Overview

Pembrolizumab for Smoldering Multiple Myeloma (SMM)

Status:
Recruiting
Trial end date:
0000-00-00
Target enrollment:
16
Participant gender:
Both
Summary
The goal of this clinical research study is to learn if Keytruda (pembrolizumab) can help to control intermediate- or high-risk smoldering multiple myeloma (SMM). The safety of this drug will also be studied.
Phase:
N/A
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
M.D. Anderson Cancer Center
Collaborator:
Merck Sharp & Dohme Corp.
Treatments:
Pembrolizumab
Last Updated:
2016-12-15
Criteria
Inclusion Criteria:

1. Adult patients (age >/=18 years old) with intermediate or high-risk 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.

2. 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 CD138 immunohistochemistry >/=10% 2.
Monoclonal spike >/=3g/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

3. OR (B) 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

4. OR (C) SWOG criteria (patient must have 2 risk factors present or one risk factor if
this risk factor if a 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.

5. Creatinine clearance >/= 50 ml/min. CrCl will be calculated by Cockcroft-Gault
method. CrCl (calculated) = (140 - Age) x Mass (in kilograms) x [0.85 if Female] / 72
x Serum Creatinine (in mg/dL). If calculated CrCl based on Cockcroft-Gault method is
< 50 mL/min, patient will have a 24 hr urine collection to measure CrCl. The measured
CrCl must also be >/= 50 ml/min

6. Eastern Cooperative Oncology Group (ECOG) performance status 0-1

7. Absolute neutrophil count (ANC) >/= 1.0 x 10^9 /L, hemoglobin >/= 10 g/dL and
platelet count >/= 50 x 10^9/L

8. Adequate hepatic function with bilirubin < 1.5 x the ULN, and AST and ALT < 3.0 x
ULN.

9. Subjects must be able to give informed consent

10. 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.

11. 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.

12. 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.

Exclusion Criteria:

1. Evidence of myeloma defining events or biomarkers of malignancy due to underlying
plasma cell proliferative disorder meeting at least one of the following 1)
Hypercalcemia: serum calcium >0.25 mmol/L (>1 mg/dL) higher than the upper limit of
normal or > 2.75 mmol/L (> 11 mg/dL) 2) Renal Insufficiency: creatinine clearance <
40 ml/min or serum creatinine > 2 mg/dL 3) Anemia: hemoglobin value <10 g/dL or 2
g/dL < normal reference 4) Bone lesions: one or more osteolytic lesions on skeletal
radiography, computerized tomography (CT) or 2-deoxy-2[F-18] fluoro-D-glucose
positron emission tomography CT (PET-CT). 5) Clonal bone marrow plasma cell
percentage >/= 60% 6) Involved: uninvolved serum free light chain ratio >/= 100
measured by Freelite assay (The Binding Site Group, Birmingham, UK) 7) >1 focal
lesions on MRI studies (each focal lesion must be 5 mm or more in size), if
clinically indicated

2. Prior or concurrent systemic treatment for SMM. a) Bisphosphonates are permitted. b)
Treatment with corticosteroids is not permitted c) Radiotherapy is not permitted. d)
Prior treatment for smoldering multiple myeloma with chemotherapy agents approved for
the treatment of multiple myeloma is not permitted.

3. Plasma cell leukemia

4. Pregnant or lactating females. Because there is a potential risk for adverse events
in nursing infants secondary to treatment of the mother with pembrolizumab,
breastfeeding should be discontinued if the mother is treated with pembrolizumab.
These potential risks may also apply to other agents used in this study.

5. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to the first dose of
trial treatment.

6. Has a known history of active TB (Bacillus Tuberculosis)

7. Hypersensitivity to pembrolizumab or any of its excipients.

8. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
Day 1 or who has not recovered (i.e., due to agents administered more than 4 weeks earlier.

9. Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
skin that has undergone potentially curative therapy or in situ cervical cancer.

10. Has active autoimmune disease that has required systemic treatment in the past 2
years (i.e. with use of disease modifying agents, corticosteroids or
immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or
physiologic corticosteroid replacement therapy for adrenal or pituitary
insufficiency, etc.) is not considered a form of systemic treatment.

11. Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis.

12. Has an active infection requiring systemic therapy.

13. Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the
subject's participation for the full duration of the trial, or is not in the best
interest of the subject to participate, in the opinion of the treating investigator.

14. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.

15. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the pre-screening or screening visit
through 120 days after the last dose of trial treatment.

16. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

17. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

18. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).

19. Has received a live vaccine within 30 days of planned start of study therapy. Note:
Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
attenuated vaccines, and are not allowed.

20. Evidence of interstitial lung disease.