Bortezomib/Dexamethasone (BD), Followed By Autologous Stem Cell Transplantation and Maintenance Bortezomib/Dexamethasone For the Initial Treatment of Monoclonal Immunoglobulin Deposition Disease (MIDD) Associated With Multiple Myeloma and AL Amyloidosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Memorial Sloan-Kettering Cancer Center
Sponsor:
Collaborator:
Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01383759
First received: June 27, 2011
Last updated: August 13, 2014
Last verified: August 2014
  Purpose

The goal of this clinical trial is to determine the toxicity and also the efficacy of a treatment that includes the following treatment: Two medications, bortezomib and dexamethasone (or BD), followed by autologous stem cell transplantation, and a prolonged course of treatment with bortezomib and dexamethasone after transplantation. This type of treatment has been very effective in multiple myeloma. However, there is little experience with this treatment in patients who have Monoclonal Immunoglobulin Deposition Disease (MIDD) or amyloidosis. The investigators and others have treated patients who have MIDD and amyloidosis with bortezomib and autologous stem cell transplantation and have had success with this treatment. But the combination of autologous transplant with BD given before and after the transplant is a new way of treating these diseases, which the investigators believe will be very effective.


Condition Intervention
Light Chain Deposition Disease (LCDD or MIDD)
Light Chain and Heavy Chain Deposition Disease (LHCDD or MIDD)
Monoclonal Immunoglobulin Deposition Disease (MIDD)
Amyloidosis
Drug: Bortezomib/Dexamethasone (BD), Followed By Autologous STC & Maintenance Bortezomib/Dexamethasone

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pilot Study of Bortezomib/Dexamethasone (BD), Followed By Autologous Stem Cell Transplantation and Maintenance Bortezomib/Dexamethasone For the Initial Treatment of Monoclonal Immunoglobulin Deposition Disease (MIDD) Associated With Multiple Myeloma and AL Amyloidosis

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • To examine the tolerability [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    of a 3-phase comprehensive treatment approach including induction with BD followed by risk adapted HDM/ASCT, followed by consolidation/maintenance therapy with BD in patients with MIDD and AL amyloidosis.

  • To examine the toxicity [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Toxicities will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 4.0. Safety measurements also will be evaluated by physical examination findings, vital signs assessments, clinical laboratory test results, and adverse events.


Secondary Outcome Measures:
  • To estimate the hematologic response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    [Complete Response (CR), Very Good Partial Response (VGPR) and Partial Response (PR)], achieved at 12 month, and at 24 months post-initiation of treatment following the 3-phase comprehensive treatment approach

  • To estimate the organ response rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    12 months and at 24 months post-initiation of treatment following the 3 phase comprehensive treatment approach including induction with BD, followed by risk adapted HDM/ASCT, followed by consolidation/maintenance therapy with BD in patients with MIDD and AL amyloidosis.

  • To estimate the time to hematologic progression [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    following the 3-phase comprehensive treatment approach including induction with BD, followed by risk adapted HDM/ASCT, followed by consolidation/maintenance therapy with BD in patients with MIDD and AL amyloidosis.


Estimated Enrollment: 35
Study Start Date: June 2011
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bortezomib/Dexamethasone (BD) , STC & Maintenance BD
This is a pilot study to gain information and estimate the toxicity/tolerability of 1-3 cycles of BD, followed by HDM/ASCT, and maintenance therapy with BD in patients with MIDD associated with multiple myeloma and AL amyloidosis.
Drug: Bortezomib/Dexamethasone (BD), Followed By Autologous STC & Maintenance Bortezomib/Dexamethasone

The treatment has three phases:

1) Initial treatment phase: This phase consists of 1-3 21-day-cycles of a combination regimen that includes bortezomib 1.3 mg/m2, IV or Subcutaneous Injection (SQ), on days 1, 4, 8, and 11; and dexamethasone 40 mg PO or IV, on days 1, 4, 8, and 11. Stem cell mobilization and HDM/ASCT. Post-ASCT consolidation/maintenance treatment phase: This phase consists of six cycles of bortezomib 1.3 mg/m2, IV or (SQ) with dexamethasone 20 mg PO or IV administered on days 1, 8, 15, and 22 every 12 weeks +/- 2 weeks.


  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age > or = to 18
  • New diagnosis of MIDD or AL amyloidosis based on pathologic findings confirmed at Memorial Sloan Kettering Cancer Center.
  • Patients must show the ability to understand the investigational nature of the treatment and to give voluntary 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 postmenopausal for at least 1 year before the screening visit, is surgically sterilized or if they are of childbearing potential, agree to practice 2 effective methods of contraception from the time of signing the informed consent form through 30 days after the last dose of bortezomib, or agree to completely abstain from heterosexual intercourse.
  • Male subjects, even if surgically sterilized (i.e., status post-vasectomy) must agree to 1 of the following: practice effective barrier contraception during the entire study treatment period and through a minimum of 30 days after the last dose of study drug, or completely abstain from heterosexual intercourse.
  • Adequate organ function defined as follows: Absolute granulocytes > 1,000/mm3 and platelets > 70,000/mm3, unless low granulocyte and platelets counts are due to multiple myeloma; total bilirubin < 1.5 ULN; AST, ALT, and alkaline phosphatase < 3 times upper limit of laboratory normal; LVEF > 50% by MUGA or ECHO (the method used at baseline must be used for later monitoring); DLCO > 50 % confirmed at MSKCC; elevated creatinine is not a contraindication to enrollment
  • Performance status (ECOG) < or = to 2

Exclusion Criteria:

  • Patient has received other investigational drugs with 14 days before enrollment
  • Prior initial treatment chemotherapy for MIDD, AL amyloidosis or multiple myeloma with the exception of one cycle of high dose dexamethasone
  • Prior bortezomib treatment
  • Myocardial infarction within 6 months prior to enrollment or New York Heart Association Class III or IV heart failure (see Appendix 20.2), 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.
  • Pregnant or lactating women are ineligible. A pregnancy test will be performed on each fertile premenopausal female 2 weeks prior to entry into the study. Treatment may not begin until the results of the pregnancy test are ascertained. All patients (men and women) must agree to use medically approved contraceptive measures for at least 4 weeks before starting therapy, during therapy, and for at least 3 months after therapy has stopped.
  • Pre existing neuropathy, sensory or neuropathic pain findings, grade 2 or higher on the NCI CTC neurotoxicity scale.
  • Concurrent active malignancy other than non melanoma skin cancers or carcinoma in situ of the cervix. Patients with previous malignancies, but which have not required anti tumor treatment within the preceding 24 months will be allowed to enter the trial. Patients with a history of a T1a or b prostate cancer (detected incidentally at TURP and comprising less than 5% of resected tissue) may participate if the PSA has remained within normal limits since TURP.
  • Patients with known HIV positivity or AIDS related illness. This is based upon the possibility of increasing HIV viral load with therapy
  • Any other medical condition or reason that, in the principal investigator's opinion, makes the patient unsuitable to participate in a clinical trial
  • Patients with a history of hypersensitivity reactions attributed to bortezomib, boron, or mannitol.
  • Radiation therapy within 3 weeks before randomization. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 3 weeks have elapsed since the last date of therapy.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01383759

Contacts
Contact: Hani Hassoun, MD 212-639-3228
Contact: Heather Landau, MD 212-639-8808

Locations
United States, New Jersey
Memorial Sloan-Kettering at Basking Ridge Recruiting
Basking Ridge, New Jersey, United States, 07920
Contact: Hani Hassoun, MD    212-639-3228      
United States, New York
Memorial Sloan-Kettering Cancer Center @ Suffolk Recruiting
Commack, New York, United States, 11725
Contact: Hani Hassoun, MD    212-639-3228      
Memorial Sloan-Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Hani Hassoun, MD    212-639-3228      
Contact: Heather Landau, MD    212-639-8808      
Principal Investigator: Hani Hassoun, MD         
Memorial Sloan-Kettering at Mercy Medical Center Recruiting
Rockville Centre, New York, United States
Contact: Hani Hassoun, MD    212-639-3228      
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center Recruiting
Sleepy Hollow, New York, United States, 10591
Contact: Hani Hassoun, MD    212-639-3228      
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Millennium Pharmaceuticals, Inc.
Investigators
Principal Investigator: Hani Hassoun, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01383759     History of Changes
Other Study ID Numbers: 11-061
Study First Received: June 27, 2011
Last Updated: August 13, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:
BORTEZOMIB (VELCADE)
CYCLOPHOSPHAMIDE (CYTOXAN)
DEXAMETHASONE
MELPHALAN
11-061

Additional relevant MeSH terms:
Amyloidosis
Multiple Myeloma
Neoplasms, Plasma Cell
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Metabolic Diseases
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Proteostasis Deficiencies
Vascular Diseases
Antibodies
BB 1101
Bortezomib
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Immunoglobulins
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Autonomic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on October 20, 2014