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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:
ClinicalTrials.gov Identifier:
NCT01083316
First Posted: March 9, 2010
Last Update Posted: May 12, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Vaishali Sanchorawala, Boston Medical Center
  Purpose

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.


Condition Intervention Phase
Amyloidosis Drug: Bortezomib Drug: Dexamethasone Drug: Melphalan Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Vaishali Sanchorawala, Boston Medical Center:

Primary Outcome Measures:
  • Number of Participants With Disease Response [ Time Frame: One year ]
    Complete response: Normal serum free light chain ratio and Negative serum and urine immunofixation electrophoresis Very good partial response: Difference in serum free light chains less than 40 mg/L Partial Response: >50% Reduction in the difference in serum free light chains

  • Number of Participants Surviving at 100 Days Post Transplant [ Time Frame: 100 days ]
  • Number of Participants Proceeding to Transplant Following Induction [ Time Frame: 2 months ]

Secondary Outcome Measures:
  • Number of Participants Surviving at 5 Years [ Time Frame: 5 years ]

Enrollment: 35
Study Start Date: September 2009
Estimated Study Completion Date: December 2040
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single Arm - Investigational

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

Drug: Bortezomib

Induction:

Velcade 1.3 mg/m2/dose 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

Other Name: Velcade
Drug: Dexamethasone

Induction:

Dexamethasone 20 mg PO/IV Days 1, 4, 8, 11 repeated every 21 days

Other Name: Decadron
Drug: Melphalan

Conditioning:

Melphalan 70-100 mg/m2/day IV on days -2 and -1

Other Name: Alkeran

Detailed 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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01083316


Locations
United States, Massachusetts
Boston Medical Center
Boston, Massachusetts, United States, 02118
Sponsors and Collaborators
Boston Medical Center
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Vaishali Sanchorawala, MD Boston Medical Center
  More Information

Additional Information:
Responsible Party: Vaishali Sanchorawala, Principal Investigator, Boston Medical Center
ClinicalTrials.gov Identifier: NCT01083316     History of Changes
Other Study ID Numbers: H-28441
X05292 ( Other Identifier: Millennium )
First Submitted: November 2, 2009
First Posted: March 9, 2010
Results First Submitted: December 13, 2016
Results First Posted: February 6, 2017
Last Update Posted: May 12, 2017
Last Verified: April 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Vaishali Sanchorawala, Boston Medical Center:
Amyloid
Amyloidosis
AL Amyloidosis
Primary Amyloidosis
Stem Cell Transplant

Additional relevant MeSH terms:
Amyloidosis
Proteostasis Deficiencies
Metabolic Diseases
Dexamethasone acetate
Dexamethasone
Bortezomib
Melphalan
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors