Lenalidomide and High Dose Melphalan Followed by Autologous Stem Cell Transplant in Multiple Myeloma

NCT01142232 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 1005-06; IUCRO-0290
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is a research study for newly diagnosed multiple myeloma or multiple myeloma has returned (relapsed). Multiple myeloma is a type of cancer that begins in white blood cells called plasma cells. Plasma cells make proteins that help fight infections. Current therapy for multiple myeloma includes high dose chemotherapy and autologous (patient's own cells) stem cell transplantation. There will be two parts (or phases) to this study: The purpose of the first part is to find the highest dose of a drug called lenalidomide (Revlimid®) that can be given in combination with high dose melphalan without causing severe adverse events. The purpose of the second part is to find out the effects of this treatment (good and bad) on multiple myeloma patients.

Conditions

Multiple Myeloma

Keywords

autologous stem cell transplantation

Outcome Measures

Primary Outcomes (2)

• Phase I: Number of Patients With Dose Limiting Toxicity

  The number of patients who had a DLT during the dose finding portion (Phase I) of the trial for the safety of lenalidomide when used in combination with high dose melphalan in the setting of autologous stem cell transplantation in patients with multiple myeloma.

  up to 1 month

• Phase II: Overall Response Rate

  Evaluate the overall response rate of patients receiving therapy. Patients are considered as having a response if their overall response is Partial Response or better (CR+sCR+VGPR+PR). The percentage of patients achieving this and the exact 95% confidence interval will be calculated. Responses will be defined using the response criteria determined by the International Working Group for Multiple Myeloma (CR= Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and 5% plasma cells in bone marrow; sCR=CR as defined above plus normal FLC ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunoflurorescence; VGPR=Serum and urine M-component detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-component plus urine M-component\<100 mg per 24 h; PR=\>=50% reduction of serum M-protein and reduction in 24-h urinary M-protein by \>=90% or to \<200mg per 24 h).

  up to 5 years

Secondary Outcomes (1)

• Phase II: Treatment-Related Adverse Events Grade 3 or Higher

  up to 5 years

Study Arms (1)

Melphalan with lenalidomide

EXPERIMENTAL

Melphalan will be given on Day -2 and Day -1. Lenalidomide will be given from Day -7 to Day +2.

Drug: Lenalidomide plus Melphalan during autologous stem cell transplantation; Drug: Lenalidomide maintenance

Interventions

Lenalidomide plus Melphalan during autologous stem cell transplantation DRUG

Patients will receive a fixed dose of melphalan, while the dose of lenalidomide is escalated according to the protocol defined cohorts. Lenalidomide is given on day -7 to day +2, while intravenous melphalan is given on day -2 and -1. Lenalidomide dosing will be in the morning at approximately the same time each day.

Melphalan with lenalidomide

Lenalidomide maintenance DRUG

Lenalidomide maintenance therapy will begin on Day +100 to Day +110 provided the protocol-defined criteria are met. The initial starting dose of lenalidomide during maintenance is 10 mg daily on Days 1-28 of each 28-day cycle.

Melphalan with lenalidomide

Eligibility Criteria

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

You may qualify if:

• Phase I: Patients with diagnosis of multiple myeloma at any stage of disease undergoing high dose chemotherapy and stem cell transplantation.
• Phase II: Patients with myeloma undergoing a first high dose chemotherapy and stem cell transplantation after achieving at least stable disease following induction therapy. Any induction regimen prior to transplantation is allowed. No more than 2 prior lines of therapy prior to transplantation are allowed.
• All previous therapy not associated with peripheral blood stem cell transplant, including radiation, hormonal therapy, and surgery, must have been discontinued 4 weeks prior to treatment in this study.
• ECOG performance status of \</= 2 at study entry
• Laboratory test results within protocol-specified ranges
• All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®
• Females of childbearing potential must have negative pregnancy test within 24 hours of first prescription for lenalidomide and must commit to either continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control.
• Able to take aspirin daily as prophylactic anticoagulation
• Subject must have the minimum stem cell dose of 5.0 x 10\^6 CD34+ cells/kg collected.

You may not qualify if:

• Pregnant or breast feeding females
• History of intolerance or resistance to lenalidomide
• Known hypersensitivity to thalidomide
• The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
• Known seropositive for or active viral infection with human immunodeficiency vrus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis b virus vaccine are eligible.

Sponsors & Collaborators

• Attaya Suvannasankha: lead
• Celgene: collaborator

Study Sites (1)

IU Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Lenalidomide

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

Results Point of Contact

• Title: Dr. Attaya Suvannasankha
• Organization: IndianaU

asuvanna@iu.edu

(317) 278-9306

Study Officials

• Attaya Suvannasankha, MD

  Indiana University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Clinical Medicine

Model Details: All patients will receive melphalan 100 milligrams (mg) per meters squared (m2) intravenously day -2 and day -1. Phase I patients will be enrolled sequentially into one of dose levels below and administered the corresponding lenalidomide dose. The recommended phase II dose based on dose limiting toxicities observed in the phase I portion will be used for lenalidomide dosing in the phase II portion of the trial Dose level -1 Lenalidomide 25 mg daily day -7 to day +2, Dose level 1 Lenalidomide 50 mg daily day -7 to day +2, Dose level 2 Lenalidomide 75 mg daily day -7 to day +2, Dose level 3 Lenalidomide 100 mg daily day -7 to day +2, Dose level 4 Lenalidomide 150 mg daily day -7 to day +2,

Study Record Dates

• First Submitted: June 10, 2010
• First Posted: June 11, 2010
• Study Start: August 27, 2010
• Primary Completion: November 6, 2015
• Study Completion: May 18, 2019
• Last Updated: October 22, 2019
• Results First Posted: October 22, 2019

Record last verified: 2019-10

Locations

US (1)