Combination Chemotherapy and Donor Stem Cell Transplant Followed by Ixazomib Citrate Maintenance Therapy in Treating Patients With Relapsed High-Risk Multiple Myeloma
Condition: Plasma Cell Leukemia; Recurrent Plasma Cell Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Leukemia, Plasma Cell
Study type: Interventional
Phase: Phase 1

Summary: 
      This phase Ib trial studies the side effects of combination chemotherapy and donor stem cell
      transplant followed by ixazomib citrate maintenance therapy in treating patients with
      multiple myeloma that has returned after a period of improvement and is likely to recur (come
      back), or spread. Giving chemotherapy before a donor peripheral blood stem cell transplant
      helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem
      cells) and cancer cells. When the healthy stem cells from a donor are infused into the
      patient they may help the patient's bone marrow make stem cells, red blood cells, white blood
      cells, and platelets. Giving ixazomib citrate after the transplant may improve the overall
      treatment outcome without causing additional toxicities.
    

Detailed description: 
      PRIMARY OBJECTIVES:

      I. Safety of BEAM (carmustine, cytarabine, etoposide, melphalan) allogeneic transplant within
      100 days, defined as the day 100 transplant related mortality (TRM).

      II. Safety of oral ixazomib maintenance therapy from day 100 post allogeneic transplant up to
      2 years, defined by the incidence of grade III-IV acute (or overlap) graft-versus-host
      disease (GvHD) and grade III-IV ixazomib related toxicity.

      OUTLINE:

      BEAM CONDITIONING REGIMEN: Patients receive carmustine on day -6, cytarabine and etoposide on
      days -5 to -2, and melphalan on day -1.

      PERIPHERAL BLOOD STEM CELL TRANSPLANT: Patients undergo allogeneic peripheral blood stem cell
      transplantation on day 0.

      GVHD PROPHYLAXIS: Patients receive tacrolimus intravenously (IV) or orally (PO) on days -2 to
      at least 6 months with a taper as early as 3 months post-transplant and methotrexate IV on
      days 1, 3, 6, and 11.

      MAINTENANCE THERAPY: Beginning between days 100 and 180 post-transplant, patients receive
      ixazomib PO on days 1 and 14 or days 1, 8, and 15 if the principal investigator deems it
      medically important. Treatment repeats every 28 days for up to 24 cycles in the absence of
      disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days through 4 months
      post last dose of ixazomib.
    

Intervention name(s): Allogeneic Hematopoietic Stem Cell Transplantation; Carmustine; Cytarabine; Etoposide; Ixazomib Citrate; Melphalan; Methotrexate; Peripheral Blood Stem Cell Transplantation; Quality-of-Life Assessment; Tacrolimus
Intervention type(s): Procedure; Drug; Drug; Drug; Drug; Drug; Drug; Procedure; Other; Drug
Intervention description(s): Undergo allogeneic peripheral blood stem cell transplantation; Given BEAM chemotherapy; Given BEAM chemotherapy; Given BEAM chemotherapy; Given PO; Given BEAM chemotherapy; Given IV; Undergo allogeneic peripheral blood stem cell transplantation; Ancillary studies; Given IV or PO
Other intervention name(s): Allogeneic Hematopoietic Cell Transplantation; Allogeneic Stem Cell Transplantation; HSC; HSCT; Stem Cell Transplantation, Allogeneic; BCNU; Becenum; Becenun; BiCNU; Bis(chloroethyl) Nitrosourea; Bis-Chloronitrosourea; Carmubris; Carmustin; Carmustinum; FDA 0345; N,N''-Bis(2-chloroethyl)-N-nitrosourea; Nitrourean; Nitrumon; SK 27702; SRI 1720; WR-139021; .beta.-Cytosine arabinoside; 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-.beta.-D-Arabinofuranosylcytosine; 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-Beta-D-arabinofuranosylcytosine; 1.beta.-D-Arabinofuranosylcytosine; 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-; 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-; Alexan; Ara-C; ARA-cell; Arabine; Arabinofuranosylcytosine; Arabinosylcytosine; Aracytidine; Aracytin; Aracytine; Beta-cytosine Arabinoside; CHX-3311; Cytarabinum; Cytarbel; Cytosar; Cytosine Arabinoside; Cytosine-.beta.-arabinoside; Cytosine-beta-arabinoside; Erpalfa; Starasid; Tarabine PFS; U 19920; U-19920; Udicil; WR-28453; Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP-16; VP-16-213; VP16; MLN-9708; MLN9708; Ninlaro; Alanine Nitrogen Mustard; CB-3025; L-PAM; L-Phenylalanine Mustard; L-sarcolysin; L-Sarcolysin Phenylalanine mustard; L-Sarcolysine; Melphalanum; Phenylalanine Mustard; Phenylalanine Nitrogen Mustard; Sarcoclorin; Sarkolysin; WR-19813; Abitrexate; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex; Folex PFS; Lantarel; Ledertrexate; Lumexon; Maxtrex; Medsatrexate; Metex; Methoblastin; Methotrexate LPF; Methotrexate Methylaminopterin; Methotrexatum; Metotrexato; Metrotex; Mexate; Mexate-AQ; MTX; Novatrex; Rheumatrex; Texate; Tremetex; Trexeron; Trixilem; WR-19039; PBPC transplantation; PBSCT; Peripheral Blood Progenitor Cell Transplantation; peripheral stem cell support; Peripheral Stem Cell Transplant; Peripheral Stem Cell Transplantation; Quality of Life Assessment; FK 506; Fujimycin; Hecoria; Prograf; Protopic
Intervention MeSH terms: Cytarabine; Methotrexate; Etoposide; Etoposide phosphate; Melphalan; Mechlorethamine; Carmustine; Ixazomib; Podophyllotoxin; Nitrogen Mustard Compounds; Tacrolimus; Glycine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: BEAM; allogeneic; myeloma; ixazomib; transplant; plasma cell leukemia