- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00899847
Phase 2 Study of Autologous Followed by Nonmyeloablative Allogeneic Transplantation Using TLI & ATG
A Phase 2 Study of Autologous Followed by Nonmyeloablative Allogeneic Transplantation Using Total Lymphoid Irradiation (TLI) and Antithymocyte Globulin (ATG) in Multiple Myeloma Patients
Study Overview
Status
Conditions
Intervention / Treatment
- Procedure: Autologous peripheral blood stem cells (auto-PBSC) transplantation
- Procedure: Allogeneic peripheral blood stem cells (allo-PBSC) transplantation
- Drug: Filgrastim
- Drug: Cyclophosphamide
- Drug: Melphalan
- Drug: Cyclosporine
- Radiation: Total lymphoid irradiation
- Biological: Rabbit anti-thymocyte globulin
- Drug: Mycophenolate Mofetil 250mg
- Drug: Solumedrol
- Drug: Diphenhydramine
- Drug: Acetaminophen
- Drug: Hydrocortisone
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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California
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Stanford, California, United States, 94305
- Stanford University School of Medicine
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
PARTICIPANT INCLUSION CRITERIA
- Stage II-III multiple myeloma or have progression after initial treatment of Stage I disease (Durie Salmon Staging). Patients with plasma cell leukemia are also included.
- Multiple myeloma / plasma cell leukemia diagnosis confirmed by pathology reviewed at Stanford University Medical Center.
- 18 to ≤ 75 years of age
- Karnofsky Performance Status > 70%.
- Corrected Carbon monoxide diffusing capacity (Dlco) > 60%
- Left ventricle ejection fraction (LVEF) > 50%.
- Alanine aminotransferase (ALT) ≤ 2 x normal
- Aspartate aminotransferase (AST) ≤ 2 x normal
- Total bilirubin ≤ 2 mg/dL, unless hemolysis or Gilbert's disease.
- Estimated creatinine clearance > 50 mL/min.
- Identified related or unrelated Human leukocyte antigen (HLA)-identical donor or donor with one antigen/allele mismatch in (HLA-A, B, C or DRB1).
- Signed informed consent.
DONOR INCLUSION CRITERIA
- At least 17 years of age
- HIV-seronegative
- Must be capable of giving signed, informed consent
- No contraindication to the administration of filgrastim
- Willing to have a central venous catheter placed for apheresis if peripheral veins are inadequate
PARTICIPANT EXCLUSION CRITERIA
- Prior allogeneic hematopoietic cell transplantation
- Uncontrolled active infection
- Uncontrolled congestive heart failure or angina
- HIV-positive
- Pregnant or nursing
DONOR EXCLUSION CRITERIA
- Serious medical or psychological illness
- Pregnant or lactating
- Prior malignancies within the last 5 years except for non-melanoma skin cancers
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Autologous-Allogeneic Peripheral Blood Stem Cell Transplant
Study treatment is a high-dose sequential chemotherapy approach to hematopoietic stem cell (HSC) transplant that uses an autologous peripheral blood stem cell (auto-PBSC) transplant followed by allogeneic peripheral blood stem cell (allo-PBSC) transplant to evaluate improved graft vs host disease (GvHD) control.
Participant auto-PBSC are mobilized with cyclophosphamide (also to provide cytoreduction) and filgrastim, followed by melphalan as an auto-PBSC conditioning agent, then auto-PBSC infusion.
For the allo-PBSC transplant, donors are mobilized with filgrastim, and participants receive a regimen of total lymphoid irradiation and anti-thymocyte globulin (TLI/ATG), followed by infusion of donor allo-PBSC.
Solumedrol, diphenhydramine, acetaminophen, and hydrocortisone are administered as premedications, and rabbit anti-thymocyte globulin (ATG) plus mycophenolate mofetil (MMF) are administered for post-allo-PBSC immunosuppression.
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Auto-PBSC ≥ 2 to 3 x 10e6 CD34+ cells/kg are intravenously (IV) infused as part of the combination stem cell therapy. and allogeneic stem cells are administered intravenous (IV) infusion to reestablish hematopoietic function in patients whose bone marrow or immune system is damaged or defective
Other Names:
Allo-PBSC (target collection ≥ 5 x 10e6 CD34+ cells/kg) are intravenously (IV) infused as part of the combination stem cell therapy.
Other Names:
Filgrastim is administered subcutaneously (SC) at 10 µg/kg/day for auto-PBSC mobilization starting day 2 of mobilization until the last day of apheresis. Filgrastim is administered SC at 5 µg/kg/day from Day 6 after auto-PBSC infusion to hematologic recovery. Filgrastim is administered SC at 16 µg/kg/day for donor allo-PBSC mobilization at from Day - 4 to Day 0, prior to allo-PBSC collection.
Other Names:
Cyclophosphamide is administered intravenously (IV) at 4 g/m2 on Day 1 of the auto-PBSC mobilization regimen.
Other Names:
Melphalan is administered after CSP at 200 mg/m2 intravenously (IV) on Day -2 before auto-PBSC infusion.
Other Names:
Cyclosporine is administered by mouth (PO) for allo-PBSC graft vs host disease (GvHD) prophylaxis at 5 mg/kg from Day -3 through Bay +56.
Tacrolimus may substituted.
Other Names:
Total lymphoid irradiation is administered at 80 centigrey (cGy) on Day -11 to -7; and Day -4 to -2 before alllo-PBSC infusion.
TLI is also administered at 80 centigrey (cGy) x 2 on Day -1 before alllo-PBSC infusion.
Other Names:
ATG 1.5 mg/kg is administered intravenously (IV) on Day -11 to -7 before allo-PBSC infusion.
Other Names:
MMF is administered at 15 mg/kg 3x/day by mouth (PO) after allo-PBSC through Day 40, followed by 10% dose reduction weekly (dose taper) through day 96, and adjusted if there is evidence of MMF-related GI toxicity or excessive myelosuppression
Other Names:
Solumedrol 1 mg/kg is administered intravenously (IV) on Day -11 to -7 as a premedication for ATG and allo-PBSC infusion
Other Names:
Diphenhydramine 25 to 50 mg is administered as a premedication for the ATG; allo-PBSC; and DLI infusions.
Other Names:
Acetaminophen 650 mg is administered as a premedication for the ATG and allo-PBSC infusions.
Other Names:
Hydrocortisone 100 mg is administered intravenously (IV) is a premedication for the allo-PBSC and DLI infusions.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of Graft Versus Host Disease (GvHD)
Time Frame: 2 years after the last participant is enrolled.
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To evaluate the incidence acute GvHD of this tandem autologous/allogeneic transplant setting
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2 years after the last participant is enrolled.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Median Time to Engraftment After Auto-PBSC Transplant
Time Frame: 1 month
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Engraftment is assessed as:
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1 month
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Median Time to Engraftment After Allo-PBSC Transplant
Time Frame: 1 month
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Engraftment is assessed as:
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1 month
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Overall Response Rate (ORR)
Time Frame: 1 year
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Overall response rate (ORR) = Complete Response Rate (CRR) + Partial Response Rate (PRR)
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1 year
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Complete Response Rate (CRR)
Time Frame: 1 year
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Complete response rate (CRR) was assessed as all of:
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1 year
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Partial Response Rate (PRR)
Time Frame: 1 year
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Partial response rate (PRR) was assessed as
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1 year
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Event-free Survival (EFS)
Time Frame: 2 years after the last participant is enrolled
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To evaluate the graft versus myeloma effect by monitoring rate of event-free survival (EFS)
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2 years after the last participant is enrolled
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Overall Survival (OS)
Time Frame: 2 years after the last participant is enrolled
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To evaluate the graft versus myeloma effect by monitoring rate of overall survival (OS)
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2 years after the last participant is enrolled
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
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
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Central Nervous System Depressants
- Autonomic Agents
- Peripheral Nervous System Agents
- Enzyme Inhibitors
- Analgesics
- Sensory System Agents
- Anesthetics
- Analgesics, Non-Narcotic
- Anti-Inflammatory Agents
- Antirheumatic Agents
- Antipyretics
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Neuroprotective Agents
- Protective Agents
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Dermatologic Agents
- Anti-Bacterial Agents
- Hypnotics and Sedatives
- Adjuvants, Immunologic
- Anesthetics, Local
- Antibiotics, Antineoplastic
- Antifungal Agents
- Anti-Allergic Agents
- Antitubercular Agents
- Sleep Aids, Pharmaceutical
- Histamine H1 Antagonists
- Histamine Antagonists
- Histamine Agents
- Antipruritics
- Antibiotics, Antitubercular
- Calcineurin Inhibitors
- Methylprednisolone Hemisuccinate
- Cyclophosphamide
- Lenograstim
- Acetaminophen
- Diphenhydramine
- Promethazine
- Melphalan
- Mycophenolic Acid
- Hydrocortisone
- Thymoglobulin
- Antilymphocyte Serum
- Cyclosporine
- Cyclosporins
- Mechlorethamine
Other Study ID Numbers
- IRB-15772
- SU-04142009-2259 (Other Identifier: Stanford University)
- BMT201 (Other Identifier: OnCore Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
product manufactured in and exported from the U.S.
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.
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