Velcade, Doxil, and Dexamethasone (VDd) as First Line Therapy for Multiple Myeloma

This study has been completed.
Sponsor:
Information provided by:
University of Michigan Cancer Center
ClinicalTrials.gov Identifier:
NCT00116961
First received: June 30, 2005
Last updated: February 5, 2012
Last verified: February 2012
  Purpose

This is a research study for patients with newly diagnosed multiple myeloma. Multiple myeloma remains a non-curable disease however, newer medications and their combinations appear to provide higher response rates and higher complete response rates than current treatment options. One of the new medications in multiple myeloma is Velcade. Preliminary results from a study using a combination of Velcade with Doxil have shown high response rates (disease reduction). Preliminary results also show that an addition of dexamethasone to Velcade in patients not responding to Velcade alone showed improved response rates. This study involves treatment with a new combination of three standard medications: Velcade, Doxil, and dexamethasone (VDd combination). The proposed combination of all three drugs may improve efficacy and response.

Velcade is approved by the Food and Drug Administration (FDA) for treatment in multiple myeloma patients who have received at least two prior therapies and have demonstrated disease progression on the last therapy. Velcade is still currently under investigation for other indications. Doxil is not approved for use in multiple myeloma but is an approved drug for use in patients with some other cancers. Several published clinical trials provide evidence that Doxil is an active agent in multiple myeloma and it is used in treatment combinations for multiple myeloma in general practice. Dexamethasone is a standard therapy for multiple myeloma, but is not approved by the FDA for that use. The combination of all three drugs is experimental (not FDA approved).

The goals of this study are to determine if this new combination therapy with Velcade, Doxil and dexamethasone is an effective treatment and also to determine the side effects that occur when this combination treatment is given.


Condition Intervention Phase
Multiple Myeloma
Drug: Velcade
Drug: Doxil
Drug: Dexamethasone
Phase 2

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: A Phase II Study of Combination of Velcade, Doxil, and Dexamethasone (VDd) as First Line Therapy for Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by University of Michigan Cancer Center:

Enrollment: 40
Study Start Date: June 2005
Study Completion Date: December 2007
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
Detailed Description:

Multiple myeloma remains a non-curable disease. Initial therapy with one of the commonly used regimens, such as thalidomide with dexamethasone, VAD, dexamethasone pulses, and melphalan with prednisone results in at least partial response (PR) in approximately 50-75% of patients. Complete responses (CRs) with any of these regimens are uncommon. A proportion of patients will have further improvement of response after autologous stem cell transplant, which usually follows initial therapy. However, virtually all patients will eventually relapse and will require re-treatment. Emerging data suggests that achieving CR or near CR after transplantation will result in a more durable remission and longer survival. It is not clear whether CR in response to initial therapy and prior to transplant may have similar impacts on overall outcomes.

Newer agents and their combinations appear to provide higher response rates and higher CR rates. One of the new active agents in multiple myeloma is Velcade (bortezomib, formerly known as PS-341). This molecule has a novel mechanism of action by specifically inhibiting the proteasome. In a reported phase II trial, Velcade as a single agent induced at least minimal responses (MR) in 35% of patients and CR in 4% of patients, and at least a stabilization of the disease in 59% of patients with heavily pretreated, relapsed/refractory multiple myeloma using strict SWOG criteria. Velcade alone is superior than dexamethasone pulses in a phase III randomized study in patients with at least one but no more than 3 lines of therapy. Preliminary reports indicate that combinations of Velcade with other active anti-myeloma agents appear to provide superior outcomes than Velcade alone. An additional 18% of patients responded when dexamethasone was combined with Velcade in a patient population refractory to Velcade alone. Velcade with Doxil was shown to produce high response rates in a phase I study with 60% PR rate and 20% CR rate and acceptable toxicity in patients with relapsed/refractory multiple myeloma. There is only limited data on the outcomes of treatment of newly diagnosed patients with myeloma with Velcade or its combinations. Velcade as a single agent has been shown to have impressive response rate in newly diagnosed patients with 55% percent of patients achieving at least PR and 77% of patients achieving at least MR as per preliminary report from a phase II study. Treatment with Velcade did not appear to affect stem cell collection.

Considering the high activity of Velcade alone in untreated patients and the superior activity of combinations of Velcade with either Doxil or dexamethasone, we propose combining all three agents as a VDd combination (i.e. Velcade, Doxil, and dexamethasone). We hypothesize that this combination will have similar or better efficacy compared to other commonly used combinations for initial therapy (i.e. thalidomide with dexamethasone, dexamethasone pulses, VAD or melphalan and prednisone) or Velcade alone and higher than these treatment regimens CR rate with acceptable toxicity.

  Eligibility

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

Inclusion Criteria:

Each patient must meet all of the following inclusion criteria to be enrolled in the study:

  • Histologic confirmation of multiple myeloma
  • Patients must have active multiple myeloma requiring first line treatment
  • At least 18 years of age
  • Female patient is either postmenopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e. hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and for 3 months after completing treatment.
  • Male patient agrees to use an acceptable method of contraception for the duration of the study and for 3 months after completing treatment.
  • Expected survival of at least 6 months
  • Patients with abnormal kidney function, including patients on dialysis, are eligible if kidney insufficiency is secondary to multiple myeloma.
  • Patients must have adequate liver functions
  • Patients may have received up to 2 weeks of high dose steroids. Prior steroid treatment for more than 2 weeks is allowed provided the treatment was given for neurological compromise.
  • Prior radiation therapy will be allowed but radiation therapy must be completed prior to registration.

Exclusion Criteria:

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

  • Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
  • Patient had a myocardial infarction within 6 months of enrollment, history of cardiac disease, or clinical evidence of congestive heart failure.
  • Patient previously received 250 mg/m2 or more of doxorubicin (or equivalent for other anthracyclines).
  • Patient is known to be human immunodeficiency virus (HIV)-positive (patients assessed to be at risk should be tested).
  • Patient is known to be hepatitis B surface antigen-positive or has known active hepatitis C infection (patients assessed by the investigator to be at risk should be tested)
  • Patient has Grade 2 or greater peripheral neuropathy within 14 days before enrollment.
  • Patient has hypersensitivity to bortezomib, boron or mannitol, conventional doxorubicin HCL or the components of Doxil, or other study drugs.
  • Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women.
  • Patient is currently receiving other investigational drug(s).
  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: NCT00116961

Locations
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
University of Michigan Cancer Center
Investigators
Principal Investigator: Andrzej J Jakubowiak, MD, PhD The University of Michigan Health System
  More Information

No publications provided

Responsible Party: Andrzej J. Jakubowiak, MD, PhD, University of Michigan Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00116961     History of Changes
Obsolete Identifiers: NCT00670072
Other Study ID Numbers: UMCC 2004.047
Study First Received: June 30, 2005
Last Updated: February 5, 2012
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Liposomal doxorubicin
Bortezomib
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids

ClinicalTrials.gov processed this record on August 21, 2014