Clinical trial NCT01142232: Lenalidomide and High Dose Melphalan Followed by Autologous Stem Cell Transplant in Multiple Myeloma
Official title: Phase I/II Study of Oral Lenalidomide and High Dose Melphalan Supported by Autologous Peripheral Blood Stem Cell Infusion for Patients With Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: autologous stem cell transplantation
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: Celgene
First posted: 2010-06-11
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Intervention model: SEQUENTIAL
Intervention model description: 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,
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Phase I: Number of Patients With Dose Limiting Toxicity
timeFrame: up to 1 month
measure: Phase II: Overall Response Rate
timeFrame: up to 5 years
Secondary outcomes:
measure: Phase II: Treatment-Related Adverse Events Grade 3 or Higher
timeFrame: up to 5 years
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: IU Simon Cancer Center
state: Indiana
Study officials:
affiliation: Indiana University School of Medicine
name: Attaya Suvannasankha, MD
role: PRINCIPAL_INVESTIGATOR
References: