Lenalidomide in Treating Patients With Multiple Myeloma Undergoing Autologous Stem Cell Transplant

Phase 3

Active, not recruiting

Conditions: DS Stage I Multiple Myeloma
Smoldering Multiple Myeloma
DS Stage II Multiple Myeloma
DS Stage III Multiple Myeloma
Refractory Multiple Myeloma

Interventions: Procedure: Autologous Hematopoietic Stem Cell Transplantation
Other: Laboratory Biomarker Analysis
Drug: Lenalidomide
Drug: Melphalan
Procedure: Peripheral Blood Stem Cell Transplantation
Other: Placebo Administration

Registration Number: NCT00114101

Lead Sponsor: National Cancer Institute (NCI)

Brief Summary: This randomized phase III trial studies lenalidomide to see how well it works compared to a placebo in treating patients with multiple myeloma who are undergoing autologous stem cell transplant. Giving chemotherapy before a peripheral blood stem cell transplant helps kill any cancer cells that are in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Biological therapies, such as lenalidomide, may stimulate or suppress the immune system in different ways and stop cancer cells from growing. Giving lenalidomide after autologous stem cell transplant may be an effective treatment for multiple myeloma.

Detailed Description: PRIMARY OBJECTIVE:

I. To determine the efficacy of CC-5013 (lenalidomide) in prolonging time to disease progression in patients with multiple myeloma after autologous stem cell transplant (ASCT).

SECONDARY OBJECTIVES:

I. To determine if CC-5013 will increase the complete response (CR) rate in patients with multiple myeloma following ASCT.

II. To compare the progression-free survival (PFS) and overall survival (OS) in patients with multiple myeloma who have undergone ASCT and who then are randomized to either CC-5013 or placebo.

III. To determine the feasibility of long-term administration of CC-5013 to multiple myeloma patients who have undergone ASCT.

OUTLINE:

PERIPHERAL BLOOD STEM CELL (PBSC) MOBILIZATION: Mobilization of autologous PBSC will be performed according to institutional guidelines.

AUTOLOGOUS PBSC TRANSPLANTATION (PBSCT): Patients receive melphalan intravenously (IV) over 30-60 minutes on day -2 or -1 or over 2 days on days -3 and -2 or -2 and -1. Patients undergo autologous PBSCT on day 0.

Patients are then randomized to 1 of 2 maintenance treatment arms. (Note: As of 12/17/09, no more patients will be randomized between lenalidomide and placebo. Patients who have not been randomized as of 12/17/09 will be assigned to lenalidomide.)

ARM I: Beginning between day 100-110, patients receive lenalidomide orally (PO) once daily.

ARM II: Beginning between day 100-110, patients receive placebo (PO) once daily.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months thereafter.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 460

Inclusion Criteria

Patients must have active multiple myeloma requiring treatment (Durie-Salmon stage >= 1) and have stable disease or be responsive to at least 2 months of any induction therapy; patients with smoldering myeloma are not eligible unless the disease has progressed to >= stage 1
No more than 12 months of any prior therapy, including CC-5013 and thalidomide
Within 12 months of initiation of induction therapy
No prior progression after initial therapy; in addition, no more than two regimens will be allowed excluding dexamethasone alone
No prior peripheral blood, bone marrow, or solid organ transplant
Patients must have peripheral blood stem cell collection of >= 2 x 10^6 cluster of differentiation (CD)34+ cells/kg (patient body weight) and preferably 5 x 10^6 cells/kg (patient body weight); stem cells may be collected at any time prior to transplant; peripheral blood stem cell collection may occur before or after registration
Patients must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Patients must have diffusing capacity of the lung for carbon monoxide (DLCO) > 50% predicted with no symptomatic pulmonary disease
Patients must have left ventricular ejection fraction (LVEF) >= 40% by multi gated acquisition scan (MUGA) or echocardiogram
Patients must not have uncontrolled diabetes mellitus
Patients must not have an active serious infection
Patients must not be human immunodeficiency virus (HIV), hepatitis B surface antigen (HBSag), or hepatitis (Hep) C positive
Patients must be non-pregnant and non-nursing; women of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL 10-14 days prior to registration and repeated within 24 hours prior to the first dose of lenalidomide; in addition, women of childbearing potential taking lenalidomide must have a pregnancy test performed by the doctor weekly during the first 4 weeks of treatment, and then every 4 weeks if menses are regular and every 2 weeks if menses are irregular, and then 30 days following the last dose of lenalidomide; women of childbearing potential must either commit to continued abstinence from heterosexual intercourse or begin two acceptable methods of birth control - one highly effective method (intrauterine device [IUD], hormonal, tubal ligation, or partner's vasectomy), and one additional effective method (latex condom, diaphragm, or cervical cap) - at the same time, at least 4 weeks before she begins lenalidomide therapy; "women of childbearing" potential is defined as a sexually mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months; men must agree not to father a child and must use a latex condom during any sexual contact with women of childbearing potential while taking lenalidomide and for 4 weeks after therapy is stopped, even if they have undergone a successful vasectomy
Absolute neutrophil count (ANC) >= 1000/uL
Platelets >= 100,000/uL
Creatinine clearance* >= 40 cc/min
- To be calculated by method of Cockcroft-Gault or after 24-hour urine collection
Creatinine =< 2 mg/dL
Total bilirubin =< 2 mg/dL
Aspartate aminotransferase (AST) =< 3 x upper limits of normal
Alkaline phosphatase =< 3 x upper limits of normal
Urine (U)-human chorionic gonadotropin (HCG) or serum HCG negative (if patient of childbearing potential)

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (melphalan, autologous PBSCT, lenalidomide)	Laboratory Biomarker Analysis	Beginning between day 100-110, patients receive lenalidomide PO once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.
Arm I (melphalan, autologous PBSCT, lenalidomide)	Autologous Hematopoietic Stem Cell Transplantation	Beginning between day 100-110, patients receive lenalidomide PO once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.
Arm I (melphalan, autologous PBSCT, lenalidomide)	Peripheral Blood Stem Cell Transplantation	Beginning between day 100-110, patients receive lenalidomide PO once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.
Arm II (melphalan, autologous PBSCT, placebo)	Autologous Hematopoietic Stem Cell Transplantation	Beginning between day 100-110, patients receive placebo PO once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.
Arm II (melphalan, autologous PBSCT, placebo)	Laboratory Biomarker Analysis	Beginning between day 100-110, patients receive placebo PO once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.
Arm I (melphalan, autologous PBSCT, lenalidomide)	Melphalan	Beginning between day 100-110, patients receive lenalidomide PO once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.
Arm II (melphalan, autologous PBSCT, placebo)	Peripheral Blood Stem Cell Transplantation	Beginning between day 100-110, patients receive placebo PO once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.
Arm II (melphalan, autologous PBSCT, placebo)	Placebo Administration	Beginning between day 100-110, patients receive placebo PO once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.
Arm I (melphalan, autologous PBSCT, lenalidomide)	Lenalidomide	Beginning between day 100-110, patients receive lenalidomide PO once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.
Arm II (melphalan, autologous PBSCT, placebo)	Melphalan	Beginning between day 100-110, patients receive placebo PO once daily. Treatment continues in the absence of disease progression or unacceptable toxicity.

Primary Outcome Measures

Name	Time	Method
Time to Progression	Duration of study (up to 10years)	Time to progression (TTP) was defined as the date of transplant to date of progression or death due to any cause, whichever occurs first. TTP was estimated using the Kaplan Meier method. Progression was defined per the International Myeloma Working Group definition as one more of the following: * 25% increase in serum M-component (absolute increase \>= 0.5g/dl) * 25% increase in urine M-component (absolute increase \>= 200mg/24hour * 25% increase in the difference between involved and uninvolved Free Light Chain levels (absolute increase \>= 10mg/dl) * 25 % increase in bone marrow plasma cell percentage (absolute increase of \>=10%) * Definite development of new bone lesion or soft tissue plasmacytomas * Development of hypercalcemia

Secondary Outcome Measures

Name	Time	Method
Response to Autologous Hematopoietic Stem-cell Transplant (HSCT) at Day 100	Day 100	Response was defined according to International Myeloma Working Group criteria (2006) * Complete Response: Complete disappearance of M-protein from serum \& urine on immunofixation, normalization of Free Light Chain (FLC) ratio \& \<5% plasma cells in bone marrow (BM) * Partial Response: \>= 50% reduction in serum M-Component and/or Urine M-Component \>= 90% reduction or \<200 mg per 24 hours; or \>= 50% decrease in difference between involved and uninvolved FLC levels * Marginal Response: 25-49% reduction in serum M-component \& urine M-component by 50-89% which still exceeds 200mg/24hour * Progressive Disease: Defined in primary outcome measure * Stable Disease: Not meeting any of the criteria above

Trial Locations

Locations (140): Mayo Clinic in Arizona
🇺🇸
Scottsdale, Arizona, United States
City of Hope Comprehensive Cancer Center
🇺🇸
Duarte, California, United States
University of California Davis Comprehensive Cancer Center
🇺🇸
Sacramento, California, United States
UC San Diego Medical Center - Hillcrest
🇺🇸
San Diego, California, United States
UCSF Medical Center-Mount Zion
🇺🇸
San Francisco, California, United States
The Medical Center of Aurora
🇺🇸
Aurora, Colorado, United States
Boulder Community Foothills Hospital
🇺🇸
Boulder, Colorado, United States
Penrose-Saint Francis Healthcare
🇺🇸
Colorado Springs, Colorado, United States
AdventHealth Porter
🇺🇸
Denver, Colorado, United States
Presbyterian - Saint Lukes Medical Center - Health One
🇺🇸
Denver, Colorado, United States
Scroll for more (130 remaining)
Mayo Clinic in Arizona
🇺🇸Scottsdale, Arizona, United States