Pegylated Liposomal Doxorubicin, Low Freq Dexamethasone & Revlimid (Dd-R) in Newly Diagnosed Multiple Myeloma (MM)

NCT00617591 | Completed Phase 2 Results DMC

• 4 other identifiers: MCC-14986106095dRV-MM-PI-10707OBCA990185
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the research study is to determine the response rates when Revlimid® is combined with Doxil® and Dexamethasone (Dd-R) in newly diagnosed Multiple Myeloma. The study will also evaluate the side effects caused by the combination of these three drugs. This therapy is investigational in the treatment of Multiple Myeloma. Revlimid® is a drug that alters the immune system and it may also interfere with the development of tiny blood vessels that help support tumor growth. Therefore, in theory, it may reduce or prevent the growth of cancer cells. Revlimid® is approved by the Food and Drug Administration (FDA) for specific types of myelodysplastic syndrome (MDS) and Multiple Myeloma, two different types of blood cancer. It is currently being tested in a variety of other cancer conditions. In this case it is considered experimental. Doxil® is a form of chemotherapy. It is approved by the FDA for the treatment of relapsed/ refractory Multiple Myeloma in combination with Velcade. Dexamethasone is a steroid. It is also approved by the FDA, but not for the treatment of Multiple Myeloma. It is considered a standard part of most myeloma therapies for newly diagnosed patients.

Conditions

Multiple Myeloma

Keywords

Lenalidomide; Revlimid; Pegylated Liposomal Doxorubicin; Doxil; Dexamethasone; Decadron

Outcome Measures

Primary Outcomes (2)

• Overall Response Rate (ORR) - Percentage of Participants With Partial Response or Better With Induction Regimen

  ORR assessed using International Myeloma Working Group Response Definitions. Partial Remission (PR): A greater than 50% reduction in the serum paraprotein, and if present, a greater than 90% reduction in the urine M protein excretion. Patients must also have a decrease by 50% in the size of soft tissue plasmacytoma. If serum and urine M protein are not measurable, a 50% or greater decreased in the difference of the involved and uninvolved free light chain. Very Good Partial Remission (VGPR): Detectable serum and urine M component on immunofixation but not on electrophoresis or 90% or greater reduction in serum M protein with less than 100 mg/24 h of urinary M protein. Complete Remission (CR): The presence of less than 5% bone marrow plasmacytosis and the disappearance of all evidence of serum and urine M-components on electrophoresis as well as by immunofixation. In addition, soft tissue plasmacytoma must have disappeared.

  24 Months

• Percentage of Participants With Very Good Partial Remission (VGPR) or Better

  Quality of response: % Complete Response (CR) + Very Good Partial Remission (VGPR) to induction Dd-R as assessed using International Myeloma Working Group Response Definitions. Very Good Partial Remission (VGPR): Detectable serum and urine M component on immunofixation but not on electrophoresis or 90% or greater reduction in serum M protein with less than 100 mg/24 h of urinary M protein. Complete Remission (CR): The presence of less than 5% bone marrow plasmacytosis and the disappearance of all evidence of serum and urine M-components on electrophoresis as well as by immunofixation. In addition, soft tissue plasmacytoma must have disappeared.

  24 Months

Secondary Outcomes (3)

• Median Progression Free Survival (PFS) in Months

  24 Months

• 2 Year Overall Survival (OS) Rate

  24 Months

• Occurrence of Induction Toxicities

  24 Months

Study Arms (1)

Induction and Maintenance Therapy

EXPERIMENTAL

Induction Phase Followed by Maintenance Therapy. Patients received lenalidomide 25 mg orally on days 1-21, dexamethasone 40 mg orally on days on 1-4, and Pegylated Liposomal Doxorubicin (PLD) 40 mg/m\^2 intravenously on day 1 (reduced to 30 mg/m\^2 after the initial 29 patients were treated). Cycles were repeated every 28 days. At the best response (4-8 cycles of induction), patients could proceed with either high-dose therapy or maintenance with lenalidomide and dexamethasone at the tolerated doses on the same schedule until disease progression. Dd-R: Lenalidomide (Revlimid®) combined with Pegylated Liposomal Doxorubicin (Doxil®) and Dexamethasone (Decadron®) as outlined in the Detailed Description.

Drug: Lenalidomide; Drug: Pegylated Liposomal Doxorubicin (PLD); Drug: Dexamethasone

Interventions

Lenalidomide DRUG

25 mg orally on days 1-21

Also known as: Revlimid®

Induction and Maintenance Therapy

Pegylated Liposomal Doxorubicin (PLD) DRUG

40 mg/m\^2 intravenously on day 1 (reduced to 30 mg/m\^2 after the initial 29 patients were treated)

Also known as: Doxil®

Induction and Maintenance Therapy

Dexamethasone DRUG

40 mg orally on days on 1-4

Also known as: Decadron®

Induction and Maintenance Therapy

Eligibility Criteria

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

You may qualify if:

• Signed informed consent form
• Able to adhere to the study visit schedule and other protocol requirements
• Diagnosed with active multiple myeloma and be considered to have active disease
• Measurable myeloma paraprotein levels in serum (≥ 0.5 g/dL) or urine (≥ 0.2 g excreted in a 24-hour urine collection sample).
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
• Performance status of 3 will be allowed if related to bony disease.
• Prior steroid therapy for up to 4 weeks will not exclude the patient from entering the study.
• Bilirubin \< 3.0
• Liver enzymes: alanine transaminase or aspartate transaminase (ALT or AST) \< 3 x upper limit of normal (ULN)
• Must have adequate bone marrow function:
• Absolute neutrophil count \> 1,000 cells/mm³ (1.0 x 10\^9/L). Patients with bone marrow \>50% plasma cells are permitted to have a neutrophil count of \< 1,000 cells/mm³.
• Platelets ≥ 50,000 cells/mm³. Patients with bone marrow \>50% plasma cells are permitted to have a Platelet count \< 50, 000 cells/mm³.
• Hemoglobin \> 8 g/dL (transfusion allowed to increase the Hgb)
• Must have adequate renal function: Creatinine ≤ 2.5 mg/dL
• Must have a 2-d echocardiogram indicating left ventricular ejection fraction (LVEF) ≥ 50% within 42 days prior to first dose of study drug

You may not qualify if:

• Ongoing severe infection requiring intravenous antibiotic treatment
• Life expectancy of \<3 months
• Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia.
• Patients receiving therapeutic dosages of steroids (dexamethasone 160mg per pulse \> 4 pulses) for multiple myeloma.
• Myocardial infarct within 6 months before enrollment, New York Heart Association (NYHA) Class II or greater heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities.
• Uncontrolled medical problems such as diabetes mellitus, coronary artery disease, hypertension, unstable angina, arrhythmias), pulmonary, hepatic and renal diseases unless renal insufficiency is felt to be secondary to multiple myeloma.
• Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
• Pregnant or breast feeding females
• Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
• Prior chemotherapy for multiple myeloma, except for radiation to symptomatic bony disease, plasmapheresis for hyperviscosity, kyphoplasty and/or vertebroplasty

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Celgene Corporation: collaborator
• Ortho Biotech Clinical Affairs, L.L.C.: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Related Publications (1)

• Baz RC, Shain KH, Hussein MA, Lee JH, Sullivan DM, Oliver EF, Nardelli LA, Nodzon LA, Zhao X, Ochoa-Bayona JL, Nishihori T, Dalton WS, Alsina M. Phase II study of pegylated liposomal doxorubicin, low-dose dexamethasone, and lenalidomide in patients with newly diagnosed multiple myeloma. Am J Hematol. 2014 Jan;89(1):62-7. doi: 10.1002/ajh.23587.

  PMID: 24030918 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Lenalidomide; liposomal doxorubicin; Dexamethasone; Calcium Dobesilate

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)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Results Point of Contact

• Title: Rachid Baz, M.D.
• Organization: H. Lee Moffitt Cancer Center and Research Institute

rachid.baz@moffitt.org

813-745-8212

Study Officials

• Rachid Baz, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2008
• First Posted: February 18, 2008
• Study Start: January 1, 2008
• Primary Completion: April 1, 2013
• Study Completion: April 1, 2013
• Last Updated: January 17, 2014
• Results First Posted: December 17, 2013

Record last verified: 2013-10

Locations

US (1)