Trial of High Dose Melphalan/Stem Cell Transplant With or Without Bortezomib

NCT02489500 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: H-33808VelRand
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Standard treatment for AL Amyloidosis is high-dose melphalan and stem cell transplant. This study will compare the safety and effectiveness of standard treatment with high-dose melphalan and stem cell transplant, compared with investigational bortezomib when used in combination with standard treatment with high-dose melphalan and stem cell transplant for AL amyloidosis.

Conditions

AL Amyloidosis

Keywords

AL Amyloidosis; Stem Cell Transplantation

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Hematologic Response

  Hematologic response defined as: at least 50% improvement in the difference between involved and uninvolved free light chains

  6 months

Secondary Outcomes (3)

• Toxicities

  100 days

• Overall Survival

  5 years

• Number of Participants With Organ Response

  5 years

Study Arms (2)

melphalan

ACTIVE COMPARATOR

Neupogen 16mcg/kg x 4 days Stem cell collection Drug: high dose melphalan 140 or 200 mg/m2 stem cell infusion

Drug: Melphalan; Drug: Neupogen; Procedure: Stem Cell Collection; Procedure: Stem cell infusion

melphalan + Bortezomib

EXPERIMENTAL

Neupogen 16mcg/kg x 4 days Stem Cell collection drug: high-dose melphalan 140 or 200 mg/m2 drug: Bortezomib 1.0 mg/m2/dose x 4 doses stem cell infusion

Drug: Bortezomib; Drug: Melphalan; Drug: Neupogen; Procedure: Stem Cell Collection; Procedure: Stem cell infusion

Interventions

Bortezomib DRUG

Conditioning Regimen: Drug: Bortezomib: 1.0 mg/m2/dose D -6, D -3, D +1, D + 4 Drug: Melphalan: 70-100 mg/m2/dose D -2, D -1

Also known as: VELCADE

melphalan + Bortezomib

Melphalan DRUG

Conditioning Regimen: Drug: Melphalan: 70-100 mg/m2/dose D -2, D -1 Stem Cell Transplant: D 0

Also known as: Alkeran

melphalan; melphalan + Bortezomib

Neupogen DRUG

granulocyte colony-stimulating factor (G-CSF) mobilization 16mcg/kg x 4 days

Also known as: granulocyte colony-stimulating factor (G-CSF)

melphalan; melphalan + Bortezomib

Stem Cell Collection PROCEDURE

collect at least 2.5 million cluster of differentiation 34 (CD34)+ stem cells

Also known as: apheresis

melphalan; melphalan + Bortezomib

Stem cell infusion PROCEDURE

infusion of previously collected autologous stem cells

Also known as: infusion

melphalan; melphalan + Bortezomib

Eligibility Criteria

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

You may qualify if:

• Histological diagnosis of primary systemic (AL) amyloidosis based on:
• Deposition of amyloid material by Congo red stain showing characteristic apple green birefringence,AND…
• evidence of a clonal plasma cell dyscrasia with monoclonal protein in the serum or urine by immunofixation electrophoresis studies AND/OR abnormal serum free light chain assay AND/OR clonal plasma cells in the bone marrow exam demonstrated by immunohistochemistry, flow cytometry or in situ hybridization AND…
• evidence of organ involvement other than carpal tunnel syndrome. Patients with senile, secondary, localized, dialysis-related or familial amyloidosis are not eligible. Confirmation of tissue diagnosis at all sites of organ dysfunction is encouraged, but not required.
• Patients must be \> 18 years of age.
• Patients must have a performance status of 0-2 by Eastern Cooperative Oncology Group (ECOG) criteria
• Patients must have left ventricular ejection fraction (LVEF) \> 45% by echocardiogram within 60 days of enrollment
• Pulmonary Function Tests must show diffusing capacity of lung for carbon monoxide (DLCO) \> 50%.
• All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.

You may not qualify if:

• Patients with recent (\< 6 months) myocardial infarction, congestive heart failure, New York Heart Association (NYHA) class III/IV or arrhythmia which are refractory to medical therapy are ineligible.
• Prior chemotherapy with alkylating agent allowed only if no evidence of Myelodysplastic Dysplastic Syndrome (MDS) morphologically or cytogenetically. Total cumulative dose of oral melphalan must be \< 300 mg. Patients should not have received any cytotoxic therapy \< 4 weeks prior to registration and should have fully recovered from the effects of such therapy.
• Patients must not have overt multiple myeloma (\>30% bone marrow plasmacytosis and, extensive (\>2) lytic lesions and hypercalcemia).
• No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease-free for 5 years.
• Patients must not be HIV positive.
• Pregnant or nursing women may not participate. Women and men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.

Sponsors & Collaborators

• Boston Medical Center: lead

Study Sites (1)

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

MeSH Terms

Conditions

Immunoglobulin Light-chain Amyloidosis

Interventions

Bortezomib; Melphalan; Filgrastim; Granulocyte Colony-Stimulating Factor; Blood Component Removal

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Amyloidosis; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Paraproteinemias

Intervention Hierarchy (Ancestors)

Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Proteins; Biological Factors; Therapeutics

Limitations and Caveats

Early termination after enrollment held for toxicity evaluation; then closed due to competing trial.

Results Point of Contact

• Title: Vaishali Sanchorawala, MD
• Organization: Boston Medical Center

sfenness@bu.edu

6176388261

Study Officials

• Vaishali Sanchorawala, MD

  Boston Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 9, 2015
• First Posted: July 3, 2015
• Study Start: June 1, 2015
• Primary Completion: April 28, 2017
• Study Completion: April 28, 2017
• Last Updated: September 10, 2018
• Results First Posted: August 6, 2018

Record last verified: 2018-08

Locations

US (1)