Multiple Myeloma
Conditions
Brief summary
This is a phase II, single-arm, open-label study in subjects with relapsed and/or refractory multiple myeloma (RRMM) comparing Pembrolizumab (Pembro) in combination with Daratumumab (Dara) to the historical control of Daratumumab.
Detailed description
Heavily pre-treated multiple myeloma patients who are treated with single agent daratumumab have been reported to have median PFS of 4 months. A median PFS of 4 months corresponds to an 8-month progression-free survival rate of 25% (based on the exponential survival distribution). For this population of patients treated with Daratumumab and Pembrolizumab, the aim is to improve the 8-month PFS rate to 50%. Thirty-three RRMM patients who have received ≥ 3 lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) will be eligible for enrollment. Sixteen (16) subjects will be enrolled in the first stage, and if at least 5 of the 16 patients are alive and progression free at 8 months, an additional 17 subjects will be enrolled.
Interventions
DRUGPembrolizumab
Experimental
Sponsors
Merck Sharp & Dohme LLC
Wake Forest University Health Sciences
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
Subjects must meet all of the following inclusion and
Exclusion criteria
to participate in the trial. 1. Written informed consent and HIPAA authorization for release of personal health information. 2. Age ≥ 18 years at the time of consent. 3. ECOG Performance Status of ≤ 1. 4. Documented symptomatic/active multiple myeloma with measurable disease that has previously responded to therapy (partial response or better by IMWG criteria) and since relapsed or is refractory to the last line of therapy. Refractory disease is defined as evidence of progressive disease per IMWG criteria within 60 days (measured from the end of the last cycle) after completing treatment with the last anti-myeloma drug regimen. Note: measurable disease is defined as * Serum monoclonal protein level ≥ 0.5 g/dL for IgG, IgA, or IgM disease * Monoclonal protein or total serum IgD ≥ 0.5 g/dL for IgD disease * Urinary M-protein excretion of ≥ 200 mg over a 24-hour period * Involved free light chain level ≥ 10 mg/dL, along with an abnormal free light chain ratio 5. Subjects must have a documented history of relapsed and/or refractory multiple myeloma with 3 or more prior lines of therapy. 6. Subjects must have had prior exposure to daratumumab in one of the prior lines of therapy. 7. Prior cancer treatment, including chemotherapy and radiation therapy, must be completed at least 14 days prior to enrollment and the subject must have recovered from all reversible acute toxic effects of the regimen to their previous baseline or ≤ Grade 1. Exceptions include alopecia (all grades) and neuropathy (grade 1 with controlled pain, grade 2 without pain). 8. Demonstrate adequate organ function as defined below; all screening labs to be obtained within 3 days prior to initiating study treatment: * Absolute neutrophil count (ANC) ≥ 1.0 x 109/L * Platelets ≥ 75 x 109/L * Hemoglobin ≥ 8 g/dL or 4.96 mmol/L * Calculated creatinine clearance ≥ 30 mL/min/1.73m2 * Corrected serum calcium ≤ 14.0 mg/dL * Serum total bilirubin ≤ 1.5 X ULN OR * Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN * AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN * Activated Partial Thromboplastin Time (aPTT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants ≤1.5 X ULN unless subject is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants 9. Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study treatment. If a urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. 10. As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 8-Month Progression-Free Survival (PFS8) | 8 months | PFS8 will be determined for each subject as a binary variable indicating whether or not the subject is alive and progression free at 8 months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Complete Response (CR) Rate | up to 5 years | CR will be determined for each subject as a binary variable indicating whether or not the specific level of response was achieved. |
| Stringent Complete Response (sCR) Rate | up to 5 years | sCR will be determined for each subject as a binary variable indicating whether or not the specific level of response was achieved. |
| Clinical Benefit Rate (CBR) | up to 5 years | CBR (achieving a minimal response or better) will be determined for each subject as a binary variable indicating whether or not the specific level of response was achieved. |
| Overall Response Rate (ORR) | up to 5 years | ORR (achieving a PR or better) will be determined for each subject as a binary variable indicating whether or not the specific level of response was achieved. |
| Overall Survival (OS) | up to 5 years | OS is defined as the duration from initiation of study treatment to the date of death from any cause. |
| Time to Best Response (TTBR) | up to 5 years | TTBR is defined as the time from the start of study treatment to the time when the best response of MR or better was achieved. |
| Duration of Response (DOR) | up to 5 years | DoR will be calculated for those subjects who achieve a PR or better and is defined as the time first occurrence of PR (or better) until the time of disease progression or death. |
| Progression-Free Survival (PFS) | up to 5 years | PFS is defined as the duration of time from the initiation of study treatment to first occurrence of either progressive disease or death. |
| Time to First Response (TTFR) | up to 5 years | TTFR is defined as the time from the start of study treatment to the time when the first occurrence of a MR or better was achieved. |
Outcome results
None listed