Allogeneic Stem Cell Transplantation for Patients With Multiple Myeloma
Allogeneic Stem Cell Transplantation for Patients With Multiple Myeloma
The purpose of this study is to develop a novel platform for allo-SCT in multiple myeloma
 (MM) with the idea of maximizing anti-myeloma effect with conditioning and minimizing GvHD
 (graft versus host disease). Specifically, the investigators will use the Flu/Mel
 (fludarabine and melphalan) regimen. For GvHD prophylaxis, the investigators use the Hopkins
 PT-Cy (post-transplant cyclophosphamide) platform with the novelty of adding tocilizumab as
 both an anti-myeloma therapy and as a method to reduce GvHD. IL-6 has an important role in
 promoting the growth of myeloma cells and progression of disease.
Inclusion Criteria:

 -  Histologically confirmed diagnosis of myeloma.

 -  Between 18 and 70 years of age (inclusive).

 -  Karnofsky performance status ≥ 50% or ECOG performance score of ≤ 2 -Completion of
 last anti-myeloma therapy (if any) must occur at least 14 days before conditioning.

 -  Must have an HLA-matched sibling, HLA-matched unrelated donor, or a related
 haploidentical donor:

 -  Available HLA-matched sibling or unrelated donor must meet the following criteria:

 -  At least 18 years of age

 -  HLA donor/recipient match based on at least low-resolution typing per
 institutional standards (syngeneic donors [identical twins] are excluded)

 -  In the investigator's opinion, is in general good health, and medically able to
 tolerate leukapheresis required for harvesting stem cells

 -  No active hepatitis

 -  Negative for HTLV and HIV

 -  Not pregnant

 OR

 -  Available haploidentical donor must meet the following criteria:

 -  Blood-related family member (sibling (full or half), offspring, parent, cousin,
 niece or nephew, aunt or uncle, or grandparent)

 -  At least 18 years of age

 -  HLA-haploidentical donor/recipient match by at least low-resolution typing per
 institutional standards

 -  In the investigator's opinion, is in general good health, and medically able to
 tolerate leukapheresis required for harvesting stem cells

 -  No active hepatitis

 -  Negative for HTLV and HIV

 -  Not pregnant

 -  Normal bone marrow and organ function as defined below within 14 days prior to first
 study drug dose (conditioning regimen):

 -  Total bilirubin ≤ 2.5 mg/dl

 -  AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN

 -  Creatinine ≤ 2.0 x ULN OR estimated creatinine clearance ≥ 30 mL/min/1.73 m2 by
 Cockcroft-Gault Formula (See Appendix C)

 -  Oxygen saturation ≥ 90% on room air

 -  LVEF ≥ 40%

 -  FEV1 and FVC ≥ 40% predicted, DLCOc ≥ 40% predicted

 -  Women of childbearing potential and men must agree to use adequate contraception
 (hormonal or barrier method of birth control, abstinence) prior to study entry through
 Day +100 visit. Should a woman become pregnant or suspect she is pregnant while
 participating in this study, she must inform her treating physician immediately.

 -  Able to understand and willing to sign an IRB approved written informed consent
 document (or that of legally authorized representative, if applicable).

 Exclusion Criteria:

 -  Receiving renal replacement therapy, hemodialysis, or peritoneal dialysis.

 -  Presence of another concurrent malignancy requiring treatment.

 -  History of allergic reactions attributed to compounds of similar chemical or biologic
 composition to melphalan, cyclophosphamide, or other agents used in the study.

 -  Presence of an uncontrolled intercurrent illness including, but not limited to,
 symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or
 psychiatric illness/social situations that would limit compliance with study
 requirements.

 -  Pregnant and/or breastfeeding.

 -  Previous treatment with tocilizumab (TCZ).

 -  Immunization with a live/attenuated vaccine within 28 days prior to conditioning.

 -  Any history of recent serious bacterial, viral, fungal, or other opportunistic
 infections, precluding a stem cell transplant according to the treating physician.

 -  Serologic evidence of HIV

 -  Active infection with Hepatitis A, B, or C. Active infection is defined as serologic
 positivity and elevated liver function tests.

 -  History of tuberculosis

 -  Active infection with EBV as defined as EBV viral load ≥ 10,000 copies per mL of whole
 blood; EBV viral load testing is only required if the patient has clinical signs or
 symptoms suggestive of active EBV infection

 -  Active infection with CMV as defined as CMV viral load ≥ 10,000 copies per mL of whole
 blood; CMV viral load testing is only required if the patient has clinical signs or
 symptoms suggestive of active CMV infection

 -  History of complicated diverticulitis, including fistulae, abscess formation or
 gastrointestinal (GI) perforation.

 -  Pre-existing CNS demyelination or seizure disorders

 -  Major surgery within preceding 8 weeks

 -  Body weight >150kg

 -  History of severe allergic or anaphylactic reactions to human, humanized, or murine
 monoclonal antibodies.