Autologous or Syngeneic Stem Cell Transplant Followed by Donor Stem Cell Transplant and Bortezomib in Treating Patients With Newly Diagnosed High-Risk, Relapsed, or Refractory Multiple Myeloma
Tandem Autologous HCT/Nonmyeloablative Allogeneic HCT From HLA-Matched Related and Unrelated Donors Followed by Bortezomib Maintenance Therapy for Patients With High-Risk Multiple Myeloma
4 other identifiers
interventional
32
1 country
1
Brief Summary
This phase II trial studies the side-effects and anti-cancer effects of giving an autologous or syngeneic stem cell transplant followed by an allogeneic donor stem cell transplant and bortezomib. Patients treated on this trial have newly diagnosed high-risk, relapsed, or refractory multiple myeloma (MM). Giving chemotherapy before an autologous stem cell transplant slows or stops the growth of cancer cells by preventing them from dividing or killing them. Stem cells that were harvested earlier from the patient's blood and frozen are then returned to the patient to replace the blood-forming cells that were destroyed by chemotherapy. Giving chemotherapy and total-body irradiation before an allogeneic donor stem cell transplant also prevents the patient's immune system from rejecting the donor's stem cells. Undergoing an autologous or syngeneic stem cell transplantation followed by an allogeneic donor stem cell transplant and bortezomib may be overall more effective in killing cancer cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Oct 2008
Longer than P75 for phase_2
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 1, 2008
CompletedFirst Submitted
Initial submission to the registry
November 18, 2008
CompletedFirst Posted
Study publicly available on registry
November 19, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2016
CompletedResults Posted
Study results publicly available
May 18, 2017
CompletedJanuary 22, 2020
January 1, 2020
8 years
November 18, 2008
April 11, 2017
January 13, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
Number of Patients Surviving Progression-free
Number of subjects surviving without progressive disease post-transplant. Progressive disease criteria: 1. Greater than 25% increase in serum (absolute increase must be ≥0.5 g/dL) or urine (absolute increase must be ≥200 mg/24h) M proteins compared to best response status after autologous transplant. 2. Appearance of new lytic bone lesions or plasmacytomas.
At 2 years after the autograft
Secondary Outcomes (5)
Number of Patients With Grade II-IV Acute GVHD
100 days post allo transplant
Number of Patients With Chronic GVHD
1 year post allo
Number of Patients With Toxicities Related to Bortezomib Maintenance Therapy
Up to 100 days after the autograft or allograft
Number of Patients With Non-relapse Mortality
200 and 365 days after allo
Number of Patients Surviving Overall
At 2 years after the autograft
Study Arms (1)
Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
EXPERIMENTALSee Detailed Description
Interventions
Undergo transplantation
Given SC
Given IV
Given IV
Correlative studies
Given IV
Given PO
Undergo transplantation
Undergo transplantation
Undergo transplantation
Undergo radiotherapy
Eligibility Criteria
You may qualify if:
- Newly diagnosed patients must have received induction therapy (e.g., vincristine, doxorubicin, dexamethasone \[VAD\], thalidomide/dexamethasone) for a minimum of 4 cycles
- Must have the capacity to give informed consent
- Must have an human leukocyte antigen (HLA) genotypically identical sibling or a phenotypically matched relative or, at a minimum, a high likelihood of identifying an HLA-matched unrelated donor; the determination of availability of a suitable unrelated donor may be based on a World-Book search
- In addition, patients must meet at least one of the criteria A-I (A-G at time of diagnosis or pre-autograft):
- A) Any abnormal karyotype by metaphase analysis except for isolated t(11,14) and constitutional cytogenetic abnormality
- B) Fluorescence in situ hybridization (FISH) translocation 4;14
- C) FISH translocation 14;16
- D) FISH deletion 17p
- E) Beta2-microglobulin \> 5.5 mg/L
- F) Cytogenetic hypodiploidy
- G) Plasmablastic morphology (\>= 2%)
- DONOR: HLA genotypically identical sibling or phenotypically matched relative OR
- DONOR: HLA phenotypically matched unrelated donor (according to Standard Practice HLA matching criteria, Grade #2.1)
- Matched HLA-A, B, C, DRB1, and DQB1 alleles by high resolution typing.
- Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing
You may not qualify if:
- Recurrent or non-responsive (less than partial response \[PR\]) MM after at least two different lines of conventional chemotherapy
- Progressive MM after a previous autograft
- Life expectancy severely limited by disease other than malignancy
- Seropositive for the human immunodeficiency virus (HIV)
- Females who are pregnant or breastfeeding
- Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
- Patients with fungal infection and radiological progression after receipt of amphotericin B or active triazole for greater than 1 month
- Patients with the following organ dysfunction:
- Symptomatic coronary artery disease or ejection fraction \< 40% or other cardiac failure requiring therapy; myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
- Ejection fraction is required if the patient has a history of anthracyclines or history of cardiac disease
- Diffusing lung capacity for carbon monoxide (DLCO) \< 50%, forced expiratory volume in 1 second (FEV) \< 50% and/or receiving supplementary continuous oxygen; the Fred Hutchinson Cancer Research Center (FHCRC) principle investigator (PI) of the study must approve of enrollment of all patients with pulmonary nodules
- Liver function abnormalities: Patient with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; the patient will be excluded if he/she is found to have fulminant liver failure; cirrhosis of the liver with evidence of portal hypertension; alcoholic hepatitis; esophageal varices; a history of bleeding esophageal varices; hepatic encephalopathy; uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time ascites related to portal hypertension; bacterial or fungal liver abscess; biliary obstruction; chronic viral hepatitis with total serum bilirubin \> 3 mg/dL; and symptomatic biliary disease;
- Karnofsky score \< 70% for adult patients
- Patient with poorly controlled hypertension and on multiple antihypertensives
- Patients with current \>= grade 2 peripheral neuropathy
- +12 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Fred Hutchinson Cancer Centerlead
- Millennium Pharmaceuticals, Inc.collaborator
- National Cancer Institute (NCI)collaborator
Study Sites (1)
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
Related Publications (2)
Cooper JP, Storer BE, Granot N, Gyurkocza B, Sorror ML, Chauncey TR, Shizuru J, Franke GN, Maris MB, Boyer M, Bruno B, Sahebi F, Langston AA, Hari P, Agura ED, Lykke Petersen S, Maziarz RT, Bethge W, Asch J, Gutman JA, Olesen G, Yeager AM, Hubel K, Hogan WJ, Maloney DG, Mielcarek M, Martin PJ, Flowers MED, Georges GE, Woolfrey AE, Deeg JH, Scott BL, McDonald GB, Storb R, Sandmaier BM. Allogeneic hematopoietic cell transplantation with non-myeloablative conditioning for patients with hematologic malignancies: Improved outcomes over two decades. Haematologica. 2021 Jun 1;106(6):1599-1607. doi: 10.3324/haematol.2020.248187.
PMID: 32499241DERIVEDGreen DJ, Maloney DG, Storer BE, Sandmaier BM, Holmberg LA, Becker PS, Fang M, Martin PJ, Georges GE, Bouvier ME, Storb R, Mielcarek M. Tandem autologous/allogeneic hematopoietic cell transplantation with bortezomib maintenance therapy for high-risk myeloma. Blood Adv. 2017 Nov 9;1(24):2247-2256. doi: 10.1182/bloodadvances.2017010686. eCollection 2017 Nov 14.
PMID: 29296873DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Dr. Marco Mielcarek
- Organization
- Fred Hutchinson Cancer Research Center
Study Officials
- PRINCIPAL INVESTIGATOR
Marco Mielcarek
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- 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
November 18, 2008
First Posted
November 19, 2008
Study Start
October 1, 2008
Primary Completion
October 1, 2016
Study Completion
October 1, 2016
Last Updated
January 22, 2020
Results First Posted
May 18, 2017
Record last verified: 2020-01