Overview

This trial is active, not recruiting.

Condition amyloidosis
Treatment bortezomib (velcade) and dexamethasone
Phase phase 2
Sponsor Boston Medical Center
Collaborator Millennium Pharmaceuticals, Inc.
Start date September 2009
End date August 2013
Trial size 30 participants
Trial identifier NCT01083316, H-28441, X05292

Summary

The drugs dexamethasone and bortezomib are both FDA-approved for the treatment of multiple myeloma, a disease very similar to amyloidosis. However, they are currently investigational for the treatment of amyloidosis.

We want to find out if the addition of dexamethasone and bortezomib to standard high dose chemotherapy and stem cell transplant can help improve response.

Standard treatment includes four steps: 1) Stem Cell Mobilization (standard) 2) Stem Cell Collection (standard) 3) Conditioning Regimen (Melphalan chemotherapy). The conditioning regimen helps to kill the abnormal cells in the body and makes room in the bone marrow for new blood stem cells to grow. 4) Stem Cell Infusion

Participants in this study will have an additional treatment step called "induction therapy", designed as the first step towards reducing the number of abnormal cells in the body. Two cycles of the investigational drugs bortezomib and dexamethasone will be given during induction therapy. In addition, bortezomib will given as part of the conditioning regimen, in addition to the standard melphalan chemotherapy.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Induction: Bortezomib (Velcade) 1.3 mg/m2/dose IV Days 1, 4, 8, 11 repeated every 21 days Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days Conditioning: Bortezomib 1.0 mg/m2/dose will be administered on Days +6, -3, +1, + 4 Melphalan 70-100 mg/m2/day IV on days -2 and -1
bortezomib (velcade) and dexamethasone Velcade; Bortezomib;
Induction: Velcade 1.3 mg/m2/dose IV Days 1, 4, 8, 11 repeated every 21 days Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days Conditioning: Bortezomib 1.0 mg/m2/dose will be administered on Days +6, -3, +1, + 4 Melphalan 70-100 mg/m2/day IV on days -2 and -1

Primary Outcomes

Measure
Disease Response
time frame: One year

Secondary Outcomes

Measure
To determine overall survival
time frame: 5 years
To assess safety
time frame: 100 days

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Histological diagnosis of primary systemic (AL) amyloidosis based on: 1. Deposition of amyloid material by congo red stain showing characteristic green birefringence, and 2. monoclonal light chain protein in the serum or urine or immunohistochemical studies or serum free light chain assay and 3. evidence of tissue involvement other than carpal tunnel syndrome, i.e. positive immunohistochemical staining of bone marrow demonstrating clonal plasma cells; or tissue amyloid deposits with anti-kappa or anti-lambda anti-serum; evidence for a plasma cell dyscrasia (PCD) by serum/urine or bone marrow; or overwhelmingly convincing clinical features e.g. macroglossia, associated with other systemic manifestations. Note: 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. - Must be at least 18 years of age. - Must have a performance status of 0-2 by Southwest Oncology Group criteria - Must have LVEF at least 45% by ECHO within 60 days of enrollment - 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 less than 300 mg. Patients should not have received any cytotoxic therapy less than 4 weeks prior to registration and should have fully recovered from the effects of such therapy. - Pulmonary Function Tests must show DLCO at least 50%. - Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. - Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. - Male subject agrees to use an acceptable method for contraception for the duration of the study. Exclusion Criteria: - No overt multiple myeloma (over 30% bone marrow plasmacytosis, extensive (great than 2) lytic lesions, 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 3 years. - No known to be HIV positive. - No platelet count of less than or equal to 70K within 14 days before enrollment. - No absolute neutrophil count of ANC less than or equal to 1000 within 14 days before enrollment. - No greater than or equal to Grade 2 peripheral neuropathy within 14 days before enrollment. - No myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see section 8.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant. - No hypersensitivity to bortezomib, boron or mannitol. - No pregnant or breast-feeding females. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. - Must not have received other investigational drugs with 14 days before enrollment - No serious medical or psychiatric illness likely to interfere with participation in this clinical study.

Additional Information

Official title Phase II Trial of Induction Therapy With Bortezomib and Dexamethasone Followed by High-Dose Melphalan and Stem Cell Transplantation in Patients With AL Amyloidosis
Principal investigator Vaishali Sanchorawala, MD
Description The drugs dexamethasone and bortezomib are both FDA-approved drugs for the treatment of multiple myeloma, a disease very similar to amyloidosis. However, they are currently investigational for the treatment of amyloidosis. The investigators want to find out if the addition of dexamethasone and bortezomib to standard treatment of high dose chemotherapy and stem cell transplant can help improve response to treatment.
Trial information was received from ClinicalTrials.gov and was last updated in January 2016.
Information provided to ClinicalTrials.gov by Boston Medical Center.