Brentuximab Vedotin + Rituximab as Frontline Therapy for Pts w/ CD30+ and/or EBV+ Lymphomas
This study is currently recruiting participants.
Verified March 2013 by Northwestern University
Sponsor:
Northwestern University
Collaborator:
Seattle Genetics, Inc.
Information provided by (Responsible Party):
Adam Petrich, Northwestern University
ClinicalTrials.gov Identifier:
NCT01805037
First received: February 27, 2013
Last updated: March 4, 2013
Last verified: March 2013
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Purpose
The purpose of this study is to evaluate how safe and effective the combination of two different drugs (brentuximab vedotin and rituximab) is in patients with certain types of lymphoma. This study is for patients who have a type of lymphoma that expresses a tumor marker called CD30 and/or a type that is associated with the Epstein-Barr virus (EBV-related lymphoma) and who have not yet received any treatment for their cancer, except for dose-reduction or discontinuation (stoppage) of medications used to prevent rejection of transplanted organs (for those patients who have undergone transplantation). This study is investigating the combination of brentuximab vedotin and rituximab as a first treatment for lymphoma patients
| Condition | Intervention | Phase |
|---|---|---|
|
Adult Grade III Lymphomatoid Granulomatosis Adult Nasal Type Extranodal NK/T-cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Contiguous Stage II Adult Burkitt Lymphoma Contiguous Stage II Adult Diffuse Large Cell Lymphoma Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma Contiguous Stage II Adult Lymphoblastic Lymphoma Contiguous Stage II Grade 1 Follicular Lymphoma Contiguous Stage II Grade 2 Follicular Lymphoma Contiguous Stage II Grade 3 Follicular Lymphoma Contiguous Stage II Mantle Cell Lymphoma Contiguous Stage II Marginal Zone Lymphoma Contiguous Stage II Small Lymphocytic Lymphoma Cutaneous B-cell Non-Hodgkin Lymphoma Epstein-Barr Virus Infection Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Hepatosplenic T-cell Lymphoma Intraocular Lymphoma Nodal Marginal Zone B-cell Lymphoma Noncontiguous Stage II Adult Burkitt Lymphoma Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma Noncontiguous Stage II Adult Lymphoblastic Lymphoma Noncontiguous Stage II Grade 1 Follicular Lymphoma Noncontiguous Stage II Grade 2 Follicular Lymphoma Noncontiguous Stage II Grade 3 Follicular Lymphoma Noncontiguous Stage II Mantle Cell Lymphoma Noncontiguous Stage II Marginal Zone Lymphoma Noncontiguous Stage II Small Lymphocytic Lymphoma Noncutaneous Extranodal Lymphoma Peripheral T-cell Lymphoma Post-transplant Lymphoproliferative Disorder Progressive Hairy Cell Leukemia, Initial Treatment Recurrent Adult Burkitt Lymphoma Recurrent Adult Diffuse Mixed Cell Lymphoma Recurrent Adult Diffuse Small Cleaved Cell Lymphoma Recurrent Adult Grade III Lymphomatoid Granulomatosis Recurrent Adult Hodgkin Lymphoma Recurrent Adult Immunoblastic Large Cell Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Adult T-cell Leukemia/Lymphoma Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Mycosis Fungoides/Sezary Syndrome Recurrent Small Lymphocytic Lymphoma Refractory Hairy Cell Leukemia Small Intestine Lymphoma Splenic Marginal Zone Lymphoma Stage I Adult Burkitt Lymphoma Stage I Adult Diffuse Large Cell Lymphoma Stage I Adult Diffuse Mixed Cell Lymphoma Stage I Adult Diffuse Small Cleaved Cell Lymphoma Stage I Adult Hodgkin Lymphoma Stage I Adult Immunoblastic Large Cell Lymphoma Stage I Adult Lymphoblastic Lymphoma Stage I Adult T-cell Leukemia/Lymphoma Stage I Cutaneous T-cell Non-Hodgkin Lymphoma Stage I Grade 1 Follicular Lymphoma Stage I Grade 2 Follicular Lymphoma Stage I Grade 3 Follicular Lymphoma Stage I Mantle Cell Lymphoma Stage I Marginal Zone Lymphoma Stage I Small Lymphocytic Lymphoma Stage IA Mycosis Fungoides/Sezary Syndrome Stage IB Mycosis Fungoides/Sezary Syndrome Stage II Adult Hodgkin Lymphoma Stage II Adult T-cell Leukemia/Lymphoma Stage II Cutaneous T-cell Non-Hodgkin Lymphoma Stage IIA Mycosis Fungoides/Sezary Syndrome Stage IIB Mycosis Fungoides/Sezary Syndrome Stage III Adult Burkitt Lymphoma Stage III Adult Diffuse Large Cell Lymphoma Stage III Adult Diffuse Mixed Cell Lymphoma Stage III Adult Diffuse Small Cleaved Cell Lymphoma Stage III Adult Hodgkin Lymphoma Stage III Adult Immunoblastic Large Cell Lymphoma Stage III Adult Lymphoblastic Lymphoma Stage III Adult T-cell Leukemia/Lymphoma Stage III Cutaneous T-cell Non-Hodgkin Lymphoma Stage III Grade 1 Follicular Lymphoma Stage III Grade 2 Follicular Lymphoma Stage III Grade 3 Follicular Lymphoma Stage III Mantle Cell Lymphoma Stage III Marginal Zone Lymphoma Stage III Small Lymphocytic Lymphoma Stage IIIA Mycosis Fungoides/Sezary Syndrome Stage IIIB Mycosis Fungoides/Sezary Syndrome Stage IV Adult Burkitt Lymphoma Stage IV Adult Diffuse Large Cell Lymphoma Stage IV Adult Diffuse Mixed Cell Lymphoma Stage IV Adult Diffuse Small Cleaved Cell Lymphoma Stage IV Adult Hodgkin Lymphoma Stage IV Adult Immunoblastic Large Cell Lymphoma Stage IV Adult Lymphoblastic Lymphoma Stage IV Adult T-cell Leukemia/Lymphoma Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma Stage IV Grade 1 Follicular Lymphoma Stage IV Grade 2 Follicular Lymphoma Stage IV Grade 3 Follicular Lymphoma Stage IV Mantle Cell Lymphoma Stage IV Marginal Zone Lymphoma Stage IV Small Lymphocytic Lymphoma Stage IVA Mycosis Fungoides/Sezary Syndrome Stage IVB Mycosis Fungoides/Sezary Syndrome T-cell Large Granular Lymphocyte Leukemia Testicular Lymphoma Untreated Hairy Cell Leukemia Waldenström Macroglobulinemia |
Drug: brentuximab vedotin Biological: rituximab Other: laboratory biomarker analysis |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase I-II Trial of Brentuximab Vedotin Plus Rituximab as Frontline Therapy for Patients With CD30+ and/or EBV+ Lymphomas |
Resource links provided by NLM:
Further study details as provided by Northwestern University:
Primary Outcome Measures:
- For Phase I: Determine the Dose Limiting Toxicity (DLT) of brentuximab vedotin and rituximab in combination [ Time Frame: The 1st 21 days ] [ Designated as safety issue: Yes ]The DLT of brentuximab vedotin and rituximab in combination will be assessed at baseline and each week during the first 21 days (1 cycle=21 days).
- Phase I: Determine the Maximum Tolerated Dose (MTD) of brentuximab vedotin and rituximab in combination [ Time Frame: The 1st 21 days ] [ Designated as safety issue: Yes ]The safety of brentuximab vedotin and rituximab in combination will be assessed at baseline and each week during the first 21 days (1 cycle=21 days) which will assist in providing the MTD, also known as the Recommended Phase II Dose, which will be the dose given in Phase II of the trial.
- For Phase II: Efficacy of study treatment will be measured by anti-tumor activity as detected from imaging scans [ Time Frame: Prior to beginning treatment in week 5 ] [ Designated as safety issue: No ]The efficacy, or anti-tumor activity, of brentuximab vedotin and rituximab will be measured at baseline and before receiving treatment in week 5. This will be evaluated by assessing PET or CT imaging scans.
- For Phase II: Efficacy of study treatment will be measured by anti-tumor activity as detected from imaging scans [ Time Frame: Prior to beginning treatment in week 11 ] [ Designated as safety issue: No ]The efficacy, or anti-tumor activity, of brentuximab vedotin and rituximab will be measured before receiving treatment in week 11. This will be evaluated by assessing PET or CT imaging scans.
Secondary Outcome Measures:
- Phase II: Further evaluate toxicity of treatment by evaluating adverse events [ Time Frame: Prior to dosing at week 5 or until disease progression (maximum 1 year) ] [ Designated as safety issue: Yes ]Toxicity, both frequency and severity, will continue to be measured by monitoring the occurence of adverse events. Assessments of toxicity will occur prior to treatment for week 5.
- Phase II: Further evaluate toxicity of treatment by evaluating adverse events [ Time Frame: Prior to dosing at week 11 or until disease progression (maximum 1 year) ] [ Designated as safety issue: Yes ]Toxicity, both frequency and severity, will continue to be measured by monitoring the occurence of adverse events. Assessments of toxicity will occur prior to treatment for week 11.
- Phase II: Further evaluate efficacy of treatment by measuring Progression Free Survival (PFS) [ Time Frame: Time elapsed from start of treatment to date of disease progression (maximum 3 years) ] [ Designated as safety issue: No ]Study treatment efficacy will be evaluated using PET or CT scan images to determine Progression Free Survival which is measured from treatment initiation until tumor progression
- Phase II: Further evaluate efficacy of treatment by measuring Overall Survival (OS) [ Time Frame: Time elapsed from start of treatment to date of disease progression (maximum 3 years) ] [ Designated as safety issue: No ]Efficacy of treatment will be evaluated using PET or CT scan images to determine Overall Survival which is measured as time from treatment initiation until disease progression, patients will be followed up to 3 years.
- Determining the effects of the combination of brentuximab vedotin and rituximab on biomarkers of Epstein-Barr Virus [ Time Frame: At baseline and once per cycle (1 cycle=3 weeks) for the duration of treatment up to 1 year ] [ Designated as safety issue: No ]The effect of study treatment on biomarkers of the Epstein-Barr Virus will be evaluated from blood collected at baseline and once per treatment cycle (every 3 weeks).
- Continued efficacy of treatment evaluation as measured by time between treatment initiation and time of first cytotoxic chemotherapy [ Time Frame: Time from start of study treatment to time of first dose of cytotoxic chemotherapy (maximum of 1 year) ] [ Designated as safety issue: No ]Efficacy of study treatment will also be determined by evaluating the amount of time from start of study treatment to time of first dose of cytotoxic chemotherapy (administered to treat lymphoma).
- Rates of graft rejection as another measurement of efficacy [ Time Frame: Time from 1st dose until end of treatment (maximum 1 year) ] [ Designated as safety issue: No ]Graft rejection during study treatment will be measured to evaluate therapy efficacy.
Other Outcome Measures:
- Correlate response and outcomes relating to treatment with protein expression and Epstein-Barr virus biomarkers and blood levels [ Time Frame: At baseline, once during each 3 week cycle, and after 1 year of treatment ] [ Designated as safety issue: No ]For future studies, tissue samples and blood collected at baseline, once per cycle (3 weeks), and at the conclusion of 1 year of treatment will be used to correlate response and outcomes from therapy with protein expression, biomarkers, and blood levels.
| Estimated Enrollment: | 33 |
| Study Start Date: | March 2013 |
| Estimated Primary Completion Date: | January 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Treatment (brentuximab vedotin, rituximab)
INDUCTION: Patients receive brentuximab vedotin IV over 30 minutes once weekly for 3 weeks and rituximab IV once weekly for 4 weeks. Patients unable to achieve CR may receive additional optional consolidation therapy identical to induction therapy. MAINTENANCE THERAPY: Patients receive brentuximab vedotin IV once every 3 weeks and rituximab IV once every 6 weeks. Treatment repeats every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity. |
Drug: brentuximab vedotin
Given IV
Other Names:
Biological: rituximab
Given IV
Other Names:
Other: laboratory biomarker analysis
Correlative studies
|
Detailed Description:
PRIMARY OBJECTIVES:
I. To evaluate the safety of brentuximab vedotin and rituximab in patients with lymphoid malignancies that are cluster of differentiation (CD) 30 positive (+) and/or Epstein-Barr virus (EBV)+, and to determine the recommended phase 2 dose (RP2D) of the combination. (Phase I) II. To evaluate the efficacy, as measured by response rates, of brentuximab vedotin and rituximab in patients with lymphoid malignancies that are CD30+ and/or EBV+. (Phase II)
SECONDARY OBJECTIVES:
I. To further evaluate the frequency and severity of toxicity. (Phase II) II. To further evaluate the clinical efficacy of the combination of brentuximab vedotin and rituximab, as measured by progression free survival (PFS) and overall survival (OS) at one year after the end of treatment. (Phase II) III. To determine the effects of the combination of brentuximab vedotin and rituximab on markers of EBV activation and proliferation. (Phase II) IV. Further evaluate efficacy as measured by time to cytotoxic chemotherapy. (Phase II) V. Further evaluate efficacy as measured by observed rates of graft rejection. (Phase II)
TERTIARY OBJECTIVES:
I. To determine whether and to what extent CD30 expression predicts for response and outcome.
II. To determine whether and to what extent expression of EBV markers predicts for response and outcome.
III. To determine whether changes in serum levels of EBV correlate with response and subsequent loss of response to therapy.
OUTLINE: This is a phase I, dose-escalation study of brentuximab vedotin followed by a phase II study.
INDUCTION: Patients receive brentuximab vedotin intravenously (IV) over 30 minutes once weekly for 3 weeks and rituximab IV once weekly for 4 weeks. Patients unable to achieve complete remission (CR) may receive additional optional consolidation therapy identical to induction therapy.
MAINTENANCE THERAPY: Patients receive brentuximab vedotin IV once every 3 weeks and rituximab IV once every 6 weeks. Treatment repeats every 21 days for up to 1 year in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 3 months for 1 year, and then every 6 months for 2 years.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Histologically confirmed CD30+ and/or EBV+ lymphoid malignancy; in addition, there must be evidence of CD20 expression (at any level)
- In cases of post-transplant lymphoproliferative disorder (PTLD) arising in patients who are pharmacologically immunosuppressed, reduction of immunosuppression (RI) must be attempted prior to or in conjunction with enrollment, with the exception of those for whom RI would pose excessive threat of clinically significant graft rejection (as judged by local investigator)
- No prior chemotherapy or radiotherapy for PTLD or diffuse large B-cell lymphoma (DLBCL), with the exception of corticosteroids for 10 or fewer days at any dose (no washout period required)
- No prior surgical intervention, unless performed for the sake of tissue diagnosis or on an urgent basis for disease-related threat to life, limb, or organ function
- Bi-dimensionally measurable disease (at least 1 cm)
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Absolute neutrophil count >= 750/mcL
- Platelets >= 50,000/mcl
- Total bilirubin =< 2 X institutional upper limit of normal (ULN)
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum pyruvate glutamate transaminase [SPGT]) =< 3 X institutional ULN
- Creatinine =< 2 X institutional ULN
- NOTE: Patients who do not meet the above criteria because of disease involvement of the organ in question, or because of acute systemic illness due to lymphoma, may enroll with permission of the study Principal Investigator (PI) and approval from the Data Monitoring Committee; this flexibility be allowed due to the heterogeneity of the patient population, the wide range of complications seen in the initial presentation of EBV-related malignancy, and the frequent difficulty encountered in attempting to clearly document that organ dysfunction is the result of an underlying lymphoproliferative disorder
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
- Has not undergone a hysterectomy or bilateral oophorectomy; or
- Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
- Patients must be free of any prior malignancies for >= 1 year; NOTE: the exception to this would be currently treated squamous cell and basal cell carcinoma of the skin, carcinoma in situ of the cervix, breast, or bladder, or surgically removed melanoma in situ of the skin (stage 0) with histologically confirmed free margins of excision; in addition, it is well-recognized that patients at highest risk for EBV-related lymphoma (ie, those with chronic immunosuppression) are also at high risk for various malignancies, both invasive and non-invasive; therefore, exceptions may also be granted on a case-by-case basis, at the discretion of the PI with approval from the Data Monitoring Committee, for those patients with good clinical control of active malignancy, if the EBV-related lymphoma is considered to be a more immediate threat to the subject's health and/or life
- Ability to understand and the willingness to sign a written informed consent; all patients must have signed, witnessed informed consent prior to registration
Exclusion Criteria:
- Chemotherapy (including monoclonal antibodies) or radiotherapy, administered for any condition, within 4 weeks prior to entering the study or incomplete recovery from adverse events due to agents administered more than 4 weeks earlier
- Ongoing treatment with any other investigational agents
- Known central nervous system (CNS) involvement of lymphoma
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to brentuximab vedotin and/or rituximab
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Known human immunodeficiency virus (HIV) infection
- Known John Cunningham (JC) virus infection and/or progressive multifocal leukoencephalopathy (PML)
- Clinically active hepatitis A, B, or C infections; NOTE: patients with chronic hepatitis C (HCV) or hepatitis B (HBV) infection may enroll if other laboratory criteria are met; those with HBV surface antigen positivity may enroll only if maintained on appropriate suppressive antiviral therapy, per treating investigator's discretion, for the duration of enrollment in the trial
- Pregnancy or active nursing of an infant
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01805037
Contacts
| Contact: Study Coordinator | (312)695-1301 | cancertrials@northwestern.edu |
Locations
| United States, Illinois | |
| Northwestern University | Recruiting |
| Chicago, Illinois, United States, 60611 | |
| Contact: Adam M. Petrich, MD 312-695-6180 apetrich@nmff.org | |
| Principal Investigator: Adam M. Petrich, MD | |
| Sub-Investigator: Leo Gordon, MD | |
| Sub-Investigator: Jane Winter, MD | |
| Sub-Investigator: Shuo Ma, MD, PhD | |
| Sub-Investigator: Steven Rosen, MD | |
| Sub-Investigator: Amy Chadburn, MD | |
| University of Chicago | Not yet recruiting |
| Chicago, Illinois, United States, 60637 | |
| Contact: Sonali M. Smith, MD 773-834-2895 smsmith@medicine.bsd.uchicago.edu | |
| Principal Investigator: Sonali M. Smith, MD | |
| United States, Massachusetts | |
| University of Massachusetts Memorial Health Care | Not yet recruiting |
| Worcester, Massachusetts, United States, 01605 | |
| Contact: Andrew M. Evens, MD 508-334-3550 laura.lefko@umassmed.edu | |
| Principal Investigator: Andrew M. Evens, MD | |
Sponsors and Collaborators
Northwestern University
Seattle Genetics, Inc.
Investigators
| Principal Investigator: | Adam Petrich, MD | Northwestern University |
More Information
No publications provided
| Responsible Party: | Adam Petrich, Principal Investigator, Northwestern University |
| ClinicalTrials.gov Identifier: | NCT01805037 History of Changes |
| Other Study ID Numbers: | NU 12H09, NCI-2012-03090, STU00072695 |
| Study First Received: | February 27, 2013 |
| Last Updated: | March 4, 2013 |
| Health Authority: | United States: Institutional Review Board United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Leukemia, Hairy Cell Burkitt Lymphoma Hodgkin Disease Immunoblastic Lymphadenopathy Leukemia Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, T-Cell Leukemia-Lymphoma, Adult T-Cell Lymphoma Lymphoma, Follicular Lymphoma, Non-Hodgkin Lymphomatoid Granulomatosis Lymphoproliferative Disorders Waldenstrom Macroglobulinemia Mycoses |
Mycosis Fungoides Sezary Syndrome Virus Diseases Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Lymphoma, Large-Cell, Immunoblastic Precursor Cell Lymphoblastic Leukemia-Lymphoma Lymphoma, T-Cell Lymphoma, T-Cell, Cutaneous Lymphoma, T-Cell, Peripheral Epstein-Barr Virus Infections Lymphoma, Large-Cell, Anaplastic Lymphoma, B-Cell, Marginal Zone Lymphoma, Extranodal NK-T-Cell Lymphoma, Mantle-Cell |
ClinicalTrials.gov processed this record on May 16, 2013