Ignite Creation Date:
2025-12-24 @ 2:25 PM
Ignite Modification Date:
2026-02-24 @ 12:13 AM
Study NCT ID:
NCT00995059
Status:
WITHDRAWN
Last Update Posted:
2023-01-05
First Post:
2009-10-12
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Bortezomib Before Donor Stem Cell Transplant in Treating Patients With Multiple Myeloma
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'removedCountries': ['United States']}, 'conditionBrowseModule': {'meshes': [{'id': 'D009101', 'term': 'Multiple Myeloma'}], 'ancestors': [{'id': 'D054219', 'term': 'Neoplasms, Plasma Cell'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D020141', 'term': 'Hemostatic Disorders'}, {'id': 'D014652', 'term': 'Vascular Diseases'}, {'id': 'D002318', 'term': 'Cardiovascular Diseases'}, {'id': 'D010265', 'term': 'Paraproteinemias'}, {'id': 'D001796', 'term': 'Blood Protein Disorders'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D006474', 'term': 'Hemorrhagic Disorders'}, {'id': 'D008232', 'term': 'Lymphoproliferative Disorders'}, {'id': 'D007160', 'term': 'Immunoproliferative Disorders'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D014180', 'term': 'Transplantation'}, {'id': 'D000069286', 'term': 'Bortezomib'}, {'id': 'D008558', 'term': 'Melphalan'}, {'id': 'D000961', 'term': 'Antilymphocyte Serum'}, {'id': 'C512542', 'term': 'thymoglobulin'}, {'id': 'D020123', 'term': 'Sirolimus'}, {'id': 'D016559', 'term': 'Tacrolimus'}, {'id': 'D014916', 'term': 'Whole-Body Irradiation'}], 'ancestors': [{'id': 'D013514', 'term': 'Surgical Procedures, Operative'}, {'id': 'D001897', 'term': 'Boronic Acids'}, {'id': 'D000148', 'term': 'Acids, Noncarboxylic'}, {'id': 'D000143', 'term': 'Acids'}, {'id': 'D007287', 'term': 'Inorganic Chemicals'}, {'id': 'D001896', 'term': 'Boron Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D011719', 'term': 'Pyrazines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D009588', 'term': 'Nitrogen Mustard Compounds'}, {'id': 'D009150', 'term': 'Mustard Compounds'}, {'id': 'D006846', 'term': 'Hydrocarbons, Halogenated'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D010649', 'term': 'Phenylalanine'}, {'id': 'D024322', 'term': 'Amino Acids, Aromatic'}, {'id': 'D000598', 'term': 'Amino Acids, Cyclic'}, {'id': 'D000596', 'term': 'Amino Acids'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D007106', 'term': 'Immune Sera'}, {'id': 'D000906', 'term': 'Antibodies'}, {'id': 'D007136', 'term': 'Immunoglobulins'}, {'id': 'D007162', 'term': 'Immunoproteins'}, {'id': 'D001798', 'term': 'Blood Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D012712', 'term': 'Serum Globulins'}, {'id': 'D005916', 'term': 'Globulins'}, {'id': 'D001688', 'term': 'Biological Products'}, {'id': 'D045424', 'term': 'Complex Mixtures'}, {'id': 'D018942', 'term': 'Macrolides'}, {'id': 'D007783', 'term': 'Lactones'}, {'id': 'D011878', 'term': 'Radiotherapy'}, {'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D008919', 'term': 'Investigative Techniques'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1', 'PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 0}}, 'statusModule': {'overallStatus': 'WITHDRAWN', 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2011-02', 'lastUpdateSubmitDate': '2023-01-04', 'studyFirstSubmitDate': '2009-10-12', 'studyFirstSubmitQcDate': '2009-10-13', 'lastUpdatePostDateStruct': {'date': '2023-01-05', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2009-10-14', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Tolerability as assessed by CTCAE v3.0 (Phase I)'}, {'measure': 'Assessment of toxicity (Phase I)'}, {'measure': 'Proportion of successes'}, {'measure': 'Transplant-related mortality (TRM) (Phase II)', 'timeFrame': '100 days'}, {'measure': 'Rate acute graft-vs-host disease (GVHD) (Phase I)'}], 'secondaryOutcomes': [{'measure': 'Rate of grades II-IV and grades III-IV acute graft-vs-host disease (GVHD)'}, {'measure': 'Cumulative rate of chronic GVHD'}, {'measure': 'Overall response'}, {'measure': 'Overall survival'}, {'measure': 'Progression-free survival'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['stage I multiple myeloma', 'stage II multiple myeloma', 'stage III multiple myeloma'], 'conditions': ['Multiple Myeloma', 'Refractory Multiple Myeloma']}, 'descriptionModule': {'briefSummary': "Rationale: Giving bortezomib and low doses of chemotherapy and total-body irradiation before a donor stem cell transplant or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving sirolimus and tacrolimus before and after transplant may stop this from happening.\n\nPurpose: This phase I/II trial is studying the side effects and best dose of bortezomib before donor stem cell transplant in treating patients with multiple myeloma.", 'detailedDescription': 'Objectives:\n\nI. To determine the maximum tolerated dose (MTD) of bortezomib when used in a novel conditioning regimen for patients undergoing allogeneic stem cell transplantation for multiple myeloma.\n\nII. To evaluate the tolerability and feasibility of this novel conditioning regimen and GVHD prophylaxis strategy incorporating several anti-myeloma agents, including bortezomib, in patients undergoing allogeneic stem cell transplantation for multiple myeloma.\n\nIII. To obtain an initial assessment of the efficacy of this novel conditioning regimen.\n\nOutline: This is a phase I dose-escalation study of bortezomib followed by a phase II study.\n\nReduced-Intensity Conditioning: Patients receive bortezomib IV and then undergo fractionated total-body irradiation on days -5 and -2. Patients receive thymoglobulin IV over 6 hours on days -5 to -2 and melphalan IV over 30 minutes on days -4 to -3.\n\nAllogenic Stem Cell Transplantation: Patients undergo bone marrow or peripheral blood stem cell transplant on day 0.\n\nGraft versus Host Disease Prophylaxis: Beginning on day -3, patients receive oral sirolimus and taper beginning on day 61. Beginning on day -2, patients receive oral or IV tacrolimus and taper beginning on day 101. After completion of the study treatment, patients are followed every 3 months.'}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* ECOG performance status (PS) 0, 1, or 2\n* Diagnosis of symptomatic multiple myeloma\n* High risk myeloma as defined by progressive disease =\\< 12 months after high dose chemotherapy and autologous HSC transplant or presences of poor prognostic features such as deletion of chromosome 13 or hypodiploidy by standard cytogenetics, or t(4; 14) by fluorescence in situ hybridization (FISH), or t(14;16) by FISH, or 17p- by FISH, or plasma cell labeling index \\>= 3%\n* Availability of a HLA fully-matched or 1 mismatch related donor by low-resolution HLA typing for the loci A, B, C, DRB1 and DQB1 or HLA fully-matched unrelated donor by high-resolution typing for loci A, B, C and DRB1 and at least low-resolution for loci DQB1\n* Recovery from toxicity of previous chemotherapy (excludes grade 1 neurotoxicity and hematological toxicity)\n* Physically and psychologically capable of undergoing bone marrow or PBSC transplant\n* Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care\n* Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control for the during of the study\n* Male subject agrees to use an acceptable method for contraception for the duration of the study\n\nExclusion Criteria:\n\n* Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV hear failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities\n* NOTE: Prior to study entry, and ECG abnormality at screening has to be documented by the investigator as not medically relevant\n* Significant cardiac dysfunction defined as left ventricle ejection fraction \\< 40% or presence of symptomatic coronary artery disease\n* Significant pulmonary disease defined as FEV \\< 50% or CLCO \\< 50% of the predicted values\n* Pre existing peripheral neuropathy grade \\> 1\n* Significant renal dysfunction defined as estimated creatinine clearance \\< 50 ml/min\n* Significant liver dysfunction defined as total bilirubin \\>= 2 x upper limit of normal (ULN) or AST, ALT \\>= 3 x ULN\n* Seroreactive for HIV, HTLV I or II, HBV, HCV\n* Presence of uncontrolled bacterial, viral, or fungal infection\n* Known allergy to any of the component of the investigational treatment regimen or required ancillary treatments\n* Considered unable to tolerate the included doses of total body irradiation due to previous treatment with radiation\n* Female subject is pregnant or breast-feeding\n* Other active concurrent malignancy\n* Prior allogeneic bone marrow/peripheral blood stem cell transplant\n* Received other investigational drugs =\\< 14 days prior to enrollment'}, 'identificationModule': {'nctId': 'NCT00995059', 'briefTitle': 'Bortezomib Before Donor Stem Cell Transplant in Treating Patients With Multiple Myeloma', 'organization': {'class': 'OTHER', 'fullName': 'Mayo Clinic'}, 'officialTitle': 'A Phase I/II Study of a Novel Reduced Intensity Conditioning Regimen for Allogeneic Stem Cell Transplantation in Patients With Multiple Myeloma', 'orgStudyIdInfo': {'id': 'MC078F'}, 'secondaryIdInfos': [{'id': 'NCI-2009-01249', 'type': 'REGISTRY', 'domain': 'NCI-CTRP'}, {'id': '08-003029', 'type': 'OTHER', 'domain': 'Mayo Clinic IRB'}, {'id': 'MC078F', 'type': 'OTHER', 'domain': 'Mayo Clinic Cancer Center'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Arm 1', 'description': 'CONDITIONING: Patients receive bortezomib IV and then undergo fractionated total-body irradiation on days -5 and -2. Patients receive thymoglobulin IV over 6 hours on days -5 to -2 and melphalan IV over 30 minutes on days -4 to -3. ALLOGENEIC STEM CELL TRANSPLANTATION: Patients undergo bone marrow or peripheral blood stem cell transplant on day 0. GRAFT-VS-HOST DISEASE PROPHYLAXIS: Beginning on day -3, patients receive oral sirolimus and taper beginning on day 61. Beginning on day -2, patients receive oral or IV tacrolimus and taper beginning on day 101.', 'interventionNames': ['Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation', 'Procedure: allogeneic bone marrow transplantation', 'Drug: bortezomib', 'Drug: melphalan', 'Drug: anti-thymocyte globulin', 'Drug: sirolimus', 'Drug: tacrolimus', 'Radiation: total-body irradiation']}], 'interventions': [{'name': 'nonmyeloablative allogeneic hematopoietic stem cell transplantation', 'type': 'PROCEDURE', 'description': 'Undergo transplantation', 'armGroupLabels': ['Arm 1']}, {'name': 'allogeneic bone marrow transplantation', 'type': 'PROCEDURE', 'otherNames': ['bone marrow therapy, allogeneic', 'bone marrow therapy, allogenic', 'transplantation, allogeneic bone marrow', 'transplantation, allogenic bone marrow'], 'description': 'Undergo transplantation', 'armGroupLabels': ['Arm 1']}, {'name': 'bortezomib', 'type': 'DRUG', 'otherNames': ['LDP 341', 'MLN341', 'PS-341', 'VELCADE'], 'description': 'Given IV', 'armGroupLabels': ['Arm 1']}, {'name': 'melphalan', 'type': 'DRUG', 'otherNames': ['Alkeran', 'CB-3025', 'L-PAM', 'L-phenylalanine mustard', 'L-Sarcolysin', 'Melfalan'], 'description': 'Given IV', 'armGroupLabels': ['Arm 1']}, {'name': 'anti-thymocyte globulin', 'type': 'DRUG', 'otherNames': ['ATG', 'ATGAM', 'lymphocyte immune globulin', 'Thymoglobulin'], 'description': 'Given IV', 'armGroupLabels': ['Arm 1']}, {'name': 'sirolimus', 'type': 'DRUG', 'otherNames': ['AY 22989', 'RAPA', 'Rapamune', 'rapamycin', 'SILA 9268A', 'SLM'], 'description': 'Given orally', 'armGroupLabels': ['Arm 1']}, {'name': 'tacrolimus', 'type': 'DRUG', 'otherNames': ['Advagraf', 'FK 506', 'Prograf', 'Protopic'], 'description': 'Given oral or IV', 'armGroupLabels': ['Arm 1']}, {'name': 'total-body irradiation', 'type': 'RADIATION', 'otherNames': ['TBI'], 'description': 'Undergo total-body irradiation', 'armGroupLabels': ['Arm 1']}]}, 'contactsLocationsModule': {'overallOfficials': [{'name': 'Martha Q. Lacy, M.D.', 'role': 'STUDY_CHAIR', 'affiliation': 'Mayo Clinic'}, {'name': 'James L. Slack, M.D.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Mayo Clinic'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Mayo Clinic', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}