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

NCT00899847 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: IRB-15772SU-04142009-2259BMT201
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Incidence of Graft Versus Host Disease (GvHD)

  To evaluate the incidence acute GvHD of this tandem autologous/allogeneic transplant setting

  2 years after the last participant is enrolled.

Secondary Outcomes (7)

• Median Time to Engraftment After Auto-PBSC Transplant

  1 month

• Median Time to Engraftment After Allo-PBSC Transplant

  1 month

• Overall Response Rate (ORR)

  1 year

• Complete Response Rate (CRR)

  1 year

• Partial Response Rate (PRR)

  1 year

Study Arms (1)

Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

EXPERIMENTAL

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; 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

Interventions

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

Also known as: auto-PBPC, Autologous peripheral blood progenitor cells (auto-PBPC) transplantation

Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

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.

Also known as: allo-PBSC, Allogeneic peripheral blood progenitor cells (allo-PBPC) transplantation

Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

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.

Also known as: Neupogen, Granulocyte colony-stimulating factor (G-CSF), r-metHuG-CSF

Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

Cyclophosphamide DRUG

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

Also known as: Ciclofosfamida, Ciclofosfamide, Claphene, CP monohydrate (CPM), CSP

Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

Melphalan DRUG

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

Also known as: L-Sarcolysin, L-phenylalanine mustard (L-PAM), L-Sarcolysin phenylalanine mustard, L-sarcolysine

Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

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.

Also known as: Cyclosporin, Cyclosporin A, Ciclosporin, CSP

Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

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.

Also known as: TLI

Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

Rabbit anti-thymocyte globulin BIOLOGICAL

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

Also known as: Thymoglobulin, ATG

Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

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

Also known as: CellCept, MMF

Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

Solumedrol DRUG

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

Also known as: Solumedin, Soludecadron

Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

Diphenhydramine DRUG

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

Also known as: Benadryl

Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

Acetaminophen DRUG

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

Also known as: Tylenol

Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

Hydrocortisone DRUG

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

Autologous-Allogeneic Peripheral Blood Stem Cell Transplant

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Stanford University: lead

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Transplantation; Filgrastim; Granulocyte Colony-Stimulating Factor; Cyclophosphamide; Melphalan; Cyclosporine; Antilymphocyte Serum; thymoglobulin; Mycophenolic Acid; Methylprednisolone Hemisuccinate; Calcium Dobesilate; Diphenhydramine; Acetaminophen; Hydrocortisone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Surgical Procedures, Operative; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Methylprednisolone; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Ethylamines; Amines; Benzhydryl Compounds; Acetanilides; Anilides; Amides; Aniline Compounds; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids

Results Point of Contact

• Title: Wen-Kai Weng, MD; Associate Professor of Medicine
• Organization: Stanford University School of Med

wkweng@stanford.edu

650-723-7689

Study Officials

• Wen-Kai Weng

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine (Blood and Marrow Transplantation)

Study Record Dates

• First Submitted: May 8, 2009
• First Posted: May 12, 2009
• Study Start: May 1, 2009
• Primary Completion: April 1, 2014
• Study Completion: December 1, 2014
• Last Updated: October 20, 2017
• Results First Posted: October 20, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)