Bendamustine, Wkly Bortezomib, Lenalidomide and Dexamethasone for Multiple Myeloma (BVRD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by Loyola University
Sponsor:
Information provided by (Responsible Party):
Loyola University
ClinicalTrials.gov Identifier:
NCT01484626
First received: November 28, 2011
Last updated: October 29, 2012
Last verified: October 2012
  Purpose

The purpose of the study is to determine the safety and efficacy of the use of Bendamustine in combination with a commonly used combination chemotherapy to treat relapsed and refractory multiple myeloma. The study will be conducted in two phases. Participants in phase I will receive 1 of 4 escalating doses of bendamustine. Once the maximum tolerated dose of bendamustine is determined phase II of this trial will begin. Participants in phase II will receive the maximum tolerated dose of bendamustine in combination with standard of care chemotherapy.


Condition Intervention Phase
Multiple Myeloma
Drug: Bendamustine
Drug: Bortezomib
Drug: Lenalidomide
Drug: Dexamethasone
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label Phase I/II Study of Bendamustine, Weekly Bortezomib, Lenalidomide and Dexamethasone for the Treatment of Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Loyola University:

Primary Outcome Measures:
  • Maximally Tolerated Dose of Bendamustine [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]
    Primary objective of this phase is to determine the MTD of bendamustine when combined with bortezomib, lenalidomide and dexamethasone in subjects with relapsed and/or refractory multiple myeloma.


Secondary Outcome Measures:
  • Drug Toxicity [ Time Frame: 21 days ] [ Designated as safety issue: Yes ]

    toxicity is defined as the inability to complete cycle 1 due to the following: Grade 3 or higher non-hematologic toxicity that are clearly not related to disease progression or intercurrent illness

    • nausea, vomiting, diarrhea,
    • Grade 3 or 4 venous thromboembolic events
    • Grade 4 hematologic toxicity defined as: thrombocytopenia with platelets less than or equal to 10,000 on more than one occasion despite transfusion support

  • Survival [ Time Frame: 168 days ] [ Designated as safety issue: Yes ]
    The secondary objectives of the phase II portion of this study are to identify Median Progression-free survival, Median Overall Survival, Median Time to Next Treatment, and to identify any prognostic features that correlate to improved response.

  • Response Rates [ Time Frame: 168 days ] [ Designated as safety issue: Yes ]
    The primary objective of the phase II portion of this study is to determine the overall response rate (Minor Response (MR), partial response (PR), very good partial response (VGPR), complete response (CR), and stringent complete response (SCR) in patients treated with bendamustine in combination with weekly bortezomib, plus lenalidomide and dexamethasone. ORR will be calculated as the percentage of patients who achieve a MR or better after up to 8 cycles of protocol therapy.


Estimated Enrollment: 76
Study Start Date: May 2011
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Bendamustine
Phase I of the study will determine the safest dose of Bendamustine that can be combined with standard chemotherapy. Bendamustine will be given in doses of 25, 50, 75, 100, and 125 mg/m2. The first group of 3 patients to enter the study will receive a 25 mg/m2 dose of Bendamustine. If this dose is found to be safe, the next 3 patients will receive 50 mg/m2. The dose will continue to increase until the maximum tolerated dose (MTD)is found. Once the MTD is found the study will progress to phase II.
Drug: Bendamustine
The first group of 3 patients to enter the study will receive a 25 mg/m2 dose of Bendamustine. If this dose is found to be safe, the next 3 patients will receive 50 mg/m2. The dose will continue to increase until the highest safe dose of Bendamustine is found. Bendamustine and Bortezomib will be given through a catheter twice a week every 21 days. Dexamethasone and Lenalidomide will be given orally. In general, a cycle of chemotherapy will last 21 days.
Other Name: Treanda
Drug: Bortezomib
Bortezomib will be given through a catheter twice a week every 21 days.
Other Name: Velcade
Drug: Lenalidomide
Lenalidomide will be given orally taken as instructed by the physician.
Other Name: Revlimid
Drug: Dexamethasone
Dexamethasone will be given orally as instructed by the physician.
Other Name: Steroid

Detailed Description:

Multiple myeloma is a multi-organ neoplastic disorder caused by the clonal proliferation of plasma cells. It has an incidence of about 4.5/100,000 per year in the U.S., making it the second most common hematologic malignancy. For many years, alkylating agents have been the backbone of treatment. The combination of melphalan and prednisone was, for many years, the standard of care for patients who were not candidates for autologous transplantation. Melphalan continues to be the primary conditioning agent for autologous transplant,and cyclophosphamide has also gained a foothold in the treatment of this disease.

The introduction of novel agents has fundamentally changed the landscape of treating this disease, although the true effects on survival are not yet known. Immunomodulatory agents and proteosome inhibitors, including thalidomide, lenalidomide and bortezomib, have been used in both newly diagnosed and relapsed patients. Currently, there is intense clinical research on the optimal way to combine these novel agents with the traditional backbones of treatment - including alkylators, with one another and, eventually, with the subsequent iterations of these classes of drugs. However, despite the therapeutic excitement surrounding this disease, nearly all patients will relapse, and cure remains an elusive goal for all but a rare handful.

  Eligibility

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

Inclusion Criteria:

  • Adults with relapsed and/or refractory myeloma who have received between 1-4 prior lines of therapy
  • must have adequate liver and renal function
  • ZPS of 2 or better
  • must have measurable disease

Exclusion Criteria:

  • Peripheral neuropathy of grade II or higher
  • Thrombocytopenia (platelets less than 50,000/uL)
  • Neutropenia (ANC<1000/uL)
  • AST or ALT >2.4 X ULN
  • Total bilirubin >1.5 X ULN
  • Creatinine clearance of less than 60mL/min (Phase I) and of 40mL/min or less (Phase II)
  • Patients with HIV
  • Patients with active hepatitis
  • Pregnant or lactating women
  • Individuals of child-bearing potential not using adequate contraception
  • Individuals unable to provide informed consent
  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: NCT01484626

Contacts
Contact: Laura Michaelis, MD 708-327-3216 lmichaelis@lumc.edu
Contact: Michelle Deutsch, RN 708-327-3022 mdeutsc@lumc.edu

Locations
United States, Illinois
Loyola Univ Med Cntr - Cardinal Bernardin Cancer Center Recruiting
Maywood, Illinois, United States, 60153
Contact: Laura Michaelis, MD    708-327-3216    lmichaelis@lumc.edu   
Contact: Michelle Deutsch, RN    708-327-3022    mdeutsc@lumc.edu   
Principal Investigator: Laura Michaelis, MD         
Sponsors and Collaborators
Loyola University
Investigators
Principal Investigator: Laura Michaelis, MD Loyola Univ Med Cntr - Cardinal Bernardin Cancer Cntr
  More Information

No publications provided

Responsible Party: Loyola University
ClinicalTrials.gov Identifier: NCT01484626     History of Changes
Other Study ID Numbers: 203145
Study First Received: November 28, 2011
Last Updated: October 29, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Loyola University:
Relapsed Multiple Myeloma
Refractory Multiple Myeloma
Bendamustine
Bortezomib
Lenalidomide
Dexamethasone
Treanda
Velcade
Revlimid

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
Bendamustine
Lenalidomide
Bortezomib
Nitrogen Mustard Compounds
Thalidomide
BB 1101
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 19, 2014