Bortezomib and Dexamethasone Followed by High-Dose Melphalan and Stem Cell Transplantation for Primary (AL) Amyloidosis

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Boston Medical Center
ClinicalTrials.gov Identifier:
NCT01083316
First received: November 2, 2009
Last updated: December 17, 2013
Last verified: December 2013

November 2, 2009
December 17, 2013
September 2009
August 2013   (final data collection date for primary outcome measure)
Disease Response [ Time Frame: One year ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT01083316 on ClinicalTrials.gov Archive Site
  • To determine overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
  • To assess safety [ Time Frame: 100 days ] [ Designated as safety issue: Yes ]
    Using the NCI CTCAE, toxicities will be assessed
  • To determine toxicities [ Time Frame: 100 Days from transplant date ] [ Designated as safety issue: Yes ]
  • To determine overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Bortezomib and Dexamethasone Followed by High-Dose Melphalan and Stem Cell Transplantation for Primary (AL) Amyloidosis
Phase II Trial of Induction Therapy With Bortezomib and Dexamethasone Followed by High-Dose Melphalan and Stem Cell Transplantation in Patients With AL Amyloidosis

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.

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.

Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Amyloidosis
Drug: Bortezomib (Velcade) and Dexamethasone

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

Other Name: Velcade; Bortezomib;
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
30
December 2040
August 2013   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01083316
H-28441, X05292
Yes
Boston Medical Center
Boston Medical Center
Millennium Pharmaceuticals, Inc.
Principal Investigator: Vaishali Sanchorawala, MD Boston Medical Center
Boston Medical Center
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP