allogeneic stem cell transplantation for patients with multiple myeloma

Conditions: Multiple Myeloma; Myeloma-Multiple

Summary: 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.


Eligibility criteria:
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.