Adult Lymphocyte Depletion Hodgkin Lymphoma, Adult Lymphocyte Predominant Hodgkin Lymphoma, Adult Mixed Cellularity Hodgkin Lymphoma, Adult Nodular Sclerosis Hodgkin Lymphoma, Stage II Adult Hodgkin Lymphoma, Stage III Adult Hodgkin Lymphoma, Stage IV Adult Hodgkin Lymphoma
Conditions
Brief summary
This phase II trial studies how well giving brentuximab vedotin together with combination chemotherapy works in treating older patients with previously untreated stage II-IV Hodgkin lymphoma (HL). Monoclonal antibody-drug conjugates, such as brentuximab vedotin, can block cancer growth in different ways by targeting certain cells. Drugs used in chemotherapy, such as doxorubicin hydrochloride, vinblastine, and dacarbazine (AVD), work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving brentuximab vedotin, doxorubicin hydrochloride, vinblastine, and dacarbazine together may kill more cancer cells.
Detailed description
LEAD IN: Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for 2 courses in the absence of disease progression or unacceptable toxicity. AVD CHEMOTHERAPY: Patients then receive doxorubicin hydrochloride IV, vinblastine IV, and dacarbazine IV over 30 minutes on days 1 and 15. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients achieving CR receive brentuximab vedotin IV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days.
Interventions
DRUGbrentuximab vedotin
Given IV
DRUGdoxorubicin hydrochloride
Given IV
DRUGvinblastine
Given IV
DRUGdacarbazine
Given IV
PROCEDUREquality-of-life assessment
Ancillary studies
GENETICDNA analysis
Optional correlative studies
GENETICRNA analysis
Optional correlative studies
RADIATIONfludeoxyglucose F 18
Correlative studies
PROCEDUREpositron emission tomography
Correlative studies
OTHERlaboratory biomarker analysis
Optional correlative studies
OTHERimmunohistochemistry staining method
Optional correlative studies
GENETICpolymorphism analysis
Optional correlative studies
Sponsors
Northwestern University
Robert H. Lurie Cancer Center
Seagen Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care * Previously untreated classical Hodgkin lymphoma (i.e., nodular sclerosis, mixed cellularity, lymphocyte depleted, lymphocyte-rich, and not otherwise specified \[NOS\]); nodular lymphocyte predominant Hodgkin lymphoma is not eligible * Stage II, III, and IV disease by Ann Arbor classification * Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 * Patients must have bi-dimensional measurable disease documented in the lymphoma baseline tumor assessment form within 30 days prior to registration (at least 1.5 cm); patients with non-measurable disease in addition to measurable disease must have been assessed within 60 days prior to registration * Patients must have a bone marrow biopsy (bilateral preferred, unilateral acceptable) within 60 days prior to registration * Patients must have a multi gated acquisition scan (MUGA) or echocardiogram within 60 days prior to study registration and the ejection fraction must be \>= 45% * Absolute neutrophil count (ANC) \> 1000/mm\^3 * Platelet count \> 75,000/mm\^3 * Creatinine \< 2.5 mg/dl * Bilirubin \< 3.0 mg/dl * Patients with documented marrow involvement by lymphoma at the time of registration are not required to meet the above hematologic parameters * Patients must not have received prior chemotherapy or radiation therapy for the treatment of Hodgkin lymphoma * Both females and males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug * Patients must sign the informed consent form before registration
Exclusion criteria
* Previous treatment with brentuximab vedotin or any other prior anti-CD30-based antibody therapy * History of another primary malignancy that has not been in remission for at least 3 years; (the following are exempt from the 3-year limit: early stage \[stage I or II\] breast cancer treated with surgery and radiation +/- hormones \[without adjuvant chemotherapy\], non-melanoma skin cancer, fully excised melanoma in situ \[stage 0\], curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Papanicolaou test \[PAP smear\]) * Known cerebral/meningeal disease * Any active systemic viral, bacterial, or fungal infection requiring treatment with antimicrobial therapy within 1 week prior to first dose * Patients with hepatitis B surface antigen (HBsAg) positive hepatitis B virus (HBV) infection; patients with prior history of hepatitis B infection, but immune, with only Immunoglobulin G (IgG) hepatitis core antibody + (HBcAb +) must receive anti-viral prophylaxis (e.g., lamivudine 100mg orally \[po\] daily) for at least 1 week prior to cycle 1 and throughout induction and continuation therapy and for at least 6 months after the last brentuximab vedotin dose; in addition, consultation with a hepatologist is recommended * Patients with a known hypersensitivity to any excipient contained in the drug formulation * Patients with dementia or an altered mental state that would preclude the understanding and rendering of informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Remission Rate After Chemotherapy | after completion of AVD chemotherapy and prior to SGN-35 consolidation, approximately 9 months | The primary objective of this study is to evaluate the complete remission rate among older patients with HL receiving sequential brentuximab vedotin therapy with AVD chemotherapy |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate After 2 Cycles of SGN-35 | 2 cycles of SGN-35 lead-in therapy, approximately 42 days | The incidence of overall response rate to induction SGN-35 will be reported for the initial 22 patients where PET is being employed. |
| Complete Remission Rate Following 2 Cycles of SGN-35 | 2 cycles of lead-in SGN-35, approximately 42 days | The incidence of CR rate to induction SGN-35 will be reported for the initial 22 patients where PET is being employed |
| Safety of Sequential SGN-35/AVD/SGN-35 Therapy | From time of treatment to 30 days after discontinuation of study treatment | Detailed examination of Averse Events, laboratory test results, vital signs or other physical findings. Below we have summarized the top 10 most common Grade 3 and Grade 4 related adverse events. Please see the Adverse Events section of this record for a full listing of Adverse Events. |
| 2-year Progression Free Survival | 2 years from time of registration to study | Progression Free Survival (PFS) is defined as lymphoma progression or death from any cause. This outcome measure is the percentage of patients that have not progressed at 2 years from time of registration. |
| Overall Survival Following SGN-35/AVD Sequential Therapy | up to 2 years from the time of registration | Defined as the percentage of patients that are alive 2 years after registration. |
| 2 Year Event-Free Survival | From registration until treatment failure, up to 2 years | An event is defined as treatment failure including discontinuation of treatment for any reason, such as disease progression, toxicity, patient preference, initiation of new treatment without documented progression, or death. This outcome measure is reported as the percentage of patient that did not have an event at 2 years from registration. |
| Freedom From Progression | from baseline to end of study, approximately 4 years | Measured from the time of study entry to progression of disease. Other causes of treatment failure are not include in freedom from progression. |
| Patient Reported Outcomes for Symptoms and Quality of Life | Baseline and AVD Cycle 1, a total of 6 weeks | Evaluate patient reported outcomes at baseline and during treatment to determine potential symptom palliation, treatment-related symptoms, and overall health-related quality of life. The Function Assessment of Cancer Therapy for Lymphoma (FACT-Lym) scale has a range of 0(minimum score) to 168 (maximum score). Higher scores indicate a better outcome. The mean scores for each timepoint are reported below. |
| Association Between Cumulative Illness Rating Scale (CIRS) With Outcomes | approximately 2 years from treatment start | Number of co-morbidities collected for each patient at baseline and at the end of completion of all therapy utilizing the Cumulative Illness Rating Scare (CIRS). For binary outcomes such as CR, logistic regression will be used to assess the relationship with CIRS score; for time-to-event outcomes, the method of Kalan Meier and the log rank test will be used. The minimum score of the CIRS is 0 and the maximum score is 56. High Scores on the CIRS scale indicate that the patient has more severe comorbidities |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORLeo Gordon, MD
Northwestern University
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized 60-70 years | 25 Participants |
| Age, Customized 71-80 years | 15 Participants |
| Age, Customized >80 years | 8 Participants |
| Albumin less than 4.0 g/dL No | 26 Participants |
| Albumin less than 4.0 g/dL Yes | 22 Participants |
| Bone Marrow Involvement No | 37 Participants |
| Bone Marrow Involvement Yes | 11 Participants |
| Bulky Disease (greater than or equal to 10 cm) No | 43 Participants |
| Bulky Disease (greater than or equal to 10 cm) Yes | 5 Participants |
| ECOG Performance Score 0 | 19 Participants |
| ECOG Performance Score 1 | 20 Participants |
| ECOG Performance Score 2 | 9 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 43 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Histology Classic, not otherwise specified | 12 Participants |
| Histology Lymphocyte Rich | 2 Participants |
| Histology Mixed Cellularity | 12 Participants |
| Histology Nodular Sclerosis | 22 Participants |
| Hodgkin's Lymphoma Stage II | 9 Participants |
| Hodgkin's Lymphoma Stage III | 18 Participants |
| Hodgkin's Lymphoma Stage IV | 21 Participants |
| International Prognostic Score 0-2 | 20 Participants |
| International Prognostic Score 3-7 | 28 Participants |
| Presence of B symptoms? No | 30 Participants |
| Presence of B symptoms? Yes | 18 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants |
| Race (NIH/OMB) White | 44 Participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 5 / 48 |
| other Total, other adverse events | 46 / 48 |
| serious Total, serious adverse events | 20 / 48 |
Outcome results
None listed