Siltuximab to Decrease Symptom Burden After Autologous Stem Cell Transplantation for Patients With Multiple Myeloma and AL Amyloidosis
Siltuximab to Decrease Symptom Burden After Autologous Stem Cell Transplantation for Patients With Multiple Myeloma and AL Amyloidosis
Autologous stem cell transplant is beneficial to patients who are diagnosed with multiple
 myeloma or systemic amyloidosis. However, undesired symptoms such as weakness, fatigue,
 nausea, pain and sleep disturbance after transplant can contribute to complications and
 increase the how long the patient is in the hospital, especially in patients age 60-75.
 Research has shown that the development and the intensity of these symptoms are closely
 associated with an increase in a protein called a cytokine which is involved in the
 inflammatory response in the human body. One of the cytokines is called Interleukin-6 or
 IL-6.Therefore, this study will investigate if blocking IL-6 with an agent called siltuximab,
 administered before and after transplant, will decrease the symptom burden after transplant
 to improve quality of life and recovery in the immediate post-transplant period.
Inclusion Criteria:

 -  Patients with histologically-confirmed symptomatic multiple myeloma or AL amyloidosis
 undergoing autologous HCT with melphalan 140 or 200 mg/m2

 -  Age 60 through 75 years

 -  Have at least 3 million x 10e6 CD34+ cells/kg to be infused

 -  Diffusion capacity >45% (adjusted for hemoglobin) as predicted by pulmonary function
 testing.

 -  KPS performance status ≥ 60% or ECOG Performance Status score of 0-2

 -  Clinical laboratory values meeting the following criteria within 4 weeks before
 enrollment:

 -  LVEF >45% by MUGA or rest ECHO

 -  Diffusion capacity >45% (adjusted for hemoglobin) as predicted pulmonary function
 testing

 -  Platelet count ≥ 20 x 10^9/L

 -  ALT and AST ≤ 2.5 x ULN

 -  Total bilirubin ≤ 2.5 x ULN; except if the elevation is due to Gilbert's syndrome

 -  Calculated creatinine clearance > 40 mL/min

 -  Before enrollment, all women are expected to be not of childbearing potential as they
 will be age 60-75>:

 -  Not of childbearing potential: postmenopausal (>45 years of age with amenorrhea
 for at least 12 months or any age with amenorrhea for at least 6 months and a
 serum follicle stimulating hormone (FSH) level >40 IU/mL); permanently sterilized
 (eg, tubal occlusion, hysterectomy, bilateral salpingectomy); or otherwise be
 incapable of pregnancy

 -  Of childbearing potential and practicing (during the study and for 3 months after
 receiving the last dose of study agent) a highly effective method of birth
 control consistent with local regulations regarding the use of birth control
 methods for subjects participating in clinical studies: eg, established use of
 oral, injected or implanted hormonal methods of contraception; placement of an
 intrauterine device (IUD) or intrauterine system (IUS); barrier methods: condom
 with spermicidal foam/gel/film/cream/suppository or occlusive cap (diaphragm or
 cervical/vault caps) with spermicidal foam/gel/film/cream/suppository; male
 partner sterilization (the vasectomized partner should be the sole partner for
 that subject); true abstinence (when this is in line with the preferred and usual
 lifestyle of the subject)

 -  A woman of childbearing potential must have a negative serum (β-human chorionic
 gonadotropin [β-hCG]) pregnancy test at screening

 -  During the study and for 3 months after receiving the last dose of study agent, a
 woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted
 reproduction

 -  Note: If the childbearing potential changes after start of the study (eg, woman
 who is not heterosexually active becomes active) a woman must begin a highly
 effective method of birth control, as described above.

 -  A man who is sexually active with a woman of childbearing potential and has not had a
 vasectomy must agree to use a barrier method of birth control eg, either condom with
 spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm
 or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository, and all men
 must also not donate sperm during the study and for 3 months after receiving the last
 dose of study drug

 Exclusion Criteria:

 -  Prior exposure to agents targeting IL-6 or the IL-6 receptor

 -  Other malignancy within the past 2 years, except for the following if treated and not
 active: basal cell or nonmetastatic squamous cell carcinoma of the skin, cervical
 carcinoma in situ or International Federation of Gynecology and Obstetrics (FIGO)
 Stage 1 carcinoma of the cervix

 -  Concurrent medical condition or disease (eg, autoimmune disease, active systemic
 Infection) that is likely to interfere with study procedures or results, or that in
 the opinion of the investigator would constitute a hazard for participating in the
 study

 -  Vaccination with live attenuated vaccines within 4 weeks of first study agent
 administration

 -  Clinically significant infection, including known HIV or hepatitis C infection, or
 known hepatitis B (Hep B) surface antigen positivity. Patients with Hep B Core
 positivity can be enrolled if the Hep B PCR is negative, and they are on antiviral
 suppression.

 -  Received an investigational drug (including investigational vaccines) or used an
 invasive investigational medical device within 14 days or 5 half lives before
 enrollment or is currently enrolled in the treatment stage of an investigational study

 -  Had hospitalization for infection or major surgery (eg, requiring general anesthesia)
 within 2 weeks before enrollment or have not fully recovered from surgery. Note:
 subjects with surgical procedures conducted under local anesthesia may participate

 -  A woman who is pregnant or breast-feeding, or a woman who is planning to become
 pregnant or a man who plans to father a child while enrolled in this study or within 3
 months after the last dose of study agent.