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NCT00793572 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase
PHASE2
Status at capture
COMPLETED
Registry last update
2020-01-22

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Patients Surviving Progression-free

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outcome · POSTED

Number of Patients With Grade II-IV Acute GVHD

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outcome · POSTED

Number of Patients With Chronic GVHD

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outcome · POSTED

Number of Patients With Toxicities Related to Bortezomib Maintenance Therapy

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outcome · POSTED

Number of Patients With Non-relapse Mortality

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outcome · POSTED

Number of Patients Surviving Overall

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
eligibility Criteria
Inclusion Criteria: * 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 Exclusion Criteria: * 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 active non-hematological malignancies (except non-melanoma skin cancers) or those with non-hematological malignancies (except non-melanoma skin cancers) who have been rendered with no evidence of disease, but have a greater than 20% chance of having disease recurrence within 5 years; this exclusion does not apply to patients with non-hematologic malignancies that do not require therapy * 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 * Patient has an active bacterial or fungal infection unresponsive to medical therapy * DONOR: Identical twin * DONOR: Donors unwilling to donate PBSC * DONOR: Pregnancy * DONOR: Infection with HIV * DONOR: Inability to achieve adequate venous access * DONOR: Known allergy to G-CSF * DONOR: Current serious systemic illness * DONOR: Failure to meet FHCRC criteria for stem cell donation * DONOR: Age \< 12 years * DONOR: A positive anti-donor cytotoxic crossmatch * DONOR: Patient and donor pairs must not be homozygous at mismatched allele
healthy Volunteers
false
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    See Detailed Description
    intervention Names
    1. Procedure: Autologous Hematopoietic Stem Cell Transplantation
    2. Drug: Bortezomib
    3. Drug: Cyclosporine
    4. Drug: Fludarabine Phosphate
    5. Other: Laboratory Biomarker Analysis
    6. Drug: Melphalan
    7. Drug: Mycophenolate Mofetil
    8. Procedure: Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
    9. Procedure: Peripheral Blood Stem Cell Transplantation
    10. Procedure: Syngeneic Bone Marrow Transplantation
    11. Radiation: Total-Body Irradiation
    label
    Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
    description
    Undergo transplantation
    name
    Autologous Hematopoietic Stem Cell Transplantation
    other Names
    1. Autologous Stem Cell Transplantation
    type
    PROCEDURE
  2. arm Group Labels
    1. Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
    description
    Given SC
    name
    Bortezomib
    other Names
    1. [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid
    2. LDP 341
    3. MLN341
    4. PS-341
    5. PS341
    6. Velcade
    type
    DRUG
  3. arm Group Labels
    1. Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
    description
    Given IV
    name
    Cyclosporine
    other Names
    1. 27-400
    2. Ciclosporin
    3. CsA
    4. Cyclosporin
    5. Cyclosporin A
    6. Neoral
    7. OL 27-400
    8. Sandimmun
    9. Sandimmune
    10. SangCya
    type
    DRUG
  4. arm Group Labels
    1. Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
    description
    Given PO
    name
    Cyclosporine
    other Names
    1. 27-400
    2. Ciclosporin
    3. CsA
    4. Cyclosporin
    5. Cyclosporin A
    6. Neoral
    7. OL 27-400
    8. Sandimmun
    9. Sandimmune
    10. SangCya
    type
    DRUG
  5. arm Group Labels
    1. Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
    description
    Given IV
    name
    Fludarabine Phosphate
    other Names
    1. 2-F-ara-AMP
    2. 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
    3. Beneflur
    4. Fludara
    5. Oforta
    6. SH T 586
    type
    DRUG
  6. arm Group Labels
    1. Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
    description
    Correlative studies
    name
    Laboratory Biomarker Analysis
    type
    OTHER
  7. arm Group Labels
    1. Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
    description
    Given IV
    name
    Melphalan
    other Names
    1. Alanine Nitrogen Mustard
    2. CB-3025
    3. L-PAM
    4. L-Phenylalanine Mustard
    5. L-Sarcolysin
    6. L-Sarcolysin Phenylalanine mustard
    7. L-Sarcolysine
    8. Melphalanum
    9. Phenylalanine Mustard
    10. Phenylalanine Nitrogen Mustard
    11. Sarcoclorin
    12. Sarkolysin
    type
    DRUG
  8. arm Group Labels
    1. Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
    description
    Given PO
    name
    Mycophenolate Mofetil
    other Names
    1. Cellcept
    2. MMF
    type
    DRUG
  9. arm Group Labels
    1. Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
    description
    Undergo transplantation
    name
    Nonmyeloablative Allogeneic Hematopoietic Stem Cell Transplantation
    other Names
    1. Non-myeloablative allogeneic transplant
    2. Nonmyeloablative Stem Cell Transplantation
    3. NST
    type
    PROCEDURE
  10. arm Group Labels
    1. Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
    description
    Undergo transplantation
    name
    Peripheral Blood Stem Cell Transplantation
    other Names
    1. PBPC transplantation
    2. Peripheral Blood Progenitor Cell Transplantation
    3. Peripheral Stem Cell Support
    4. Peripheral Stem Cell Transplantation
    type
    PROCEDURE
  11. arm Group Labels
    1. Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
    description
    Undergo transplantation
    name
    Syngeneic Bone Marrow Transplantation
    type
    PROCEDURE
  12. arm Group Labels
    1. Tandem Auto-/Nonmyeloablative Allo-HCT and Maintenance Therapy
    description
    Undergo radiotherapy
    name
    Total-Body Irradiation
    other Names
    1. TOTAL BODY IRRADIATION
    2. Whole-Body Irradiation
    type
    RADIATION
Study design
allocation
NA
intervention Model
SINGLE_GROUP
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
32
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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.
    measure
    Number of Patients Surviving Progression-free
    time Frame
    At 2 years after the autograft
secondary Outcomes
  1. description
    Number of patients who developed acute GVHD post allogeneic transplant. aGVHD Stages Skin: 1. \- a maculopapular eruption involving \< 25% BSA 2. \- a maculopapular eruption involving 25 - 50% BSA 3. \- generalized erythroderma 4. \- generalized erythroderma w/ bullous formation and often w/ desquamation Liver: 1. \- bilirubin 2.0 - 3.0 mg/100 mL 2. \- bilirubin 3 - 5.9 mg/100 mL 3. \- bilirubin 6 - 14.9 mg/100 mL 4. \- bilirubin \> 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade II: Stage 1 - 2 skin w/ no gut/liver involvement Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 w/ extreme constitutional symptoms or death
    measure
    Number of Patients With Grade II-IV Acute GVHD
    time Frame
    100 days post allo transplant
  2. description
    Number of subjects with classic chronic or chronic extensive GVHD post allogeneic transplant.
    measure
    Number of Patients With Chronic GVHD
    time Frame
    1 year post allo
  3. description
    Number of subjects with toxicities related to bortezomib maintenance therapy post-transplant.
    measure
    Number of Patients With Toxicities Related to Bortezomib Maintenance Therapy
    time Frame
    Up to 100 days after the autograft or allograft
  4. description
    Number of subjects with non-relapse mortalities post allogeneic transplant.
    measure
    Number of Patients With Non-relapse Mortality
    time Frame
    200 and 365 days after allo
  5. description
    Number of subjects surviving two years post autologous transplant.
    measure
    Number of Patients Surviving Overall
    time Frame
    At 2 years after the autograft
Full study description
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.
detailed Description
PRIMARY OBJECTIVES: I. Progression-free survival (PFS) at 2 years after the autograft (=\< 50% in historic controls). SECONDARY OBJECTIVES: I. Overall survival (OS) at 2 years after the autograft. II. Non-relapse mortality (NRM) at 200 days and 1 year after allograft. III. Incidence of grades II-IV acute graft-versus-host-disease (GVHD) and chronic extensive GVHD. IV. Safety of bortezomib maintenance therapy after stem cell transplantation. OUTLINE: PERIPHERAL BLOOD STEM CELL (PBSC) MOBILIZATION: Patients undergo PBSC mobilization and collection using the preferred regimens at the participating institution. CONDITIONING CHEMOTHERAPY AND AUTOLOGOUS OR SYNGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT): Patients receive high-dose melphalan intravenously (IV) on day -2 followed by an autologous or syngeneic HSCT on day 0. NON-MYELOABLATIVE ALLOGENEIC HSCT: Beginning 40-180 days after autologous HSCT, patients receive 1 of the following regimens: 1. HLA-IDENTICAL RELATED DONOR: Patients receive cyclosporine IV or orally (PO) twice daily (BID) starting on days -3 to 56, and taper until day 180. Patients then undergo total-body irradiation (TBI) and non-myeloablative allogeneic HSCT on day 0. Four to six hours after completion of allogeneic HSCT, patients receive mycophenolate mofetil (MMF) PO BID on days 0-27. 2. HLA-UNRELATED DONOR: Patients receive fludarabine phosphate IV on days -4 to -2. Patients also receive cyclosporine IV or PO BID starting on days -3 to 100 and taper until day 180. Patients then undergo TBI and non-myeloablative allogeneic HSCT on day 0. Four to six hours after completion of allogeneic HSCT, patients receive MMF PO thrice daily (TID) on days 0-27 and then BID on days 27-40 with taper of MMF on days 40-96. MAINTENANCE THERAPY: Beginning 60-120 days after allogeneic HSCT, patients receive bortezomib subcutaneously (SC) on days 1 and 4 of 14-day cycles for 9 months or for up to 18 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year and then annually for up to 5 years.
Source references
references
  1. citation
    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
    32499241
    type
    DERIVED
  2. citation
    Green 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
    29296873
    type
    DERIVED
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