Bendamustine in Combination With Bortezomib and Pegylated Liposomal Doxorubicin for Multiple Myeloma

NCT01177683 | Terminated Phase 1 Results DMC

• 1 other identifier: MM08-141
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 7

Brief Summary

This is an open label phase I/II trial to determine the safety and the biologic activity of the bendamustine, bortezomib and pegylated liposomal doxorubicin combination.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Phase I: MTD of Bendamustine When Combined With Bortezomib and Pegylated Liposomal Doxorubicin.

  In the first phase, MTD of bendamustine was determined in combination with bortezomib and pegylated liposomal doxorubicin to gain a better idea of safe dosing before proceeding with the second phase to assess efficacy. Assuming myelosuppression being a dose-limiting effect that could have been overcome with growth factor support, MTD of the combination with myeloid growth factor support was also tested.

  From C1D1 up to a maximum of 7 months or until death

• Phase II : Overall Response Rate

  Overall response rate (CR+PR) of bendamustine in association with bortezomib and pegylated liposomal doxorubicin was assessed in patients with relapsed or refractory Multiple Myeloma. Per modified International Myeloma Working Group criteria: Complete Response (CR) : Negative for monoclonal protein by immunofixation on the serum and urine, and Disappearance of any soft tissue plasmacytomas, and \<5% plasma cells in bone marrow ; PR : 50% or more reduction in serum M-protein and 90% or more reduction in urine M-protein or to \<200 mg/24hours or a 50% or more reduction in free light chain level ; Overall Response (OR) = CR +PR.

  From C1D1 up to a maximum of 52 months or until death

Secondary Outcomes (5)

• Phase I & Phase II : Toxicity of Treatment Regimen

  From C1D1 until death or up to a maximum of 54 months

• Phase II : Time to Progression

  From C1D1 up to a maximum of 54 months or until death

• Phase II: Progression-free Survival (PFS)

  From C1D1 up to a maximum of 54 months until death

• Phase II: Duration of Survival

  From C1D1 up to a maximum of 52 months

• Phase II: Overall Survival

  From C1D1 up to a maximum of 54 months or until death

Study Arms (1)

Arm 1

EXPERIMENTAL

Bendamustine in combination with bortezomib and pegylated liposomal doxorubicin.

Drug: Bendamustine; Drug: Doxorubicin; Drug: Bortezomib; Drug: Filgrastim

Interventions

Bendamustine DRUG

Phase I component: Bendamustine escalating cohorts to determine MTD, IV over 1 hour, Days 1 and 4

Arm 1

Doxorubicin DRUG

Phase I and II components: Pegylated liposomal doxorubicin, 30 mg/m2 IV over 1 hour, Day 4

Arm 1

Bortezomib DRUG

Phase I and II components: Bortezomib 1.3 mg/m2 IV bolus, Days 1, 4, 8, and 11

Arm 1

Filgrastim DRUG

Phase II component: Filgrastim (if defined in MTD) 5 µg/kg/day SC, starting day 6 until neutrophil recovery to ANC \>1000

Arm 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A histologically established diagnosis of multiple myeloma with evidence of relapse or refractory disease.
• Must have a detectable serum or urine M-Protein by protein electrophoresis that is at least 500 mg/dL (serum) or 1 gm/24 hours (urine), respectively, or serum free light chain level \>100 mg/l for the involved free light chain.
• Must have received at least one (1) prior line of systemic treatment that has included either lenalidomide or thalidomide.
• Must be willing to provide correlative blood samples.

You may not qualify if:

• Must not have received an excessive cumulative dose of anthracycline
• No ≥ grade 2 peripheral neuropathy.
• No cytotoxic chemotherapy within 30 days prior to registration for protocol therapy.
• No autologous stem cell transplant within 6 months prior to registration for protocol therapy
• No prior radiation therapy to \> 25% of bone marrow forming bones (i.e., pelvis) within 30 days prior to registration for protocol therapy. See Study Procedures Manual to calculate percent of prior radiation.
• No current corticosteroid therapy in doses greater than 10 mg daily of prednisone (or equivalent) if given for management of co-morbid conditions.
• No known central nervous system involvement by myeloma.
• No poorly controlled intercurrent illness including, but not limited to, ongoing or active infection, poorly controlled diabetes, symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social climate that in the opinion of the investigator would limit compliance with study requirements.
• No patients known to be positive for HIV, or active Hepatitis A, B, or C.
• No major surgery within 30 days prior to registration for protocol therapy. Placement of a venous access device within 30 days prior to registration for protocol therapy is allowed.

Sponsors & Collaborators

• Sherif Farag, MB, BS: lead
• Hoosier Cancer Research Network: collaborator
• Cephalon, Inc.: collaborator

Study Sites (7)

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

IU Health Central Indiana Cancer Centers

Indianapolis, Indiana, 46219, United States

Location

Community Regional Cancer Center

Indianapolis, Indiana, 46256, United States

Location

IU Health Arnett Cancer Center

Lafayette, Indiana, 47904, United States

Location

Metro Health Cancer Care

Wyoming, Michigan, 49519, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

University Hospitals Seidman Cancer Center

Cleveland, Ohio, 44106, United States

Location

Related Links

• Hoosier Oncology Group Homepage

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Bendamustine Hydrochloride; Doxorubicin; Bortezomib; Filgrastim

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Annesha Majumdar
• Organization: Hoosier Cancer Research Network

amajumdar@hoosiercancer.org

3179212050

Study Officials

• Sherif Farag, M.B., B.S.

  Hoosier Cancer Research Network

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: August 5, 2010
• First Posted: August 9, 2010
• Study Start: July 1, 2010
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: October 6, 2023
• Results First Posted: October 6, 2023

Record last verified: 2023-09

Locations

US (7)