Bendamustine, Wkly Bortezomib, Lenalidomide and Dexamethasone for Multiple Myeloma

Multiple Myeloma Clinical Trial

— BVRD  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01484626
• Other study ID #: 203145
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: May 5, 2011
• Est. completion date: June 18, 2014

Study information

• Verified date: June 2018
• Source: Loyola University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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, most patients will relapse and a cure remains an elusive goal.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: June 18, 2014
• Est. primary completion date: June 18, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

• Zubrod Performance Status (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)

• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.4 X ULN

• Total bilirubin >1.5 X upper limit of normal (ULN)

• Creatinine clearance of less than 45 milliliters per minute (mL/min)

• 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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Bendamustine
The first group of three patients to enter the study will receive a 25 mg/m^2 dose of bendamustine. If this dose is found to be safe, the next three patients will receive 50 mg/m^2. Using a modified Fibonacci dose-escalation design, the dose will continue to increase at a rate of 25 mg/m^2 until the highest safe dose of bendamustine is found. The maximum dose will be 125 mg/m^2. 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.

Locations

Country	Name	City	State
United States	Loyola University Medical Center	Maywood	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Loyola University	Celgene

Country where clinical trial is conducted

United States, 

References & Publications (43)

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Papandreou CN, Daliani DD, Nix D, Yang H, Madden T, Wang X, Pien CS, Millikan RE, Tu SM, Pagliaro L, Kim J, Adams J, Elliott P, Esseltine D, Petrusich A, Dieringer P, Perez C, Logothetis CJ. Phase I trial of the proteasome inhibitor bortezomib in patients with advanced solid tumors with observations in androgen-independent prostate cancer. J Clin Oncol. 2004 Jun 1;22(11):2108-21. — View Citation

Pönisch W, Mitrou PS, Merkle K, Herold M, Assmann M, Wilhelm G, Dachselt K, Richter P, Schirmer V, Schulze A, Subert R, Harksel B, Grobe N, Stelzer E, Schulze M, Bittrich A, Freund M, Pasold R, Friedrich T, Helbig W, Niederwieser D; East German Study Group of Hematology and Oncology (OSHO). Treatment of bendamustine and prednisone in patients with newly diagnosed multiple myeloma results in superior complete response rate, prolonged time to treatment failure and improved quality of life compared to treatment with melphalan and prednisone--a randomized phase III study of the East German Study Group of Hematology and Oncology (OSHO). J Cancer Res Clin Oncol. 2006 Apr;132(4):205-12. Epub 2006 Jan 10. — View Citation

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* Note: There are 43 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Patients Experiencing a Toxicity	The number of patients experiencing at least one toxicity at the lowest dose of bendamustine. A toxicity is defined as one or more of the following: Upper respiratory infection; anemia; thrombocytopenia; neutropenia; shortness of breath on exertion; decreased appetite; nausea; neuropathy; anxiety; arthritis; and hypercalcemia.	21 days