- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01131169
Busulfan, Melphalan, Fludarabine and T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation Followed by Post Transplantation Donor Lymphocyte Infusions
A Trial of Busulfan, Melphalan, Fludarabine and T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation Followed by Post Transplantation Donor Lymphocyte Infusions for Patients With Relapsed or High-Risk Multiple Myeloma
The patients are being offered a stem cell transplant. Stem cells are very early blood cells. They have not yet matured to become red or white blood cells or platelets. They have already received the standard treatment of chemotherapy and an autologous stem cell transplant. An autologous stem cell transplant is when the patient receives their infusion of their own cells. Thi will give the patient a better chance of curing the disease, this protocol includes an infusion of stem cells from the blood (or the bone marrow) of another person. This is called an allogeneic stem cell transplant. The stem cells will begin to grow in the bone marrow and produce new blood cells.
Allogeneic stem cell transplants can cause a condition called graft-versus-host disease or GVHD. In GVHD, a kind of white blood cell from the donor (graft) begins to attack the body (host). That blood cell is called a T-cell. It is a cell that normally helps to protects against things like bacteria and viruses. In this case, the donor's T-cells see the body as foreign in the same way they would see bacteria as foreign. GVHD can be fatal. In order to lower the chance that the patient will get GVHD this protocol treatment will remove the T-cells from the donor's cells. This is called T-cell depletion. The T cells are removed by a system called "Clinimacs". This method is still being evaluated through clinical trials and not been approved by the Federal Drug Administration (FDA) at this time.
Before the transplant, the physician will treat the bone marrow to get rid of the cancer. The physician uses three chemotherapy drugs plus ATG. The chemotherapy drugs (Busulfan, Melphalan and Fludarabine) kills the cancer. ATG gets rid of any of the patients T cells that survive the chemotherapy. This ensures that the donor stem cells are not rejected. The patient will also receive additional white blood cells called lymphocytes from the donor. This is called a donor lymphocyte infusion or DLI. These additional infusions will help cause a graft-versus-myeloma effect and can help the donor stem cells grow.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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New York
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New York, New York, United States, 10065
- Memorial Sloan Kettering Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Patient must have multiple myeloma that has either relapsed or has high risk cytogenetics.
- Patients with relapsed multiple myeloma following autologous stem cell transplantation must have achieved at least partial response following additional chemotherapy (cohort 1):
- Patients are eligible if relapse occurs with complex/high-risk cytogenetics or occurs with normal cytogenetics but within 15 months following the autologous transplant.
Patients with high risk cytogenetics at diagnosis must have achieved at least very good partial response following autologous stem cell transplantation (cohort 2):
- Patients must have complex karyotype, 1q25, del17p, t4;14 and/or t14;16 by FISH and/or del13 by karyotyping.
DONOR: Patients must have a healthy HLA matched or mismatched related or unrelated donor who is willing to receive G-CSF injections and undergo apheresis for PBSC collection, or undergo a marrow harvesting procedure.
- HLA-matched related and unrelated donors Patients who have an HLA-matched related or unrelated donor are eligible for entry on this protocol. This will include a healthy donor who is genotypically matched at all A, B, C, DRB1 and DQB1 locus, loci, as tested by DNA analysis.
- HLA- mismatched related and unrelated donors Patients who do not have an HLA-matched donor but have a related or unrelated donor who have one antigen or one allele mismatch at the HLA A, B, C, DRB1 or DQB1 loci; or who have two mismatches, at HLA-DQB1 and at one other locus, will be eligible for entry on this protocol.
The following inclusion criteria are also required:
- Patients should be ≥ 21, < 73 years old.
- Patients may be of either gender or any ethnic background.
- Patients must have a Karnofsky (adult) or Performance Status ≥ 70%
- Patients must have adequate organ function measured by:
Cardiac: asymptomatic or if symptomatic then LVEF at rest must be ≥ 50% and must improve with exercise. Hepatic: < 3x ULN ALT and ≤ 1.5 total serum bilirubin, unless there is congenital benign hyperbilirubinemia.
Renal: serum creatinine <1.2 mg/dl or if serum creatinine is outside the normal range, then CrCl > 40 ml/min (measured or calculated/estimated) with dose adjustment of Fludarabine for <70ml/min.
Pulmonary: asymptomatic or if symptomatic, DLCO > 50% of predicted (corrected for hemoglobin)
- Each patient must be willing to participate as a research subject and must sign an informed consent form.
Exclusion Criteria:
- Patients achieving < Partial Response following preceding chemotherapy (cohort 1) or < Very Good Partial Response following autologous stem cell transplantation (cohort 2).
- Patients with Plasma Cell Leukemia.
- Female patients who are pregnant or breast-feeding
- Active viral, bacterial or fungal infection
- Patient seropositive for HIV-I/II; HTLV -I/II
- Patients who have undergone prior allogeneic hematopoietic stem cell transplantation.
- Patients who have had a previous malignancy that is not in remission.
- Patients with known hypersensitivity to mouse proteins (murine antibodies in ISOLEX) if receiving SBA-E- bone marrow, or chicken egg products.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: relapsed multiple myeloma
This is a two arm phase II trial to assess the progression-free and overall survival as well as the safety and efficacy of allogeneic hematopoietic stem cell transplantation using a preparative regimen with busulfan, melphalan, fludarabine, and anti-thymocyte globulin (ATG), and a T cell depleted stem cell transplant from a histocompatible related or unrelated donor in patients with relapsed or high-risk multiple myeloma.
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Patients will be cytoreduced with IV busulfan, melphalan and fludarabine.
Busulfan will be administered at a dose of 0.8mg/Kg q6hrs for 10 doses on days -9, -8, -7.
Doses for busulfan should be adjusted according to pharmacokinetic studies.
Melphalan will be administered at a dose of 70 mg/m2/day for 2 days on days -7, -6.
Fludarabine will be administered at a dose of 25 mg/m2/day for 5 days on days -6, -5, -4, -3, -2.
Patients will also receive rabbit anti-thymocyte globulin (ATG) to prevent immune mediated graft rejection.
The ATG will be administered at a dose of 2.5 mg/Kg/day IV on days -3 and -2.
Doses for busulfan, melphalan and ATG should be adjusted if patient is > 125% ideal body weight and should be calculated on adjusted ideal body weight.
Other Names:
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Experimental: high-risk multiple myeloma
This is a two arm phase II trial to assess the progression-free and overall survival as well as the safety and efficacy of allogeneic hematopoietic stem cell transplantation using a preparative regimen with busulfan, melphalan, fludarabine, and anti-thymocyte globulin (ATG), and a T cell depleted stem cell transplant from a histocompatible related or unrelated donor in patients with relapsed or high-risk multiple myeloma.
|
Patients will be cytoreduced with IV busulfan, melphalan and fludarabine.
Busulfan will be administered at a dose of 0.8mg/Kg q6hrs for 10 doses on days -9, -8, -7.
Doses for busulfan should be adjusted according to pharmacokinetic studies.
Melphalan will be administered at a dose of 70 mg/m2/day for 2 days on days -7, -6.
Fludarabine will be administered at a dose of 25 mg/m2/day for 5 days on days -6, -5, -4, -3, -2.
Patients will also receive rabbit anti-thymocyte globulin (ATG) to prevent immune mediated graft rejection.
The ATG will be administered at a dose of 2.5 mg/Kg/day IV on days -3 and -2.
Doses for busulfan, melphalan and ATG should be adjusted if patient is > 125% ideal body weight and should be calculated on adjusted ideal body weight.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Proportion of Participants With Relapsed Multiple Myeloma With Progression-free (PFS)
Time Frame: 2 years
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2 years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Proportion of Participants With Relapsed Multiple Myeloma Alive at 2 Years
Time Frame: 2 years
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2 years
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Number of Participants Who Relapse That Are Restored to Remission (CR)
Time Frame: 3 years
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To compute the current multiple myeloma free survival curve in order to account for patients who relapse and are restored to remission through DLI.
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3 years
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Collaborators and Investigators
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Antimetabolites, Antineoplastic
- Antimetabolites
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Adjuvants, Immunologic
- Lenograstim
- Melphalan
- Fludarabine
- Fludarabine phosphate
- Busulfan
- Vidarabine
Other Study ID Numbers
- 10-051 (OTHER: Fox Chase Cancer Center)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Multiple Myeloma
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Lawson Health Research InstituteThe Ottawa Hospital; Hamilton Health Sciences Corporation; Dalhousie University; Niagara Health SystemActive, not recruitingMultiple Myeloma in Relapse | Multiple Myeloma With Failed Remission | Multiple Myeloma Stage I | Multiple Myeloma Progression | Multiple Myeloma Stage II | Multiple Myeloma Stage IIICanada
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National Cancer Institute (NCI)Active, not recruitingSmoldering Multiple Myeloma | Refractory Multiple Myeloma | DS Stage I Multiple Myeloma | DS Stage II Multiple Myeloma | DS Stage III Multiple MyelomaUnited States
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Fred Hutchinson Cancer Research Center/University...National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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Case Comprehensive Cancer CenterNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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Mayo ClinicCompletedMultiple Myeloma | Stage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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National Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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City of Hope Medical CenterCompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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University of WashingtonNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
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University of Illinois at ChicagoCompletedAcute Myeloid Leukemia | Polycythemia Vera | Multiple Myeloma | Myelofibrosis | Acute Leukemia | Chronic Myelogenous Leukemia | Aplastic Anemia | Myeloproliferative Disorder | Hodgkin's Disease | Malignant Lymphoma | Lymphocytic LeukemiaUnited States
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Shanghai Jiao Tong University School of MedicineRecruitingAcute Myeloid Leukemia | Myelodysplastic SyndromesChina
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Ruijin HospitalRecruitingMyelodysplastic Syndromes | Myelodysplastic Syndrome With Excess Blasts-2 | Myelodysplastic Syndrome With Excess Blasts-1China
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Wuhan Union Hospital, ChinaRecruitingAllogeneic Hematopoietic Stem Cell Transplantation | Acute Myeloid Leukemia, Adult | Myelodysplastic Syndrome(MDS)China
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Medical College of WisconsinNational Cancer Institute (NCI); National Heart, Lung, and Blood Institute... and other collaboratorsTerminatedLeukemia, Myelocytic, AcuteUnited States
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Medical College of WisconsinNational Cancer Institute (NCI); National Heart, Lung, and Blood Institute... and other collaboratorsCompleted
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The First Affiliated Hospital of Soochow UniversityRecruitingHematopoietic Stem Cell Transplantation | Relapse/Recurrence | Hematopoietic MalignancyChina
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Vastra Gotaland RegionRecruitingStem Cell Transplantation | Acute Myeloid Leukemia (AML) in RemissionBelgium, Denmark, Finland, Hong Kong, Israel, Lithuania, Netherlands, Norway, Spain, Sweden
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Targazyme, Inc.UnknownLymphoma | Leukemia | Hodgkin's Lymphoma | Transplantation Infection | Myelodysplastic Syndrome (MDS) | Non-Hodgkin's Lymphoma (NHL) | Blood And Marrow TransplantationUnited States