Hodgkin Lymphoma
Conditions
Keywords
Mocetinostat (MGCD0103), Brentuximab Vedotin (SGN-35), Relapsed, Refractory
Brief summary
The purpose of this study is to find out how safe and effective treatment with a new combination of drugs, mocetinostat and brentuximab vedotin, is in treating cancer. There will be 2 parts to this trial: a phase I part and a phase II part. Brentuximab vedotin is approved by the U.S. Food and Drug Administration (FDA) to be given to patients with Hodgkin Lymphoma. Mocetinostat is an experimental drug that has been given to patients with Hodgkin lymphoma in another clinical trial. When given alone, mocetinostat caused lymphoma to shrink in about 1 out of 4 patients with Hodgkin lymphoma. This is the first study that will give mocetinostat and brentuximab vedotin together.
Interventions
DRUGMocetinostat Plus Brentuximab Vedotin
All patients will receive a 1-week lead-in with mocetinostat alone (administered days 1, 3, and 5). Patients with palpable peripheral lymph nodes will undergo FNA before and after this 1 week treatment. Cycle 1 will then begin 15 days (+/-3 days) following initiation of the lead-in.
Sponsors
MethylGene Inc.
Memorial Sloan Kettering Cancer Center
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
* Patients must have histologically confirmed CD30 positive relapsed or refractory Hodgkin lymphoma * Measurable disease, as defined by the International Harmonization Project.14 * Patients must have failed autologous stem cell transplant or at least 2 prior cytotoxic regimens for Hodgkin lymphoma. Patients who have failed only 1 prior cytotoxic regimen for Hodgkin lymphoma are permitted to enroll as long as they are not eligible for autologous stem cell transplant. * Age ≥18 * ECOG performance status ≤2 (Karnofsky ≥60%) * Patients must have normal organ and marrow function as defined below: * absolute neutrophil count ≥1,000/mcL * platelets ≥75,000/mcL * total bilirubin within normal institutional limits or \< 3x the upper limit of normal in patients with Gilbert's disease * AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal * Creatinine ≤1.5 x institutional upper limit of normal OR creatinine clearance ≥40 mL/min/1.73 m2 for patients with creatinine levels above institutional normal. * QTc ≤ 500 ms * The effects of mocetinostat and brentuximab vedotin on the developing human fetus are potentially harmful. For this reason, 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 and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of mocetinostat and brentuximab vedotin administration. * Patients with known HIV infection must have CD4 count greater than 200.
Exclusion criteria
* Presence of a small (or greater size) pericardial effusion; definitions of pericardial effusions by echocardiographic assessment. * Patients who have had chemotherapy or radiotherapy within 3 weeks prior to entering the study * Patients who have not recovered from adverse events due to agents administered more than 3 weeks earlier. * Patients who are receiving any other investigational agents. * Patients with known cerebral or meningeal involvement by lymphoma are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. * History of allergic reactions attributed to compounds of similar chemical or biologic composition to mocetinostat or brentuximab vedotin. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, uncontrolled diabetes, clinically significant pneumonitis, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. * Women who are pregnant or breastfeeding * Previous primary progression or grade 3 toxicity on treatment with brentuximab vedotin * Systemic steroids are allowed as long as they are tapered to the equivalent of 20mg prednisone daily or less by the start of cycle 2. * Platelet or packed red blood cell transfusion within 14 days of pre-treatment evaluation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) | 1 year | For this objective the standard 3+3 dose-escalation scheme will be used. Patients will be accrued to the study in cohorts of 3 (starting with dose level 1). For any given dose an initial cohort of 3 patients will be treated at that dose. The dose level will be escalated if none of the 3 patients exhibits any DLT |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | 1 year | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dose Level 1: 50mg Mocetinostat Mocetinostat Plus Brentuximab Vedotin: All patients will receive a 1-week lead-in with mocetinostat alone (administered days 1, 3, and 5). Patients with palpable peripheral lymph nodes will undergo FNA before and after this 1 week treatment. Cycle 1 will then begin 15 days (+/-3 days) following initiation of the lead-in. | 3 |
| Dose Level 2: 70mg Mocetinostat Mocetinostat Plus Brentuximab Vedotin: All patients will receive a 1-week lead-in with mocetinostat alone (administered days 1, 3, and 5). Patients with palpable peripheral lymph nodes will undergo FNA before and after this 1 week treatment. Cycle 1 will then begin 15 days (+/-3 days) following initiation of the lead-in. | 3 |
| Dose Level 3: 90mg Mocetinostat Mocetinostat Plus Brentuximab Vedotin: All patients will receive a 1-week lead-in with mocetinostat alone (administered days 1, 3, and 5). Patients with palpable peripheral lymph nodes will undergo FNA before and after this 1 week treatment. Cycle 1 will then begin 15 days (+/-3 days) following initiation of the lead-in. | 1 |
| Total | 7 |
Baseline characteristics
| Characteristic | Dose Level 3: 90mg Mocetinostat | Dose Level 2: 70mg Mocetinostat | Dose Level 1: 50mg Mocetinostat | Total |
|---|---|---|---|---|
| Age, Continuous | 43 years | 30 years | 43 years | 33 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 2 Participants | 3 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 1 Participants | 3 Participants | 3 Participants | 7 Participants |
| Region of Enrollment United States | 1 Participants | 3 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Female | 0 Participants | 3 Participants | 1 Participants | 4 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 | 1 / 1 |
| other Total, other adverse events | 3 / 3 | 3 / 3 | 1 / 1 |
| serious Total, serious adverse events | 1 / 3 | 0 / 3 | 1 / 1 |
Outcome results
Primary
Maximum Tolerated Dose (MTD)
For this objective the standard 3+3 dose-escalation scheme will be used. Patients will be accrued to the study in cohorts of 3 (starting with dose level 1). For any given dose an initial cohort of 3 patients will be treated at that dose. The dose level will be escalated if none of the 3 patients exhibits any DLT
Time frame: 1 year
Population: Data were not collected
Secondary
Overall Response Rate (ORR)
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Time frame: 1 year
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mocetinostat (MGCD0103) Plus Brentuximab Vedotin (SGN-35) | Overall Response Rate (ORR) | Progression of Disease | 2 Participants |
| Mocetinostat (MGCD0103) Plus Brentuximab Vedotin (SGN-35) | Overall Response Rate (ORR) | Partial Response | 0 Participants |
| Mocetinostat (MGCD0103) Plus Brentuximab Vedotin (SGN-35) | Overall Response Rate (ORR) | Stable Disease | 0 Participants |
| Mocetinostat (MGCD0103) Plus Brentuximab Vedotin (SGN-35) | Overall Response Rate (ORR) | NA - Patient Withdrawal of Consent | 1 Participants |
| Dose Level 2: 70mg Mocetinostat | Overall Response Rate (ORR) | NA - Patient Withdrawal of Consent | 0 Participants |
| Dose Level 2: 70mg Mocetinostat | Overall Response Rate (ORR) | Progression of Disease | 0 Participants |
| Dose Level 2: 70mg Mocetinostat | Overall Response Rate (ORR) | Stable Disease | 1 Participants |
| Dose Level 2: 70mg Mocetinostat | Overall Response Rate (ORR) | Partial Response | 2 Participants |
| Dose Level 3: 90mg Mocetinostat | Overall Response Rate (ORR) | NA - Patient Withdrawal of Consent | 0 Participants |
| Dose Level 3: 90mg Mocetinostat | Overall Response Rate (ORR) | Partial Response | 0 Participants |
| Dose Level 3: 90mg Mocetinostat | Overall Response Rate (ORR) | Stable Disease | 0 Participants |
| Dose Level 3: 90mg Mocetinostat | Overall Response Rate (ORR) | Progression of Disease | 1 Participants |