Recurrent Hodgkin Lymphoma, Refractory Hodgkin Lymphoma
Conditions
Brief summary
This phase II trial studies how well brentuximab vedotin before autologous (taken from an individual's own cells) stem cell transplant works in treating patients with Hodgkin lymphoma. Monoclonal antibody-drug conjugates, such as brentuximab vedotin, can block cancer growth in different ways by targeting certain cells.
Detailed description
PRIMARY OBJECTIVES: I. The primary objective of this study is to determine the activity of salvage brentuximab vedotin in Hodgkin lymphoma prior to autologous hematopoietic stem cell transplantation, as measured by overall response rate (ORR). SECONDARY OBJECTIVES: I. To describe the safety, toxicity, and tolerability of brentuximab vedotin as a salvage regimen. II. To summarize the stem cell mobilization results of patients receiving brentuximab vedotin as salvage therapy (e.g., total cluster of differentiation (CD)34+ cell yield, number of apheresis days, proportion of patients who achieve \>= 3 x 10\^6 CD34+ cells/kg). III. To evaluate potential changes in Hodgkin lymphoma biological markers of patients treated with brentuximab vedotin as first line salvage therapy. IV. To examine and characterize the outcomes of patients who receive brentuximab vedotin as first line salvage followed by autologous hematopoietic stem cell transplantation (AHCT) (e.g., toxicity, 2-year progression free survival \[PFS\], overall survival \[OS\], relapse-progression incidence and non-relapse mortality rate \[NRM\]) OUTLINE: Patients receive brentuximab vedotin intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 courses. Patients in the new cohort receive regular study dose of brentuximab vedotin for courses 1 and 2. Patients not achieving complete remission (CR) after 2 courses receive higher-dose brentuximab vedotin IV over 60 minutes on day 1 for 2 additional courses. After completion of study treatment, patients are followed up at 21 days.
Interventions
DRUGbrentuximab vedotin
Given IV
Sponsors
National Cancer Institute (NCI)
City of Hope Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
11 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients must have histologically documented or cytologically confirmed Hodgkin lymphoma with CD 30 expression * Patients must have absolute neutrophil count (ANC) \>= 1000/uL; neupogen (filgrastim) can be given prior to start of SGN-35 (brentuximab vedotin) and during SGN-35 treatment to achieve target ANC \>= 1000/uL * Patients must have platelets (Plts) \>= 50,000/uL; platelet transfusion can be given prior to the start of SGN-35 and during SGN-35 treatment to achieve a target plt \>= 50,000/uL * Patients must have measurable disease \> 1.5 cm evidenced by computed tomography (CT) scan of the neck/chest/abdomen(abd)/pelvis or CT/positron emission tomography (PET) scans * Patient must be either primary refractory to one frontline induction therapy or relapsed after one frontline induction therapy; patients who do not achieve complete remission after induction therapy are also eligible * Patients cannot have had a second line salvage treatment (chemotherapy, biologic agents, investigational drugs, or radiation) or have had an autologous or allogeneic hematopoietic stem cell transplantation; patients can have had mixed frontline therapy such as 2-4 cycles of ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) followed by 2-4 cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) as long as the induction chemotherapy is not more than 8 cycles in total length * Radiation use as part of induction regimen or consolidation (within 90 days after completion of induction chemotherapy) is allowed * 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 * Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study * Male subject agrees to use an acceptable method of contraception for the duration of the study * Life expectancy of greater than 3 months * Karnofsky performance status of \> 60% * ANC \>= 1000/uL * Plts \>= 50,000/uL * Total bilirubin within 1.5 x of the upper limit of normal (ULN) institutional limits, patients with elevation of unconjugated bilirubin alone, as in Gilbert's disease, are eligible * Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \< 2.5 X institutional ULN (unless demonstrated Hodgkin lymphoma involvement of the liver) * Calculated creatinine clearance \>30 ml/min (unless demonstrated Hodgkin lymphoma involvement of the kidney) ELIGIBILITY FOR 2.4 MG/KG DOSING IN THE NEW COHORT: \- In addition to the inclusion/
Exclusion criteria
outlined, to be eligible for treatment with the higher 2.4 mg/kg dose of brentuximab vedotin in the new cohort of 20 additional patients, best response after 2 cycles of brentuximab vedotin administered at the 1.8 mg/kg dose, must be partial remission (PR) or stable disease (SD) as determined by radiographic imaging
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate Among Patients With Salvage Brentuximab Vedotin (BV) | 21 days after completion of last course of study treatment, up to 5 years | The overall response rate is calculated as the percent of evaluable patients that have confirmed CR or PR by radiographic imaging, and the exact 95% confidence interval is calculated for this estimate. Per Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007) for target lesions and assessed by CT/PET scans: Complete Response (CR), complete disappearance of all detectable clinical and radiographic evidence of disease; Partial Response (PR), ≥50% decrease in the sum of the product of the diameters of up to six of the largest dominant nodes or nodal masses. |
| Complete Response (CR) Rate Among Patients With Salvage Brentuximab Vedotin (BV) | 21 days after completion of last course of study treatment, up to 5 years | The CR rate is calculated as the percent of evaluable patients that have confirmed CR by radiographic imaging, and the exact 95% confidence interval is calculated for this estimate. Per Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007) for target lesions and assessed by CT/PET scans: Complete Response (CR), complete disappearance of all detectable clinical and radiographic evidence of disease. |
| Overall Response Rate in Cohort #2 | 21 days after completion of last course of study treatment, up to 5 years | The overall response rate is calculated as the percent of evaluable patients that have confirmed CR or PR by radiographic imaging, and the exact 95% confidence interval is calculated for this estimate. Per Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007) for target lesions and assessed by CT/PET scans: Complete Response (CR), complete disappearance of all detectable clinical and radiographic evidence of disease; Partial Response (PR), ≥50% decrease in the sum of the product of the diameters of up to six of the largest dominant nodes or nodal masses. |
| Complete Response (CR) Rate in Cohort #2 | 21 days after completion of last course of study treatment, up to 5 years | The CR rate is calculated as the percent of evaluable patients that have confirmed CR by radiographic imaging, and the exact 95% confidence interval is calculated for this estimate. Per Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007) for target lesions and assessed by CT/PET scans: Complete Response (CR), complete disappearance of all detectable clinical and radiographic evidence of disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival at Year Two Among AutoHCT Patients With BV | Assessed for up to 5 years, at least half of the surviving participants followed 2+ years | Progression Free Survival (PFS) defined as the time from first treatment day (post AHCT) until objective or symptomatic relapse or death as a result of lymphoma or acute toxicity of treatment. Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formula. |
| Overall Survival at Year Two Among AutoHCT Patients With BV | Assessed for up to 5 years, at least half of the surviving participants followed 2+ years | Overall Survival (OS) defined as the time from first treatment day (post AHCT) until death. Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formula. |
| Total CD34+ Cell Dose Among Patients Receiving Brentuximab Vedotin Followed by Autologous Hematopoietic Stem Cell Transplantation | 60 days after completion of last course of study treatment, up to conditioning regimens | Among the patients receiving salvage Brentuximab Vedotin (BV) followed by Autologous Hematopoietic Stem Cell Transplantation (AutoHCT), their total CD34+ cell yield by stem cell mobilization. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Patients receive salvage brentuximab vedotin IV. | 57 |
| Total | 57 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 32 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 38 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 10 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 | 6 Participants |
| Race (NIH/OMB) White | 36 Participants |
| Region of Enrollment United States | 57 Participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 6 / 37 | 2 / 20 |
| other Total, other adverse events | 37 / 37 | 20 / 20 |
| serious Total, serious adverse events | 4 / 37 | 0 / 20 |
Outcome results
Primary
Complete Response (CR) Rate Among Patients With Salvage Brentuximab Vedotin (BV)
The CR rate is calculated as the percent of evaluable patients that have confirmed CR by radiographic imaging, and the exact 95% confidence interval is calculated for this estimate. Per Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007) for target lesions and assessed by CT/PET scans: Complete Response (CR), complete disappearance of all detectable clinical and radiographic evidence of disease.
Time frame: 21 days after completion of last course of study treatment, up to 5 years
Population: Among the 57 enrolled patients, only 56 patients were evaluable for efficacy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients Receive Brentuximab Vedotin | Complete Response (CR) Rate Among Patients With Salvage Brentuximab Vedotin (BV) | 42.9 percentage of participants with response |
Primary
Complete Response (CR) Rate in Cohort #2
The CR rate is calculated as the percent of evaluable patients that have confirmed CR by radiographic imaging, and the exact 95% confidence interval is calculated for this estimate. Per Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007) for target lesions and assessed by CT/PET scans: Complete Response (CR), complete disappearance of all detectable clinical and radiographic evidence of disease.
Time frame: 21 days after completion of last course of study treatment, up to 5 years
Population: Among the 20 enrolled patients in Cohort #2, all the 20 patients were evaluable for efficacy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients Receive Brentuximab Vedotin | Complete Response (CR) Rate in Cohort #2 | 55.0 percentage of participants with response |
Primary
Overall Response Rate Among Patients With Salvage Brentuximab Vedotin (BV)
The overall response rate is calculated as the percent of evaluable patients that have confirmed CR or PR by radiographic imaging, and the exact 95% confidence interval is calculated for this estimate. Per Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007) for target lesions and assessed by CT/PET scans: Complete Response (CR), complete disappearance of all detectable clinical and radiographic evidence of disease; Partial Response (PR), ≥50% decrease in the sum of the product of the diameters of up to six of the largest dominant nodes or nodal masses.
Time frame: 21 days after completion of last course of study treatment, up to 5 years
Population: Among the 57 enrolled patients, only 56 patients were evaluable for efficacy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients Receive Brentuximab Vedotin | Overall Response Rate Among Patients With Salvage Brentuximab Vedotin (BV) | 75.0 percentage of participants with response |
Primary
Overall Response Rate in Cohort #2
The overall response rate is calculated as the percent of evaluable patients that have confirmed CR or PR by radiographic imaging, and the exact 95% confidence interval is calculated for this estimate. Per Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007) for target lesions and assessed by CT/PET scans: Complete Response (CR), complete disappearance of all detectable clinical and radiographic evidence of disease; Partial Response (PR), ≥50% decrease in the sum of the product of the diameters of up to six of the largest dominant nodes or nodal masses.
Time frame: 21 days after completion of last course of study treatment, up to 5 years
Population: Among the 20 enrolled patients in Cohort #2, all the 20 patients were evaluable for efficacy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients Receive Brentuximab Vedotin | Overall Response Rate in Cohort #2 | 85.0 percentage of participants with response |
Secondary
Overall Survival at Year Two Among AutoHCT Patients With BV
Overall Survival (OS) defined as the time from first treatment day (post AHCT) until death. Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formula.
Time frame: Assessed for up to 5 years, at least half of the surviving participants followed 2+ years
Population: Among the 57 patients receiving BV, only 50 patients had undergone autologous transplants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients Receive Brentuximab Vedotin | Overall Survival at Year Two Among AutoHCT Patients With BV | 0.93 survival probability |
Secondary
Progression Free Survival at Year Two Among AutoHCT Patients With BV
Progression Free Survival (PFS) defined as the time from first treatment day (post AHCT) until objective or symptomatic relapse or death as a result of lymphoma or acute toxicity of treatment. Assessed by Kaplan-Meier survival analysis and 95% confidence intervals will be calculated using Greenwood's formula.
Time frame: Assessed for up to 5 years, at least half of the surviving participants followed 2+ years
Population: Among the 57 patients receiving BV, only 50 patients had undergone autologous transplants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Patients Receive Brentuximab Vedotin | Progression Free Survival at Year Two Among AutoHCT Patients With BV | 0.67 survival probability |
Secondary
Total CD34+ Cell Dose Among Patients Receiving Brentuximab Vedotin Followed by Autologous Hematopoietic Stem Cell Transplantation
Among the patients receiving salvage Brentuximab Vedotin (BV) followed by Autologous Hematopoietic Stem Cell Transplantation (AutoHCT), their total CD34+ cell yield by stem cell mobilization.
Time frame: 60 days after completion of last course of study treatment, up to conditioning regimens
Population: Among the 57 enrolled patients, 50 patients receive BV followed by AutoHCT, 32 in Cohort #1 and 18 in Cohort #2.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Patients Receive Brentuximab Vedotin | Total CD34+ Cell Dose Among Patients Receiving Brentuximab Vedotin Followed by Autologous Hematopoietic Stem Cell Transplantation | 6.0 x10^6 cells/kg |
| Cohort #2 | Total CD34+ Cell Dose Among Patients Receiving Brentuximab Vedotin Followed by Autologous Hematopoietic Stem Cell Transplantation | 8.0 x10^6 cells/kg |