Brentuximab Vedotin and Combination Chemotherapy in Treating Patients with Adult T-Cell Leukemia / Lymphoma
- Informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information obtained
- 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 HTLV-1 antibody testing with confirmatory testing via western blot, enzyme-linked immunosorbent assay (ELISA), or molecular testing (polymerase chain reaction [PCR])
- Documented negative serologic testing for human immunodeficiency virus (HIV)
- If positive for hepatitis B virus (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
- Calculated creatinine clearance >= 30 mL/min using the Cockcroft-Gault formula for subjects with creatinine levels > 2.0 x institutional ULN (obtained within three days prior to study treatment)
- Bilirubin =< 3.0 mg/dL (obtained within three days prior to study treatment)
- Aspartate aminotransferase (AST) =< 2.5 x ULN (obtained within three days prior to study treatment)
- Alanine aminotransferase (ALT) =< 2.5 x ULN (obtained within three days prior to study treatment)
- Females of childbearing potential must have a negative serum pregnancy test within three days (72 hours) prior to initiating study treatment; NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
- Females of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 24 weeks (6 months) after treatment discontinuation; the two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method or an intrauterine device that meets < 1% failure rate for protection from pregnancy in the product label
- Male patients with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 24 weeks (6 months) after the last dose of study therapy
- As determined by the enrolling physician or protocol designee, willingness and ability of the subject to understand and comply with study procedures
- Prior treatment: Previously untreated or has received a maximum of one cycle of any combination chemotherapy (e.g. cyclophosphamide/hydroxydaunorubicin/oncovin/prednisone [CHOP], cyclophosphamide/hydroxydaunorubicin/oncovin/etoposide/prednisone, [CHOEP], dose-adjusted etoposide/vincristine/doxorubicin/cyclophosphamide/prednisone [DA-EPOCH], cyclophosphamide/oncovin/doxorubicin/methotrexate-ifosfamide/VePesid/AraC [CODOX-M/IVAC], hyper cyclophosphamide/dexamethasone/doxorubicin/vincristine [CVAD]) within 4 weeks of study entry; additionally, a patient may have taken antiretroviral therapy (e.g. zidovudine [AZT] and/or interferon [IFN]) at any time prior to study enrollment
- 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)
- Exclude patients with pre-existing neuropathy grade 2 or higher
- Patients receiving prohibited medications; prohibited medications or those to be used with caution (i.e., ketoconazole, itraconazole, ritonavir, macrolide antibiotics, erythromycin phenytoin, phenobarbital, carbamazapine, and valproic acid)
- Patients with a parenchymal brain lesion thought to be consistent with active lymphoma on screening computed tomography/magnetic resonance imaging (CT/MRI); of note, patients with cerebral spinal fluid (CSF) involvement alone are not excluded
I. To define the proportion of subjects with complete response (CR) after 4-6 cycles of brentuximab vedotin in combination with cyclophosphamide, doxorubicin hydrochloride (doxorubicin), etoposide phosphate (etoposide), and prednisone (BV-CHEP) in the treatment of adult T-cell leukemia/lymphoma.
I. To estimate the overall response rate (ORR) associated with 4-6 cycles of BV- CHEP therapy in patients with adult T-cell leukemia/lymphoma.
II. To determine progression-free survival (PFS) for BV-CHEP in patients with adult T-cell leukemia/lymphoma who received or did not receive BV maintenance.
III. To determine duration of response to BV-CHEP in patients with adult T-cell leukemia/lymphoma who received or did not receive BV maintenance.
IV. To determine overall survival (OS) of patients with adult T-cell leukemia/lymphoma treated with BV-CHEP who received or did not receive BV maintenance therapy.
V. To evaluate the toxicity and tolerability of BV-CHEP and BV maintenance therapy via the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.03).
I. CD30 expression by immunohistochemistry (IHC).
II. Creation of adult T-cell leukemia/lymphoma (ATLL) xenografts using peripheral blood samples to develop preclinical ATLL models.
Patients receive brentuximab vedotin intravenously (IV) over 30 minutes, cyclophosphamide IV over 1 hour, and doxorubicin hydrochloride IV over 3-5 minutes on day 1, etoposide phosphate IV over 1 hour on days 1-3, and prednisone orally (PO) once daily (QD) on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients with a CR, partial response (PR), or stable disease (SD), CD30 positive disease, and are not eligible for bone marrow transplantation (BMT) (after courses 4 or 6) then proceed to Maintenance Therapy.
MAINTENANCE THERAPY: Patients receive brentuximab vedotin IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 5 years.
Trial Phase Phase II
Trial Type Treatment
UNC Lineberger Comprehensive Cancer Center
Christopher Edward Dittus
- Primary ID LCCC1637
- Secondary IDs NCI-2017-01602
- Clinicaltrials.gov ID NCT03264131