Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    lccc 1637
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03264131
Recruitment Status : Recruiting
First Posted : August 28, 2017
Last Update Posted : April 26, 2019
Sponsor:
Collaborator:
Seattle Genetics, Inc.
Information provided by (Responsible Party):
UNC Lineberger Comprehensive Cancer Center

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.


Condition or disease Intervention/treatment Phase
Lymphoma Adult T-Cell Leukemia/Lymphoma Lymphatic Diseases Drug: Brentuximab Vedotin Drug: CHEP Phase 2

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Brentuximab Vedotin With Cyclophosphamide, Doxorubicin, Etoposide, and Prednisone (BV-CHEP) for the Treatment of Adult T-Cell Leukemia/Lymphoma: A Phase II Trial of the Rare Lymphoma Working Group
Actual Study Start Date : October 15, 2018
Estimated Primary Completion Date : January 30, 2021
Estimated Study Completion Date : January 30, 2026


Arm Intervention/treatment
Experimental: Open-label, Multicenter, Single-Arm
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 4 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
Brentuximab Vedotin will be given at 1.8 mg/kg IV over approximately 30 minutes on D1 every 21 days for 4-6 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).

Drug: CHEP

Cyclophosphamide- 750 mg/m^2 IV over approximately 1 hour on D1 every 21 days for 4-6 cycles

Doxorubicin- 50 mg/m^2 IV over approximately 3-5 minutes on D1 every 21 days for 4-6 cycles.

Etoposide - 100 mg/m^2 IV over approximately 1 hour each day for 3 days every 21 days for 4-6 cycles.

Prednisone - 100 mg, orally once daily for 5 days every 21 days for 4-6 cycles.





Primary Outcome Measures :
  1. Proportion of subjects with Complete Response after 4-6 cycles of brentuximab vedotin in combination with cyclophosphamide, doxorubicin, etoposide, and prednisone (BV-CHEP) [ Time Frame: 18 weeks ]
    Criteria for CR after 4-6 cycles of BV-CHEP will be based on the International Workshop to standardize response criteria for malignant lymphomas (i.e. Lugano Criteria).


Secondary Outcome Measures :
  1. Overall response rate (ORR) associated with 4-6 cycles of BV-CHEP therapy in patients with adult T-Cell leukemia/lymphoma. [ Time Frame: 70 weeks ]
    ORR will be evaluated as the rate of complete responses (CR) + partial responses (PR) as defined by the International Workshop to standardize response criteria for malignant lymphomas (i.e. Lugano Criteria). Patients with leukemic component to their disease at baseline will be assessed per Adult T-Cell Leukemia/Lymphoma National Comprehensive Cancer Network (NCCN) guidelines version 2.2017

  2. Progression-free survival (PFS) for BV-CHEP in patients with adult T-cell leukemia/lymphoma who received or did not receive BV maintenance. [ Time Frame: 3 years ]
    PFS will be assessed from day 1 of treatment until disease progression (based on International Workshop to standardize response criteria for malignant lymphomas (i.e. Lugano Criteria).

  3. Duration of response to BV-CHEP in patients with adult T-cell leukemia/lymphoma who received or did not receive BV maintenance. [ Time Frame: 3 years ]
    Duration of response is defined as the time from documentation of tumor response per Lugano criteria to disease progression.

  4. Overall survival (OS) of patients with adult T-cell leukemia/lymphoma treated with BV-CHEP who received or did not receive BV maintenance therapy. [ Time Frame: 3 years ]
    Overall survival is defined as the time from day 1 of treatment until death from any cause.

  5. Toxicity and tolerability of BV-CHEP and BV maintenance therapy via National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE v4) [ Time Frame: 70 weeks ]
    Toxicity and tolerability of therapy will be assessed via the NCI CTCAE v4.03



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

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): NCT03264131


Contacts
Layout table for location contacts
Contact: Bob Broomer 919-966-9257 bob_broomer@med.unc.edu
Contact: Jen Reed 919-445-4211 jen_reed@med.unc.edu

Locations
Layout table for location information
United States, Massachusetts
Boston Medical Center Recruiting
Boston, Massachusetts, United States, 02118
Contact: Mark Sloan, MD    617-638-2367    mark.sloan@bmc.org   
United States, North Carolina
Lineberger Comprehensive Cancer Center at the University of North Carolina at Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27599
Contact: Bob Broomer    919-966-9257    bob_broomer@med.unc.edu   
Sponsors and Collaborators
UNC Lineberger Comprehensive Cancer Center
Seattle Genetics, Inc.
Investigators
Layout table for investigator information
Principal Investigator: Dittus Christopher, DO, MPH UNC Lineberger Comprehensive Cancer Center

Layout table for additonal information
Responsible Party: UNC Lineberger Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT03264131     History of Changes
Other Study ID Numbers: LCCC 1637
First Posted: August 28, 2017    Key Record Dates
Last Update Posted: April 26, 2019
Last Verified: April 2019

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by UNC Lineberger Comprehensive Cancer Center:
Brentuximab Vedotin
Adcetris
Lymphoma
Leukemia
CD30
Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Leukemia
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Lymphatic Diseases
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Leukemia, Lymphoid
Prednisone
Cyclophosphamide
Doxorubicin
Etoposide
Antibodies, Monoclonal
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