BV-CHEP Chemotherapy for Adult T-cell Leukemia or Lymphoma

NCT03264131 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: LCCC1637
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 4

Brief Summary

Adult T-cell leukemia/lymphoma (ATLL) is a rare form of cancer found mostly among people from the Caribbean islands, Western Africa, Brazil, Iran, and Japan. Most cases of this disease in the United States occur along the East Coast due to emigration from the Caribbean islands. There is currently no standard treatment for ATLL. Research shows that patients who go into first time remission (respond completely or partially to treatment) and have a bone marrow transplant have the best outcomes. Traditional chemotherapy treatments have generally not worked well in patients with ATLL. Additionally, not all patients will be eligible for a bone marrow transplant. The purpose of this study is to see how well individuals with ATLL respond to an investigational cancer treatment. This investigational treatment combines a drug called brentuximab vedotin with a standard chemotherapy treatment made up of cyclophosphamide, doxorubicin, etoposide, and prednisone. This treatment is considered investigational because it is not approved by the United States Food and Drug Administration (FDA) for the treatment of ATLL. Brentuximab vedotin, also known as Adcetris, is approved by the United States Food and Drug Administration (FDA) for treatment of certain types of lymphomas, including peripheral T-cell lymphomas when combined with cyclophosphamide, doxorubicin, and prednisone in patients whose cancer cells express a type of marker called CD30. Brentuximab vedotin is an antibody that also has a chemotherapy drug attached to it. Antibodies are proteins that are part of the immune system. They can stick to and attack specific targets on cancer cells. The antibody part of brentuximab vedotin sticks to a target called cluster of differentiation 30 (CD30) that is located on the outside of the cancer cells. Normal cells have little or no CD30 on their surface. ATLL cancer cells often have a larger amount of CD30 on their surface than normal cells. However, CD30 is found in different amounts on ATLL cancer cells. This study will also test the amount of CD30 found on each participant's cancer cells. Researchers will be looking to see if the response to the study treatment varies based on the amount of CD30 found on the outside participants' cancer cells. In another study, brentuximab vedotin was combined in another study with cyclophosphamide, doxorubicin, and prednisone. The study included patients with various types of T-cell lymphomas. Two of the patients enrolled in that study had ATLL. Both had a complete response (no evidence of disease). The researchers in this study (LCCC 1637) have added etoposide to the combination of brentuximab vedotin with cyclophosphamide, doxorubicin, and prednisone. They predict that the addition of etoposide will improve patient outcomes. Research shows that etoposide helps improve outcomes in patients with certain types of T-cell lymphomas who undergo chemotherapy treatment. This investigational combination of brentuximab vedotin with cyclophosphamide, doxorubicin, etoposide, and prednisone is called BV-CHEP.

Conditions

Lymphoma; Adult T-Cell Leukemia/Lymphoma; Lymphatic Diseases

Keywords

Brentuximab Vedotin; Adcetris; Lymphoma; Leukemia; CD30

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate After 2-6 Cycles of Brentuximab Vedotin in Combination With Cyclophosphamide, Doxorubicin, Etoposide, and Prednisone (BV-CHEP)

  The response was assessed based on the International Workshop to standardize response criteria for malignant lymphomas (i.e., Lugano Criteria per Cheson, et al. J Clin Oncol. 2014;32(27):3059-68; Complete Response: Positron emission tomography (PET): Complete metabolic response Computerized tomography (CT): Target must regress to ≤ 1.5 cm in the largest transverse diameter (LDi) or no extra lymphatic sites of disease. Partial Response: PET: reduced uptake compared with baseline, and CT: ≥50% decrease in the sum of the products of diameters (SPD).No Response or Stable Disease: No metabolic response on PET or \< 50% decrease from baseline in SPD of up to 6 dominant, measurable nodes and extra nodal sites on CT. Progressive Disease: PET: Score 4 or 5 with an increase in the intensity of uptake or CT: an individual node/lesion must be abnormal with LDi \> 1.5 cm, increase by ≥ 50% from the cross product of the LDi and shortest axis perpendicular to LDi (SDi).

  18 weeks

Secondary Outcomes (5)

• Overall Response Rate (ORR) Associated With 2-6 Cycles of BV-CHEP Therapy in Patients With Adult T-Cell Leukemia/Lymphoma.

  70 weeks

• Progression-free Survival (PFS) for BV-CHEP in Patients With Adult T-cell Leukemia/Lymphoma Who Received or Did Not Receive BV Maintenance.

  5 years

• Duration of Response to BV-CHEP in Patients With Adult T-cell Leukemia/Lymphoma Who Received or Did Not Receive BV Maintenance.

  3 years

• Overall Survival (OS) of Patients With Adult T-cell Leukemia/Lymphoma Treated With BV-CHEP Who Received or Did Not Receive BV Maintenance Therapy.

  5 years

• Toxicity and Tolerability of BV-CHEP and BV Maintenance Therapy Via National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4)

  70 weeks

Study Arms (1)

Open-label, Multicenter, Single-Arm

EXPERIMENTAL

This is a single-arm intervention where patients will receive concurrent therapy with BV+CHEP \[(brentuximab vedotin; 1.8 mg/kg IV, on D1 every 21 days) (cyclophosphamide 750 mg/m\^2 on D1; doxorubicin 50 mg/m\^2 on D1, etoposide 100 mg/m\^2 IV infusion on D1-3; prednisone 100 mg orally once daily on D1-5; cycle length every 21 days)\] for 2 to 6 cycles of induction therapy. After 6 cycles of BV + CHEP, responders (CR, PR or SD) who are not eligible for BMT and have CD30-positive ATLL will continue maintenance therapy with BV alone (1.8 mg/kg IV, every 21 days) until disease progression, withdrawal due to toxicity or death.

Drug: Brentuximab Vedotin; Drug: CHEP

Interventions

Brentuximab Vedotin DRUG

Brentuximab Vedotin will be given at 1.8 mg/kg IV over approximately 30 minutes on D1 every 21 days for 2-6 cycles. Responders (CR, PR or SD) who are not eligible for bone marrow transplant (BMT) and have CD30-positive ATLL will continue maintenance therapy with BV alone (1.8 mg/kg IV for approximately 30 minutes, every 21 days).

Open-label, Multicenter, Single-Arm

CHEP DRUG

Cyclophosphamide- 750 mg/m\^2 IV over approximately 1 hour on D1 every 21 days for 2-6 cycles Doxorubicin- 50 mg/m\^2 IV over approximately 3-5 minutes on D1 every 21 days for 2-6 cycles. Etoposide - 100 mg/m\^2 IV over approximately 1 hour each day for 3 days every 21 days for 2-6 cycles. Prednisone - 100 mg, orally once daily for 5 days every 21 days for 2-6 cycles.

Open-label, Multicenter, Single-Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent and HIPAA authorization for release of personal health information obtained.
• Age ≥ 18 years at the time of consent.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.
• Histological confirmation of biopsy-proven peripheral T-cell leukemia/lymphoma consistent with ATLL
• Included subtypes will be: acute, lymphomatous, and chronic unfavorable. Chronic unfavorable is defined as the chronic variant with at least one of the following: lactate dehydrogenase (LDH)\>upper limit of normal (ULN), blood urea nitrogen (BUN)\>ULN, Albumin\<lower limit of normal (LLN)
• Positive human T-lymphotropic virus-1 (HTLV-1) antibody testing with confirmatory testing via Western blot, enzyme-linked immunosorbent assay (ELISA), or molecular testing (PCR).
• Documented negative serologic testing for human immunodeficiency virus (HIV).
• If positive for HBV exposure or prior infection, can continue to participate in trial with prophylactic entecavir (for HBV). If positive for hepatitis c virus (HCV) exposure or active infection, can participate in trial with monitoring for liver function abnormalities.
• Demonstrate adequate organ function as defined below; all screening labs to be obtained within three days prior to study treatment.
• System: Renal -Calculated creatinine clearance
• Laboratory Value: ≥ 30 mL/min using the Cockcroft-Gault formula for subjects with creatinine levels \> 2.0 x institutional ULN
• System: Hepatic - Bilirubin
• Laboratory Value: ≤ 3.0 mg/dL
• System: Hepatic - Aspartate aminotransferase (AST)
• Laboratory Value: ≤ 2.5 × ULN

You may not qualify if:

• Subjects who meet any of the following criteria should be excluded from study participation:
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• Has a known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least five years.
• Previous exposure to brentuximab vedotin (BV).
• History of allergic response to BV-CHEP or its components or to any of the required prophylactic medications or reasonable alternatives.
• Symptomatic cardiac disease including ventricular dysfunction, left ventricular ejection fraction \< 40%, symptomatic coronary artery disease or symptomatic arrhythmias
• Subjects with severe hepatic insufficiency Child-Pugh Score \> 6
• Subjects with severe renal impairment (i.e., creatinine clearance ≤ 30 mL/min; see Appendix B - Renal Impairment Guidelines).
• Exclude patients with pre-existing neuropathy grade 2 or higher.
• Patients receiving prohibited medications listed in the patient handout provided in 11.4 Appendix D: Prohibited Medications or Those to be used with Caution (ie, ketoconazole, itraconazole, ritonavir, macrolide antibiotics, erythromycin phenytoin, phenobarbital, carbamazepine, and valproic acid).
• Patients with a parenchymal brain lesion thought to be consistent with active lymphoma on screening CT/MRI. Of note, patients with cerebrospinal fluid (CSF) involvement alone are not excluded.

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Seagen Inc.: collaborator

Study Sites (4)

South Broward/Memorial Healthcare System

Hollywood, Florida, 33021, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Beth Israel Deaconess Medical Center (BIDMC)

Boston, Massachusetts, 02215, United States

Location

Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Related Links

• University of North Carolina Lineberger Comprehensive Cancer Center Clinical Trials

MeSH Terms

Conditions

Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Lymphatic Diseases; Leukemia

Interventions

Brentuximab Vedotin

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Hematologic Diseases

Intervention Hierarchy (Ancestors)

Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Melahat Garipagaoglu Canter
• Organization: UNC Lineberger Comprehensive Cancer Center

Melahat_Canter@med.unc.edu

919-962-0000

Study Officials

• Dittus Christopher, DO, MPH

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 15, 2017
• First Posted: August 28, 2017
• Study Start: October 11, 2018
• Primary Completion: December 15, 2023
• Study Completion (Estimated): December 15, 2028
• Last Updated: February 10, 2025
• Results First Posted: February 10, 2025

Record last verified: 2025-01

Locations

US (4)