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Tandem High-Dose Therapy With Melphalan and Total Marrow Irradiation (TMI) With Peripheral Blood Progenitor Cell Support and Lenalidomide Maintenance in Multiple Myeloma: A Phase I/II Trial


Phase 1/Phase 2
N/A
70 Years
Open (Enrolling)
Both
Refractory Multiple Myeloma, Smoldering Multiple Myeloma, Stage I Multiple Myeloma, Stage II Multiple Myeloma, Stage III Multiple Myeloma

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Trial Information

Tandem High-Dose Therapy With Melphalan and Total Marrow Irradiation (TMI) With Peripheral Blood Progenitor Cell Support and Lenalidomide Maintenance in Multiple Myeloma: A Phase I/II Trial


PRIMARY OBJECTIVES:

I. To assess the feasibility and toxicities of tandem cycle ablative therapy consisting
first of high-dose melphalan and then escalating doses of fractionated total marrow
irradiation (TMI) using helical tomotherapy in patients with advanced multiple myeloma.

II. To establish the maximum tolerated dose of TMI using helical tomotherapy. III. To assess
response rate, progression free and over-all survival following treatment with tandem cycle
ablative therapy consisting first of high-dose melphalan and then escalating doses of TMI
using helical tomotherapy with Dexamethasone/Thalidomide maintenance therapy in patients
with advanced multiple myeloma.

IV. To assess the feasibility of adding decadron and thalidomide as maintenance following
the second cycle of high-dose therapy.

SECONDARY OBJECTIVES:

I. To perform cytogenetic, gene rearrangement, and fluorescence in situ hybridization (FISH)
studies on baseline and post-treatment bone marrow and blood specimens and correlate the
presence/persistence of these features with treatment outcome.

II. To bank/develop cell lines developed for future investigations of tumor biology, and for
potential assessment of efficacy of novel therapeutic agents.

OUTLINE: This is a dose-escalation study of total marrow irradiation (TMI).

PRIMING AND APHERESIS: Patients receive cyclophosphamide IV over 2 hours. Patients also
receive filgrastim IV or subcutaneously daily beginning 24 hours after the administration
of cyclophosphamide and continuing until apheresis is complete. Patients undergo apheresis
until an adequate number of peripheral blood stem cells are collected.

ABLATIVE THERAPY:

Course 1: Patients receive high-dose melphalan IV over 30 minutes on days -2 and -1.
Patients then undergo autologous PBSC transplantation on day 0 and receive filgrastim IV or
subcutaneously beginning on day 5 and continuing until blood counts recover.

Course 2: Beginning 6-18 weeks later, patients undergo TMI once or twice daily on days -4 to
-1. Patients then undergo autologous peripheral blood stem cell transplant and receive
filgrastim IV or subcutaneously beginning on day 5 and continuing until blood counts
recover.

MAINTENANCE THERAPY: Beginning within 6-8 weeks of day 0 of course 2 (TMI), patients receive
oral lenalidomide daily. Courses repeat every 28 days for approximately 3 years in the
absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed at 30 days, every 6 months for 1
year, and then annually for at least 2 years.

Inclusion 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

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Feasibility

Outcome Time Frame:

At 3 years

Safety Issue:

No

Principal Investigator

George Somlo

Investigator Role:

Principal Investigator

Investigator Affiliation:

City of Hope Medical Center

Authority:

United States: Institutional Review Board

Study ID:

City of Hope 04064

NCT ID:

NCT00112827

Start Date:

November 2004

Completion Date:

Related Keywords:

  • Refractory Multiple Myeloma
  • Smoldering Multiple Myeloma
  • Stage I Multiple Myeloma
  • Stage II Multiple Myeloma
  • Stage III Multiple Myeloma
  • Multiple Myeloma
  • Neoplasms, Plasma Cell

Name

Location

City of Hope Medical CenterDuarte, California  91010