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

Phase 1

Completed

Conditions: Multiple Myeloma

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

Registration Number: NCT01142232

Lead Sponsor: Attaya Suvannasankha

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.

Detailed Description: Lenalidomide is a drug that interferes with the development of tiny blood vessels that help tumors grow. Lenalidomide in combination with dexamethasone is approved by the Food and Drug Administration (FDA) for the treatment of relapsed multiple myeloma. It is also approved for the treatment of specific types of myelodysplastic syndrome (MDS), another blood cancer. Other research studies using lenalidomide in combination with other drugs in subjects with newly diagnosed multiple myeloma also show good response rate.

High dose melphalan is approved by the FDA and is commonly used in multiple myeloma treatment prior to stem cell transplantation. This combination of lenalidomide, high-dose melphalan and stem cell transplantation has not been studied in newly diagnosed and relapsed multiple myeloma, so it is considered experimental. In research studies, "experimental" refers to a drug or procedure that has undergone basic laboratory testing and received approval from the US Food and Drug Administration (FDA) to be tested in human subjects. A drug or procedure may be approved by the FDA for use in one disease or condition, but be considered experimental in other diseases or conditions.

In this study, lenalidomide will be given together with melphalan (chemotherapy) with the hope that more disease will be killed before the stem cell transplant. Three months after the transplant, patients will take lenalidomide again with the hope that this will help prolong the time when the disease is in remission.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 60

Inclusion Criteria

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.

Exclusion Criteria

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Melphalan with lenalidomide	Lenalidomide maintenance	Melphalan will be given on Day -2 and Day -1. Lenalidomide will be given from Day -7 to Day +2.
Melphalan with lenalidomide	Lenalidomide plus Melphalan during autologous stem cell transplantation	Melphalan will be given on Day -2 and Day -1. Lenalidomide will be given from Day -7 to Day +2.

Primary Outcome Measures

Name	Time	Method
Phase I: Number of Patients With Dose Limiting Toxicity	up to 1 month	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.
Phase II: Overall Response Rate	up to 5 years	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).

Secondary Outcome Measures

Name	Time	Method
Phase II: Treatment-Related Adverse Events Grade 3 or Higher	up to 5 years	Number of unique patients who had a treatment-related (possible, probable or definite) adverse events that were graded 3 or higher.