Smoldering Plasma Cell Myeloma
Conditions
Brief summary
This pilot early phase I trial studies pembrolizumab in treating patients with slow growing (smoldering) multiple myeloma with intermediate or high-risk of spreading. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Detailed description
PRIMARY OBJECTIVE: I. To determine the overall response rate after 8 cycles of treatment according to the International Myeloma Working Group Criteria (IMWG). SECONDARY OBJECTIVES: I. To determine time to progression to multiple myeloma (TTP) at 30 months from study entry. II. To determine overall survival (OS). III. To determine duration of response (DOR). IV. To determine the clinical benefit rate (CBR) after 8 cycles of treatment according to the modified IMWG Criteria for multiple myeloma (MM). V. To evaluate safety and tolerability of single agent treatment in this population. EXPLORATORY OBJECTIVES: I. Rate of minimal residual disease (MRD) negativity at complete remission (CR). II. Molecular profiling (including whole exome sequencing and gene expression profiling) and cellular (including flow cytometry) profiling at baseline and/or at progression using bone marrow aspirate samples and peripheral blood. III. Immunophenotypic characterization of dendritic, T-, B-, natural killer (NK)- and natural killer T (NKT)-cells, and inhibitory/activation markers on tumor cells at baseline and at completion of 8 cycles of therapy in bone marrow aspirate samples and/or peripheral blood. IV. Evaluation of changes in PD-L1 and PD-1 expression at baseline/end of 8 cycles of treatment and correlate with clinical response. OUTLINE: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Treatment repeats every 21 days for up to 24 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 6-12 months.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
BIOLOGICALPembrolizumab
Given IV
Sponsors
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
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
* Adult patients with intermediate or high-risk smoldering multiple myeloma (SMM) are eligible; patients need to have clonal bone marrow plasma cells \>= 10% and/or monoclonal spike in blood of \>= 3 g/dL and/or monoclonal urine component (Bence jones proteinuria) \>= 500 mg/24 hours and need to meet subject inclusion criteria and
Exclusion criteria
as per below * Patients must have histologically confirmed SMM based on the following criteria: * (A) Mayo clinic criteria (patient must have at least 2 risk factors present): * 1\. Bone marrow core biopsy plasma cell involvement by cluster of differentiation (CD)138 immunohistochemistry \>= 10% * 2\. Monoclonal spike \>= 3 g/dL * 3\. Free light chain ratio in serum \< 0.125 or \> 8; \*2 of 3 risk factors: intermediate risk for progression at a rate of 51% at 5 years, \*3 of 3 risk factors: high risk for progression at a rate of 76% at 5 years * OR (B) Programa para el Tratamiento de Hemopatias Malignas (PETHEMA) criteria (patient must have at least 1 risk factor present) * 1\. \>= 95% abnormal plasma cells/total plasma cells in bone marrow compartment * 2\. Immunoparesis \*1 of 2 risk factors: intermediate risk for progression at a rate of 46% at 5 years, \*2 of 2 risk factors: high risk for progression at a rate of 72% at 5 years * OR (C) Southwestern Oncology Group (SWOG) criteria (patient must have 2 risk factors present or one risk factor if this risk factor is a 70-gene signature (GEP70) score of \> 37.2) * 1\. Monoclonal spike \>= 3 g/dL * 2\. Involved free light chain \>= 25 mg/dL * 3\. GEP70 risk score \> 37.2 \*\>= 2 risk factors: high risk of progression at a rate of 70% at 2 years\*; we would also include patients with 1 risk factor as long as this risk factor is GEP70 risk score \> 37.2 since patients with this risk factor have an intermediate risk of progression at a rate of 50% at 2 years * Creatinine clearance \>= 50 ml/min; creatinine clearance (CrCl) will be calculated by Cockcroft-Gault method * Eastern Cooperative Oncology Group (ECOG) performance status 0-1 * Absolute neutrophil count (ANC) \>= 1.0 x 10\^9 /L * Hemoglobin \>= 10 g/dL * Platelet count \>= 50 x 10\^9/L * Bilirubin \< 1.5 x the upper limit of normal (ULN) * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3.0 x ULN * Subjects must be able to give informed consent * Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication; if the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required * Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication; subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year * Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | From cycle 1 to cycle 8, up to 168 days | Overall response rate is defined as patients who have achieved partial response or higher as described per IMWG criteria for multiple myeloma after 8 cycles of therapy with pembrolizumab. Will be measured according to International Myeloma Working Group Criteria (IMWG) criteria. Response rate will be estimated accordingly. Each cycle has a duration of 21 days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants That Had Progression to Multiple Myeloma | At 30 months from study entry | Progressive disease assessed by IMWG criteria for multiple myeloma after 8 cycles of therapy with pembrolizumab. |
| Clinical Benefit Rate | From cycle 1 to cycle 8, up to 168 days | Minor response or better assessed by IMWG criteria for multiple myeloma after 8 cycles of therapy with pembrolizumab |
| Overall Survival | Time of start of treatment to death from any cause up to 2 years and 6 months | Participants in a study or treatment group who are still alive for a certain period of time after they were diagnosed with or started treatment for a disease |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORNeeraj Saini, MD
M.D. Anderson Cancer Center
Participant flow
Recruitment details
Enrollment period was between July 2016 and August 2017
Pre-assignment details
20 participants were consented. 13 participants were treated at MD Anderson Cancer Center. An additional participant started stage 2 that did not participate in Stage 1"
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Pembrolizumab) Pembrolizumab 200 mg, 30 minute IV infusion every 21 days up to 24 cycles if equal or higher than minor response and without serious adverse events after 8 cycles | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | Treatment (Pembrolizumab) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 68 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Myeloma related lab Bence Jones urine protein | 6 mg/day |
| Myeloma related lab Bone marrow biopsy plasma cells | 30 percentage of plasma cells |
| Myeloma related lab Lactate dehydrogenase | 439 u/L |
| Myeloma related labs B2 microglobulin | 1.9 mg/L |
| Myeloma related labs Calcium | 9.3 mg/dL |
| Myeloma related labs Creatinine | .88 mg/dL |
| Myeloma related labs Free Light Chains (FLCs) ratio | 12.27 ratio |
| Myeloma related labs Hemoglobin | 12.4 gm/dL |
| Myeloma related labs Involved:Uninvolved ratio | 17.95 ratio |
| Myeloma related labs Kappa free light chain | 127.04 mg/L |
| Myeloma related labs Lambda free light chain | 8.08 mg/L |
| Myeloma related labs Serum paraprotein | 1.9 gm/dL |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 13 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 13 |
| other Total, other adverse events | 13 / 13 |
| serious Total, serious adverse events | 3 / 13 |
Outcome results
Primary
Overall Response Rate (ORR)
Overall response rate is defined as patients who have achieved partial response or higher as described per IMWG criteria for multiple myeloma after 8 cycles of therapy with pembrolizumab. Will be measured according to International Myeloma Working Group Criteria (IMWG) criteria. Response rate will be estimated accordingly. Each cycle has a duration of 21 days.
Time frame: From cycle 1 to cycle 8, up to 168 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Pembrolizumab) | Overall Response Rate (ORR) | 1 Participants |
Secondary
Clinical Benefit Rate
Minor response or better assessed by IMWG criteria for multiple myeloma after 8 cycles of therapy with pembrolizumab
Time frame: From cycle 1 to cycle 8, up to 168 days
Population: Clinical benefit rate is described as minor response or better assessed by IMWG criteria for multiple myeloma after 8 cycles of therapy with pembrolizumab. 1 participant of 13 achieved sCR
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Pembrolizumab) | Clinical Benefit Rate | 1 Participants |
Secondary
Number of Participants That Had Progression to Multiple Myeloma
Progressive disease assessed by IMWG criteria for multiple myeloma after 8 cycles of therapy with pembrolizumab.
Time frame: At 30 months from study entry
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Pembrolizumab) | Number of Participants That Had Progression to Multiple Myeloma | 3 Participants |
Secondary
Overall Survival
Participants in a study or treatment group who are still alive for a certain period of time after they were diagnosed with or started treatment for a disease
Time frame: Time of start of treatment to death from any cause up to 2 years and 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Pembrolizumab) | Overall Survival | 12 Participants |