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

This is an interventional treatment trial for Lymphoma focused on measuring Brentuximab Vedotin, Adcetris, Lymphoma, Leukemia, CD30 Read More

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria to participate in this study:

1. Informed consent and HIPAA authorization for release of personal health information obtained.
2. Age ≥ 18 years at the time of consent.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2.

4. 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).
5. Documented negative serologic testing for human immunodeficiency virus (HIV).
6. 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.

7. 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

   System: Hepatic - Alanine aminotransferase (ALT)

   Laboratory Value: ≤ 2.5 × ULN

8. 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.
9. 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.
10. 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.
11. As determined by the enrolling physician or protocol designee, willingness and ability of the subject to understand and comply with study procedures
12. Prior Treatment: Previously untreated or has received a maximum of one cycle of any combination chemotherapy (e.g. cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), CHOEP, DA-EPOCH, doxorubicin, cyclophosphamide, cytarabine, vincristine, methotrexate/Etoposide, ifosfamide, cytarabine, methotrexate (CODOX-M/IVAC), HyperCVAD) within 4 weeks of signing the main consent form. Additionally, a patient may have taken antiretroviral therapy (e.g. azidothymidine (AZT) and/or IFN) at any time prior to study enrollment
13. CD30 expression determined by flow cytometry or IHC. NOTE: If CD30 testing was previously done on the biopsy sample from diagnosis, this information will be collected. If CD30 testing was not done, an archival sample from the biopsy used for diagnosis will be requested and tested for CD30. CD30 testing will also be done on the bone marrow tissue collected from the bone marrow exam. If we are unable to obtain an archival sample or if the bone marrow exam is negative, a new biopsy will be performed to confirm the diagnosis and test for CD30.

Exclusion Criteria:

Subjects who meet any of the following criteria should be excluded from study participation:

1. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
2. 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.
3. Previous exposure to brentuximab vedotin (BV).
4. History of allergic response to BV-CHEP or its components or to any of the required prophylactic medications or reasonable alternatives.
5. Symptomatic cardiac disease including ventricular dysfunction, left ventricular ejection fraction < 40%, symptomatic coronary artery disease or symptomatic arrhythmias
6. Subjects with severe hepatic insufficiency Child-Pugh Score > 6
7. Subjects with severe renal impairment (i.e., creatinine clearance ≤ 30 mL/min; see Appendix B - Renal Impairment Guidelines).
8. Exclude patients with pre-existing neuropathy grade 2 or higher.
9. 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).
10. 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.