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

NCT ID: NCT00899847

Last Updated: 2017-10-20

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

9 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-05-31

Study Completion Date

2014-12-31

Brief Summary

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

Detailed Description

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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.

Conditions

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Transplantation, Homologous Transplantation, Autologous Multiple Myeloma Blood and Marrow Transplant (BMT)

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Autologous peripheral blood stem cells (auto-PBSC) transplantation

Intervention Type 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

Allogeneic peripheral blood stem cells (allo-PBSC) transplantation

Intervention Type PROCEDURE

Allo-PBSC (target collection ≥ 5 x 10e6 CD34+ cells/kg) are intravenously (IV) infused as part of the combination stem cell therapy.

Filgrastim

Intervention Type 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.

Cyclophosphamide

Intervention Type DRUG

Cyclophosphamide is administered intravenously (IV) at 4 g/m2 on Day 1 of the auto-PBSC mobilization regimen.

Melphalan

Intervention Type DRUG

Melphalan is administered after CSP at 200 mg/m2 intravenously (IV) on Day -2 before auto-PBSC infusion.

Cyclosporine

Intervention Type 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.

Total lymphoid irradiation

Intervention Type 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.

Rabbit anti-thymocyte globulin

Intervention Type BIOLOGICAL

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

Mycophenolate Mofetil 250mg

Intervention Type 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

Solumedrol

Intervention Type DRUG

Solumedrol 1 mg/kg is administered intravenously (IV) on Day -11 to -7 as a premedication for ATG and allo-PBSC infusion

Diphenhydramine

Intervention Type DRUG

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

Acetaminophen

Intervention Type DRUG

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

Hydrocortisone

Intervention Type DRUG

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

Interventions

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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

Intervention Type 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.

Intervention Type PROCEDURE

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.

Intervention Type DRUG

Cyclophosphamide

Cyclophosphamide is administered intravenously (IV) at 4 g/m2 on Day 1 of the auto-PBSC mobilization regimen.

Intervention Type DRUG

Melphalan

Melphalan is administered after CSP at 200 mg/m2 intravenously (IV) on Day -2 before auto-PBSC infusion.

Intervention Type 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.

Intervention Type DRUG

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.

Intervention Type RADIATION

Rabbit anti-thymocyte globulin

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

Intervention Type BIOLOGICAL

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

Intervention Type DRUG

Solumedrol

Solumedrol 1 mg/kg is administered intravenously (IV) on Day -11 to -7 as a premedication for ATG and allo-PBSC infusion

Intervention Type DRUG

Diphenhydramine

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

Intervention Type DRUG

Acetaminophen

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

Intervention Type DRUG

Hydrocortisone

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

Intervention Type DRUG

Other Intervention Names

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auto-PBPC Autologous peripheral blood progenitor cells (auto-PBPC) transplantation allo-PBSC Allogeneic peripheral blood progenitor cells (allo-PBPC) transplantation Neupogen Granulocyte colony-stimulating factor (G-CSF) r-metHuG-CSF Ciclofosfamida Ciclofosfamide Claphene CP monohydrate (CPM) CSP L-Sarcolysin L-phenylalanine mustard (L-PAM) L-Sarcolysin phenylalanine mustard L-sarcolysine Cyclosporin Cyclosporin A Ciclosporin CSP TLI Thymoglobulin ATG CellCept MMF Solumedin Soludecadron Benadryl Tylenol

Eligibility Criteria

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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.


* 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

Exclusion Criteria

* Prior allogeneic hematopoietic cell transplantation
* Uncontrolled active infection
* Uncontrolled congestive heart failure or angina
* HIV-positive
* Pregnant or nursing


* Serious medical or psychological illness
* Pregnant or lactating
* Prior malignancies within the last 5 years except for non-melanoma skin cancers
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Stanford University

OTHER

Sponsor Role lead

Responsible Party

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Wen-Kai Weng

Assistant Professor of Medicine (Blood and Marrow Transplantation)

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Wen-Kai Weng

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

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Stanford University School of Medicine

Stanford, California, United States

Site Status

Countries

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United States

Other Identifiers

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SU-04142009-2259

Identifier Type: OTHER

Identifier Source: secondary_id

BMT201

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-15772

Identifier Type: -

Identifier Source: org_study_id