Combination Chemotherapy and Donor Stem Cell Transplant Followed by Ixazomib Citrate Maintenance Therapy in Treating Patients With Relapsed High-Risk Multiple Myeloma

NCT02504359 | Completed Phase 1 DMC

• 3 other identifiers: IRB00011097NCI-2015-01065HEM-14099-LM
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Plasma Cell Leukemia; Recurrent Plasma Cell Myeloma

Keywords

BEAM; allogeneic; myeloma; ixazomib; transplant; plasma cell leukemia

Outcome Measures

Primary Outcomes (2)

• Transplant related mortality (TRM)

  Time to event analysis will be conducted to estimate day 100 TRM and its confidence interval among those who receive carmustine, cytarabine, etoposide, melphalan (BEAM) allogeneic transplantation.

  At day 100

• Incidence of grade III-IV acute (or overlap) graft versus host disease (GvHD) and ixazomib related grade III-IV toxicity

  Time to event analysis will be conducted to estimate the incidence of acute (or overlap) GvHD and grade III-IV treatment related toxicity among those who receive ixazomib maintenance therapy, accounting for possible competing risks and events. All treatment related toxicity will be tabulated and summarized by severity and major organ categories defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

  Up to 2 years

Study Arms (1)

Treatment (BEAM allogeneic transplant, ixazomib)

EXPERIMENTAL

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 IV or 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.

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Carmustine; Drug: Cytarabine; Drug: Etoposide; Drug: Ixazomib Citrate; Drug: Melphalan; Drug: Methotrexate; Procedure: Peripheral Blood Stem Cell Transplantation; Other: Quality-of-Life Assessment; Drug: Tacrolimus

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allogeneic peripheral blood stem cell transplantation

Also known as: Allogeneic Hematopoietic Cell Transplantation, Allogeneic Stem Cell Transplantation, HSC, HSCT, Stem Cell Transplantation, Allogeneic

Treatment (BEAM allogeneic transplant, ixazomib)

Carmustine DRUG

Given BEAM chemotherapy

Also known as: 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

Treatment (BEAM allogeneic transplant, ixazomib)

Cytarabine DRUG

Given BEAM chemotherapy

Also known as: .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

Treatment (BEAM allogeneic transplant, ixazomib)

Etoposide DRUG

Given BEAM chemotherapy

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16, VP 16-213, VP-16, VP-16-213, VP16

Treatment (BEAM allogeneic transplant, ixazomib)

Ixazomib Citrate DRUG

Given PO

Also known as: MLN-9708, MLN9708, Ninlaro

Treatment (BEAM allogeneic transplant, ixazomib)

Melphalan DRUG

Given BEAM chemotherapy

Also known as: 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

Treatment (BEAM allogeneic transplant, ixazomib)

Methotrexate DRUG

Given IV

Also known as: 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

Treatment (BEAM allogeneic transplant, ixazomib)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo allogeneic peripheral blood stem cell transplantation

Also known as: PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, peripheral stem cell support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

Treatment (BEAM allogeneic transplant, ixazomib)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (BEAM allogeneic transplant, ixazomib)

Tacrolimus DRUG

Given IV or PO

Also known as: FK 506, Fujimycin, Hecoria, Prograf, Protopic

Treatment (BEAM allogeneic transplant, ixazomib)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Relapsed multiple myeloma in patients that have been treated previously with autologous hematopoietic stem cell transplantation (auto-HCT), bortezomib and an immunomodulatory agent, AND with at least one of the following high-risk criteria
• High-risk multiple myeloma defined by cytogenetic or fluorescence in situ hybridization (FISH) detection of any one or more of the following:
• Deletion 17p
• Translocation t(4;14)
• Translocation t(14;16)
• Translocation t(14;20)
• Chromosome 1q gain
• Chromosome 1p deletion
• Deletion 13q by conventional karyotyping (FISH only not acceptable)
• Hypodiploidy
• High-risk gene expression profiling (GEP) at the time of relapse
• Beta-2 (B2) microglobulin \> 5.5 mg
• Plasmablastic morphology (\> 2%)
• Relapsed plasma cell leukemia
• Chemo-sensitive disease; patients with relapsed plasma cell leukemia may have received systemic therapy including an autologous transplant but it is not required; patients with relapsed multiple myeloma (MM) must have received prior systemic therapy including an autologous transplant; patient must be in at least a PR at the time of transplant; early relapse from complete response will be allowed

You may not qualify if:

• Previous allogeneic stem cell transplant
• POEMS syndrome (plasma cell dyscrasia with polyneuropathy, organomegaly, endocrinopathy, monoclonal protein \[protein\] and skin changes)
• Bilirubin \> 1.5 x the upper limit of normal
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \> 2.5 x the upper limit of normal
• Patients with \>= grade III or grade II with pain peripheral neuropathy (National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v.\] 4.03 criteria)
• Receiving steroids \> the equivalent of 10 mg prednisone daily for other medical conditions, e.g., asthma, systemic lupus erythematosus, rheumatoid arthritis
• Infection requiring systemic antibiotic therapy or other serious infection within 14 days before study enrollment
• Ongoing or active systemic infection, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive
• Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months
• Second malignancy requiring concurrent treatment or those with non-hematological malignancies (except non-melanoma skin cancers); cancer treated with curative intent \< 5 years previously will not be allowed unless approved by the protocol chair; cancer treated with curative intent \> 5 years previously is allowed
• Other serious medical or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol
• Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
• Radiotherapy within 14 days before enrollment; if the involved field is limited to a single site, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib
• Systemic treatment, within 14 days before the first dose of ixazomib, with strong inhibitors of CYP3A (clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort
• Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib including difficulty swallowing

Sponsors & Collaborators

• OHSU Knight Cancer Institute: lead
• Oregon Health and Science University: collaborator

Study Sites (2)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

OHSU Knight Cancer Institute

Portland, Oregon, 97239, United States

Location

MeSH Terms

Conditions

Leukemia, Plasma Cell; Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Stem Cell Transplantation; Carmustine; Cytarabine; Etoposide; ixazomib; Melphalan; Methotrexate; merphos; Peripheral Blood Stem Cell Transplantation; Tacrolimus

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hematopoietic Stem Cell Transplantation; Macrolides; Lactones

Study Officials

• Richard Maziarz, MD

  OHSU Knight Cancer Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 20, 2015
• First Posted: July 21, 2015
• Study Start: July 20, 2015
• Primary Completion: September 9, 2020
• Study Completion: September 9, 2020
• Last Updated: November 23, 2020

Record last verified: 2020-11

Locations

US (2)