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Completed

NCT Number: NCT00899847

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

To evaluate the toxicity and tolerability of this tandem autologous/allogeneic transplant approach for patients with advanced stage multiple myeloma.

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Key information

Conditions

Transplantation, Homologous Blood Protein Disorders Blood and Marrow Transplant (BMT) Cardiovascular Diseases Hematologic Diseases Hemic and Lymphatic Diseases Hemorrhagic Disorders Hemostatic Disorders Immune System Diseases Immunoproliferative Disorders Lymphoproliferative Disorders Multiple Myeloma Neoplasms Neoplasms by Histologic Type Neoplasms, Plasma Cell Paraproteinemias Transplantation, Autologous Vascular Diseases

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Stanford University School of Medicine

Stanford, California, 94305, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Autologous peripheral blood stem cells (auto-PBSC) transplantation

Procedure

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

Allogeneic peripheral blood stem cells (allo-PBSC) transplantation

Procedure

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

Filgrastim

Drug

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

Cyclophosphamide

Drug

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

melphalan

Drug

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

cyclosporine

Drug

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

Total lymphoid irradiation

Radiation

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: TLI

Rabbit Anti-Thymocyte Globulin

Biological

ATG 1.5 mg/kg is administered intravenously (IV) on Day -11 to -7 before allo-PBSC infusion.

Other names: Thymoglobulin, ATG

Mycophenolate Mofetil 250mg

Drug

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

Solumedrol

Drug

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

diphenhydramine

Drug

Diphenhydramine 25 to 50 mg is administered as a premedication for the ATG; allo-PBSC; and DLI infusions.

Other names: Benadryl

Acetaminophen

Drug

Acetaminophen 650 mg is administered as a premedication for the ATG and allo-PBSC infusions.

Other names: Tylenol

Hydrocortisone

Drug

Hydrocortisone 100 mg is administered intravenously (IV) is a premedication for the allo-PBSC and DLI infusions.

Primary outcomes

  1. 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 outcomes

  1. 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

  2. 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

  3. Overall Response Rate (ORR)

    Time frame: 1 year

    Overall response rate (ORR) = Complete Response Rate (CRR) + Partial Response Rate (PRR)

  4. 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

  5. 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.

  6. 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)

  7. 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)

Sponsors and collaborators

Lead sponsor

Stanford University

Other

Registry information

Official study 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

Important dates

Study start
2009
Primary completion
2014
Study completion
2014
First posted
May 12, 2009
Registry last updated
Oct 20, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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