if Brentuximab Vendotin cannot be utilized
- 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
- 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
- Prior histone deacetylase (HDAC) inhibitor or pralatrexate therapy
- 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
- Patient with uncontrolled hypertension
- 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
- Patient with central nervous system metastasis
- 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
- 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
- Patient with a known history of drug or alcohol abuse
- Pregnant or breastfeeding women
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT06072131
Contact: Uma Srinivas Atmuri, MPharm, MS | 732-917-2420 | uatmuri@acrotechbiopharma.com |
United States, New Jersey | |
Rutgers Cancer Institute of New Jersey | Recruiting |
New Brunswick, New Jersey, United States, 08901 | |
Contact: Kassie DiOrio 732-235-2135 kassie.diorio@rutgers.edu | |
United States, Texas | |
Valley Cancer Associates | Recruiting |
Harlingen, Texas, United States, 78550 | |
Contact: Elyssa Navarro 956-608-6719 |
Study Director: | Uma Srinivas Atmuri, MPharm, MS | Acrotech Biopharma Inc. |
Responsible Party: | Acrotech Biopharma Inc. |
ClinicalTrials.gov Identifier: | NCT06072131 |
Other Study ID Numbers: |
SPI-Bel-301 Study 70,789 ( Other Identifier: FDA ) |
First Posted: | October 10, 2023 Key Record Dates |
Last Update Posted: | February 7, 2024 |
Last Verified: | February 2024 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Plan Description: | Data Review Committee: An Independent Data Monitoring Committee (IDMC) will be established for the purpose of reviewing patient safety and the results of the futility analysis. The IDMC will convene after the enrollment and analysis of Part 1 to evaluate safety and preliminary efficacy. The IDMC will recommend the selected dose for Belinostat and Pralatrexate. The IDMC will also convene after the analysis of 120 events, in Part 2, to state whether the study can continue. This Committee will review review study data will adjudicate tumor response and the date of onset of disease progression in all patients at the end of the study. All scans will be centrally reviewed and the primary analysis of PFS will be conducted on these results. |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Lymphoma Lymphoma, T-Cell Lymphoma, T-Cell, Peripheral Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Lymphoma, Non-Hodgkin Prednisone Cyclophosphamide Doxorubicin Vincristine Belinostat |
Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors Anti-Inflammatory Agents Glucocorticoids |