Melphalan and Radiation Therapy Followed By Lenalidomide in Treating Patients Who Are Undergoing Autologous Stem Cell Transplant for Stage I, Stage II, or Stage III Multiple Myeloma

• Status: Completed
• Trial end date: 2019-02-15
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Melphalan, a chemotherapeutic agent, has been found to be an effective treatment choice for destroying myeloma cells, especially when given at high (bone marrow ablative) doses. Total marrow irradiation (TMI)/ablative dose radiation therapy is another modality capable of destroying myeloma cells. Autologous peripheral blood/stem cell transplant (ASCT) given after either melphalan or following TMI (aimed at the bone marrow containing areas of the skeleton, the site of origin of myeloma cells) will shorten the duration/alleviate the severity of both melphalan and marrow irradiation-associated side effects. Lenalidomide, an effective agent on its own right for the treatment of myeloma, has been shown to further enhance the beneficial effects of autologous stem cell transplants when given as maintenance therapy.

PURPOSE: This previously phase I trial established the maximum tolerated dose of TMI at 1600 cGy. The phase II part of this study is ongoing and is studying the effects of high-dose melphalan and ASCT, followed by TMI and a second ASCT, with subsequent maintenance lenalidomide. The study is conducted in patients with stages I-III myeloma, with specific emphasis on assessing complete and very good partial response rate conversions, progression-free and overall survival, and safety/feasibility of delivering the planned treatment regimen.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: City of Hope Medical Center
• Treatments: Cyclophosphamide; Lenalidomide; Lenograstim; Melphalan; Sargramostim; Thalidomide

Criteria

Criteria

• Patients with multiple myeloma (stages I-III) will be eligible if they are either in response, or have stable disease

• Patients with smoldering myeloma are eligible if there is evidence of progressive disease requiring therapy (>= 25% increase in M protein levels or Bence Jones excretion; Hgb =< 10.5 g/dl; frequent infections; hypercalcemia; rise in serum creatinine above normal on two separate occasion)

• Patients with non-quantifiable monoclonal proteins are eligible provided they meet other criteria for multiple myeloma, or smoldering myeloma, and they have evaluable or measurable disease by other (radiographic) means

• Unlimited prior chemotherapy regimens allowed

• KPS >= 70%

• Patients with Waldenstrom's macroglobulinemia are not eligible

• Less than 18 months since diagnosis

• No contraindication to the collection of a minimum of 4 x 10^6 CD34+ cells/kg by apheresis

• All patients must have signed a voluntary, informed consent in accordance with institutional and federal guidelines

• Adequate hepatic function as demonstrated by bilirubin, =< 1.5 mg/dl, and SGOT and SGPT < 2.5 x upper limits of normal

• Adequate renal function as demonstrated by: creatinine of measured or calculated creatinine clearance of > 50 cc/min

• Absolute neutrophil count of > 1000/ul, platelet count of > 100,000/ul

• Cardiac ejection fraction >= 50% by MUGA scan and/or by echocardiogram

• Adequate pulmonary function as demonstrated by FEV1 > 60% and DLCO > 50% of predicted lower limit

• Hepatitis B antigen, Hepatitis C RNA and HIV antibody tests negative

• No other medical, or psychosocial problems, which in the opinion of the primary physician or principal investigator would place the patient at unacceptably high risk from this treatment regimen

• Females of reproductive age not using adequate birth control measures/ or who are pregnant are not eligible

• History of other malignancies within the last 3 years, as long as patients have remained in complete remission for at least 2 years, except for non-melanoma skin cancer and in situ carcinoma of the cervix

• Patients should have finished their prior chemotherapy at least 14 days prior to cyclophosphamide priming, and should have received their last dose of thalidomide, dexamethasone, or bisphosphonate > 10 days prior to cyclophosphamide priming

• Pre-treatment tests must have been performed within 6 weeks prior to initiation of cyclophosphamide; A CBC, platelet count and comprehensive chemistry panel should be performed within 1 week prior to initiating cyclophosphamide priming

• Known hypersensitivity to Filgrastim or to E. coli derived proteins is an exclusion

• Inability to lie supine in a full body cast for approximately 30 minutes, the anticipated duration of each treatment session, is an exclusion

• Previous radiation therapy to more than 20% of bone marrow containing areas, or to any area exceeding 2000 cGy, is an exclusion

• Patients must be fully aware of the teratogenic potential of thalidomide and agree to fully comply with the mandated guidelines regarding contraception as stated in the informed consent and the patient warning document attached to the consent form

• Women of childbearing potential must have a negative pregnancy test performed within 24 hours prior to beginning thalidomide, except for woman who have been postmenopausal for at least 2 years, or underwent hysterectomy

• Use of effective means of contraceptive should be started at least 2 weeks prior to initiating thalidomide