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Phase 2 Study of Autologous Followed by Nonmyeloablative Allogeneic Transplantation Using TLI & ATG

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00899847
First Posted: May 12, 2009
Last Update Posted: October 20, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Wen-Kai Weng, Stanford University
  Purpose
To evaluate the toxicity and tolerability of this tandem autologous/allogeneic transplant approach for patients with advanced stage multiple myeloma.

Condition Intervention Phase
Transplantation, Homologous Transplantation, Autologous Multiple Myeloma Blood and Marrow Transplant (BMT) 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 Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Autologous Followed by Nonmyeloablative Allogeneic Transplantation Using Total Lymphoid Irradiation (TLI) and Antithymocyte Globulin (ATG) in Multiple Myeloma Patients

Resource links provided by NLM:


Further study details as provided by Wen-Kai Weng, Stanford University:

Primary Outcome Measures:
  • Incidence of Graft Versus Host Disease (GvHD) [ Time Frame: 2 years after the last participant is enrolled. ]
    To evaluate the incidence acute GvHD of this tandem autologous/allogeneic transplant setting


Secondary Outcome Measures:
  • Median Time to Engraftment After Auto-PBSC Transplant [ Time Frame: 1 month ]

    Engraftment is assessed as:

    • Neutrophil engraftment is > 0.5 x 10⁹/L after cytopenia
    • Platelet engraftment is > 20 x 10⁹/L after cytopenia

  • Median Time to Engraftment After Allo-PBSC Transplant [ Time Frame: 1 month ]

    Engraftment is assessed as:

    • Neutrophil engraftment is > 0.5 x 10⁹/L after cytopenia
    • Platelet engraftment is > 20 x 10⁹/L after cytopenia

  • Overall Response Rate (ORR) [ Time Frame: 1 year ]
    Overall response rate (ORR) = Complete Response Rate (CRR) + Partial Response Rate (PRR)

  • Complete Response Rate (CRR) [ Time Frame: 1 year ]

    Complete response rate (CRR) was assessed as all of:

    • Negative immunoflixation on the serum and urine
    • Disappearance of any soft tissue plasmacytomas
    • < 5% plasma cells in bone marrow

  • Partial Response Rate (PRR) [ Time Frame: 1 year ]

    Partial response rate (PRR) was assessed as

    • > 50% reduction in serum M-protein plus urine M-protein reduction by 90% or < 200 mg/24 hr
    • If serum M-protein is not measurable, then > 50% reduction in the involved serum free light chain
    • If involved serum free light chain is not measurable, then > 50% reduction in the bone marrow plasma cell percentage + > 50% reduction in the size of any soft tissue plasmacytoma.

  • Event-free Survival (EFS) [ Time Frame: 2 years after the last participant is enrolled ]
    To evaluate the graft versus myeloma effect by monitoring rate of event-free survival (EFS)

  • Overall Survival (OS) [ Time Frame: 2 years after the last participant is enrolled ]
    To evaluate the graft versus myeloma effect by monitoring rate of overall survival (OS)


Enrollment: 9
Study Start Date: May 2009
Study Completion Date: December 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Procedure: Autologous peripheral blood stem cells (auto-PBSC) transplantation

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:
  • auto-PBPC
  • Autologous peripheral blood progenitor cells (auto-PBPC) transplantation
Procedure: Allogeneic peripheral blood stem cells (allo-PBSC) transplantation
Allo-PBSC (target collection ≥ 5 x 10e6 CD34+ cells/kg) are intravenously (IV) infused as part of the combination stem cell therapy.
Other Names:
  • allo-PBSC
  • Allogeneic peripheral blood progenitor cells (allo-PBPC) transplantation
Drug: Filgrastim

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:
  • Neupogen
  • Granulocyte colony-stimulating factor (G-CSF)
  • r-metHuG-CSF
Drug: Cyclophosphamide
Cyclophosphamide is administered intravenously (IV) at 4 g/m2 on Day 1 of the auto-PBSC mobilization regimen.
Other Names:
  • Ciclofosfamida
  • Ciclofosfamide
  • Claphene
  • CP monohydrate (CPM)
  • CSP
Drug: Melphalan
Melphalan is administered after CSP at 200 mg/m2 intravenously (IV) on Day -2 before auto-PBSC infusion.
Other Names:
  • L-Sarcolysin
  • L-phenylalanine mustard (L-PAM)
  • L-Sarcolysin phenylalanine mustard
  • L-sarcolysine
Drug: Cyclosporine
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:
  • Cyclosporin
  • Cyclosporin A
  • Ciclosporin
  • CSP
Radiation: Total lymphoid irradiation
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 Name: TLI
Biological: Rabbit anti-thymocyte globulin
ATG 1.5 mg/kg is administered intravenously (IV) on Day -11 to -7 before allo-PBSC infusion.
Other Names:
  • Thymoglobulin
  • ATG
Drug: Mycophenolate Mofetil 250mg
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:
  • CellCept
  • MMF
Drug: Solumedrol
Solumedrol 1 mg/kg is administered intravenously (IV) on Day -11 to -7 as a premedication for ATG and allo-PBSC infusion
Other Names:
  • Solumedin
  • Soludecadron
Drug: Diphenhydramine
Diphenhydramine 25 to 50 mg is administered as a premedication for the ATG; allo-PBSC; and DLI infusions.
Other Name: Benadryl
Drug: Acetaminophen
Acetaminophen 650 mg is administered as a premedication for the ATG and allo-PBSC infusions.
Other Name: Tylenol
Drug: Hydrocortisone
Hydrocortisone 100 mg is administered intravenously (IV) is a premedication for the allo-PBSC and DLI infusions.

Detailed Description:
Development of cell-based immunotherapy from allogeneic hematopoietic cell transplantation (HCT) is dependent upon stable T-cell engraftment and the success of this therapeutic approach is likely to be greatest when directed against a minimal rather than gross tumor burden. To this end, tandem transplants with high dose therapy and autologous hematopoietic cell transplantation (AHCT) for tumor cytoreduction followed by non-myeloablative allotransplant have been conducted. In myeloma, this tandem approach results in greater efficacy compared to conventional AHCT.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00899847


Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Investigators
Principal Investigator: Wen-Kai Weng Stanford University
  More Information

Responsible Party: Wen-Kai Weng, Assistant Professor of Medicine (Blood and Marrow Transplantation), Stanford University
ClinicalTrials.gov Identifier: NCT00899847     History of Changes
Other Study ID Numbers: IRB-15772
SU-04142009-2259 ( Other Identifier: Stanford University )
BMT201 ( Other Identifier: OnCore Number )
First Submitted: May 8, 2009
First Posted: May 12, 2009
Results First Submitted: August 24, 2017
Results First Posted: October 20, 2017
Last Update Posted: October 20, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Cyclosporins
Cyclosporine
Melphalan
Thymoglobulin
Antilymphocyte Serum
Allopurinol
Mechlorethamine
Mycophenolic Acid
Methylprednisolone Hemisuccinate
Prednisolone
Lenograstim
Promethazine
Acetaminophen
Diphenhydramine
Methylprednisolone