Classic Hodgkin Lymphoma, Hodgkin Lymphoma, Refractory Classic Hodgkin Lymphoma, Relapsed Classical Hodgkin Lymphoma
Conditions
Brief summary
The purpose of this study is to test the safety and efficacy of magrolimab in combination with pembrolizumab in patients with Hodgkin lymphoma.
Detailed description
Primary Objectives: \- To assess the complete remission (CR) rate of magrolimab in combination with pembrolizumab in adult subjects with relapsed or refractory cHL Secondary Objectives: * To assess the safety and tolerability of magrolimab in combination with pembrolizumab in adult subjects with relapsed or refractory cHL * To assess the overall response rate (ORR)
Interventions
DRUGMagrolimab
45 mg/kg with dose escalation starting at 1 mg/kg IV Infusion
DRUGPembrolizumab
200 mg IV infusion
PROCEDUREPET/CT
Scan
Sponsors
Ranjana Advani
Merck Sharp & Dohme LLC
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
* Age ≥ 18 years * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 * Biopsy proven relapsed or refractory cHL * Prior treatment with at least two systemic therapies * Metabolically active measurable disease by PET imaging per the 2014 Lugano criteria * Hemoglobin ≥ 9.5 g/dL * Absolute neutrophil count ≥ 1,000 cells/μL without G-CSF support within 3 weeks prior to enrollment * Platelet count ≥ 75,000 cells/μL * Creatinine clearance \> 40 mL/min per the Cockroft-Gault formula * Total bilirubin \< 1.5 x upper limit of normal (ULN) (or \< 3.0 x ULN and primarily unconjugated in subjects with a history of Gilbert's syndrome) * Negative urine or serum pregnancy test within 30 days of enrollment and within 72 hours before the first administration of magrolimab for women of childbearing potential * Women of childbearing potential must be willing to use at least 1 highly effective method of contraception during the study and continue for 4 months after the last dose of magrolimab * Male subjects who are sexually active with a woman of childbearing potential and who have not had vasectomies must be willing to use a barrier method of contraception during the study and for 4 months after the last dose of magrolimab * Ability to understand and the willingness to sign the written IRB approved informed consent document * Must be willing and able to comply with the clinic visits and procedures outlined in the study protocol
Exclusion criteria
* Prior treatment with a PD-1 inhibitor within 3 months prior to enrollment * Prior treatment with antibodies targeting CD47 or SIRPα2 * Prior allogeneic hematopoietic cell transplantation * Systemic autoimmune disorder on chronic immunosuppression (defined as ≥ 10 mg of prednisone daily) * RBC transfusion dependence, defined as requiring more than 2 units of RBCs during the 4-week period prior to screening * History of hemolytic anemia, autoimmune thrombocytopenia, or Evan's syndrome within the last 3 months * Second malignancy not in complete remission for at least 1 year, excluding fully resected non melanoma skin cancer or localized prostate cancer * Women who are pregnant or breast feeding * HIV or hepatitis B or C infection with active viral replication by PCR * Second malignancy not in complete remission for at least 1 year, excluding fully resected non-melanoma skin cancer or localized prostate cancer * Active cardiac disease including unstable angina, decompensated congestive heart failure, or severe uncontrolled conduction abnormalities * History of non-infectious pneumonitis requiring corticosteroids or current pneumonitis * Significant medical conditions, as assessed by the investigators and IND holder, that would substantially increase the risk benefit ratio of participating in the study * History of psychiatric illness or substance abuse likely to interfere with ability to comply with protocol requirements * Received a live or live attenuated vaccine within 30 days before the first dose of study intervention * Received any anti-cancer therapy within 2 weeks prior to the first dose of study intervention
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response (CR) | Up to 2 years | Each participant's response to treatment will be assessed per the Lugano criteria. The criteria are: * Complete Response (CR): Complete disappearance of all lesions, evidence, and effects of disease * Partial Response (PR): ≥50% decrease in SPD of the 6 largest lesions with no increase in the size of the other nodes; splenic / hepatic nodules regress ≥50%, and with no new sites of disease * Stable disease (SD): less than PR. * Progressive disease (PD): sum of the product of dimensions (SPD) of lesions increased ≥50% from smallest value The outcome will be reported as the number of participants with a CR after 4 and 8 cycles of treatment (4 and 8 months), and if CR is achieved anytime within 2 years ("overall"). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Magrolimab Related Adverse Events | up to 4 months | Magrolimab safety and tolerability will be assessed on the basis of magrolimab related adverse events occurring within 4 cycles of treatment (4 months). The outcome will be reported as the number of magrolimab related adverse events judged mild (Grade 1), moderate (Grade 2), severe (Grade 3), life threatening (Grade 4), or fatal (Grade 5), numbers without dispersion. |
| Overall Response (OR) | up to 8 months | Overall response (OR) is defined as the sum of participants who achieve a complete response (CR) plus the number of participants who achieve a partial response (PR). Treatment response will be assessed per the Lugano criteria (aka the Cheson criteria). The criteria are: * CR: Complete disappearance of all lesions, evidence, and effects of disease * PR: ≥50% decrease in SPD of the 6 largest lesions with no increase in the size of the other nodes; splenic / hepatic nodules regress ≥50%, and with no new sites of disease * Stable disease (SD): less than PR. * Progressive disease (PD): sum of the product of dimensions (SPD) of lesions increased ≥50% from smallest value The outcome will be reported as the number of participants with either a CR or a PR after 4 and 8 cycles of treatment (4 and 8 months). For participants who undergo a subsequent stem cell transplant, the value will be recorded as the time to transplant (censored). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRanjana H Advani, MD
Stanford Universiy
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 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 | 2 Participants |
| Race (NIH/OMB) White | 5 Participants |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 8 |
| other Total, other adverse events | 8 / 8 |
| serious Total, serious adverse events | 2 / 8 |
Outcome results
None listed