Anaplastic Large Cell Lymphoma, Hodgkin Lymphoma
Conditions
Keywords
Hodgkin Lymphoma, Hodgkin Disease, Hodgkin's Disease, Anaplastic Large Cell Lymphoma, ALCL, SGN+Benda, Bendamustine, Brentuximab Vedotin
Brief summary
This is a phase 1/2 multicenter study to assess the safety and effectiveness of brentuximab vedotin and bendamustine, when given together, in patients with Hodgkin Lymphoma or Anaplastic Large Cell Lymphoma (ALCL) that has either returned or did not respond to initial treatment(s). Patients will be accrued at Columbia University Medical Center (CUMC) and at two subsites in Canada.
Detailed description
Brentuximab vedotin will be administered as an outpatient IV infusion on day 1 of each 21-day cycle. Bendamustine will be given as an outpatient infusion on days 1 and 2 of a 21-day cycle. Patients may receive prophylactic pegfilgrastim on day 3 of each cycle, or filgrastim for 5 to 10 days, per investigator's discretion. Patients can receive a maximum of 6 cycles of therapy.
Interventions
DRUGBrentuximab Vedotin
Dose escalation in phase I of the study from 1.2-1.8 mg/kg, IV infusions over 30 minutes on day 1 of each 21-day cycle.
DRUGBendamustine
Dose escalation in phase I of the study from 60-100 mg/m2, IV infusion on days 1 and 2 of each 21-day cycle.
DRUGNeulasta
(Non-experimental) Standard procedure prophylactic pegfilgrastim on day 3 of any subsequent cycle after cycle 1, or filgrastim for 5 to 10 days, per investigator's discretion.
Sponsors
Columbia University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed relapsed or refractory HL or ALCL. * Documented CD30+ expression from either original diagnosis or a tumor biopsy in the relapsed setting. * For patients with HL, subjects are eligible after failure or having declined autologous stem cell transplant or at least two prior multi-agent chemotherapy regimens if they are not autologous stem cell transplant candidates. For patients with ALCL, subjects are eligible after failure of at least one prior multi-agent chemotherapy regimen and if they are not eligible for or have declined autologous stem cell transplant. * Must have received first line chemotherapy. No upper limit for the number of prior therapies. * Patients with prior autologous or allogeneic stem cell transplant are eligible as long as they meet all other criteria. * Measurable or evaluable disease, as defined in 2008 Revised Response Criteria for Malignant Lymphoma(33) * Age \> or = 18 years * ECOG performance status 0,1 or 2 * Patient's must have adequate organ and marrow function as defined below * Absolute neutrophil count \> or = 1,000 (1.0 x 109/L) * Platelets \> or = 50,000 (50 x 109/L) * Total Bilirubin \< or = 1.5 x institutional limits unless documented Gilbert's syndrome (then \< 2.5 x institutional upper limit) * AST (SGOT)/ALT (SGPT) \< or = 2.0 x institutional upper limit of normal (unless known hepatic involvement then \< 3.5 x institutional upper limit) * Creatinine within normal institutional limits OR creatinine clearance \> or = 50mL/min for patients with creatinine levels above institutional normal * If female of childbearing age, negative serum pregnancy test within 7 days prior to the first dose of brentuximab vedotin in this study * Must be willing to use contraception during the study, and for 30 days following the last dose of study drug. * Able to understand and to sign a written consent document
Exclusion criteria
* Prior treatment with brentuximab vedotin and bendamustine in combination. May have received prior therapy with brentuximab vedotin or bendamustine separately. * Received either brentuximab vedotin or bendamustine within 3 months of receiving their first dose of protocol based therapy. * If brentuximab vedotin or bendamustine was previously received, had disease progression during the first 3 cycles of either brentuximab vedotin or bendamustine. * Systemic steroids that have not been stabilized to the equivalent of \< 10 mg/day of prednisone 7 days prior to the initiation of the trial. * ANY concurrent investigational agents. * Exposure to chemotherapy, radiotherapy, biologics or investigational agents within 3 weeks prior enrollment in the study. * Known cerebral or meningeal disease. * Active concurrent malignancy (except non-melanoma skin cancer or carcinoma in situ of the cervix). If there is a history of prior malignancy the patients must be disease free and off treatment for \> or = 3 years. * Uncontrolled intercurrent illness including but not limited to: ongoing or active infection, systemic congestive heart failure Class III or IV by NYHA criteria, unstable angina pectoris, or cardiac arrhythmia, or in patients status post allogeneic transplantation with uncontrolled graft versus host disease (GVHD). * Pre-existing neuropathy grade III or greater. * Pregnant or nursing. * Known hypersensitivity to brentuximab vedotin, bendamustine, or mannitol. * Known Human Immunodeficiency Virus (HIV) positive, or hepatitis A, hepatitis B or hepatitis C; if hepatitis Bsurface antigen positive or Bcore antibody positive must have normal liver function tests and be willing and able to take anti-hepatitis medication such as lamivudine or equivalent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) of Brentuximab Vedotin in Combination of Brentuximab Vedotin and Bendamustine (Phase 1) | 21 days | This is to measure the highest dose that does not cause unacceptable side effects with the combination of brentuximab vedotin and bendamustine. |
| Maximum Tolerated Dose (MTD) of Bendamustine in Combination of Brentuximab Vedotin and Bendamustine (Phase 1) | 21 days | This is to measure the highest dose that does not cause unacceptable side effects with the combination of brentuximab vedotin and bendamustine. |
| Number of Participants With Dose Limiting Toxicities (DLT) of Brentuximab Vedotin and Bendamustine in Phase 1 | 21 days | DLT is defined as any missed dose within cycle 1 or toxicity that was possibly related to the study drug occurring up to 7 days after completion of cycle 1 that resulted in a delay of initiation of cycle 2; grade 4 neutropenia that did not resolve to grade 2 or lower within 7 days; grade 4 thrombocytopenia lasting more than 7 days; grade 3 febrile neutropenia (absolute neutrophil count of \<1000 cells per μL with a single temperature of \>38·3°C or a sustained temperature of ≥38°C for \>1 h); and any grade 3 or worse non-haematological toxicity, with the specific exception of nausea, vomiting, diarrhoea, or dehydration lasting for more than 48 h in the setting of inadequate compliance with supportive care measures or grade 3 hypercholesterolaemia, hypertriglyceridaemia, constipation, or fatigue. |
| Overall Response Rate for the Combination of Brentuximab Vedotin and Bendamustine | Up to 3 years | The number of subjects whose cancer shrinks or disappears after study treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DoR) in Phase 1 | Up to 50 months | Duration of response is defined as the time from documentation of a response to treatment to the first documentation of tumor progression, or death from any cause, whichever occurred first. |
| Progression Free Survival (PFS) in Phase 1 | Up to 50 months | The length of time during and after the study treatment that a subject lives with the disease but it does not get worse. |
| Overall Survival (OS) in Phase 1 | Up to 50 months | The length of time from either the date of diagnosis or the start of study treatment that subjects diagnosed with the disease are still alive. |
Countries
Canada, United States
Contacts
PRINCIPAL_INVESTIGATOROwen A O'Connor, MD, Ph.D.
Columbia University
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 44 years STANDARD_DEVIATION 10.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 6 Participants |
| Race (NIH/OMB) Black or African American | 1 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 | 10 Participants |
| Race (NIH/OMB) White | 44 Participants |
| Region of Enrollment Canada | 26 Participants |
| Region of Enrollment United States | 2 Participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 7 | 2 / 3 | 2 / 7 | 6 / 11 | 7 / 37 |
| other Total, other adverse events | 7 / 7 | 3 / 3 | 7 / 7 | 11 / 11 | 35 / 37 |
| serious Total, serious adverse events | 3 / 7 | 0 / 3 | 2 / 7 | 5 / 11 | 12 / 37 |
Outcome results
None listed