Basic Trial Information
Trial Description
     Summary
     Eligibility Criteria
Trial Contact Information

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Active	18 and over	Pharmaceutical / Industry	C05008 NCT00507442

Trial Description

Summary

The purpose of this Phase 1/2 study is to evaluate the efficacy and safety of treatment with VELCADE, dexamethasone, and Revlimid® (VDR) as well as VELCADE, dexamethasone, cyclophosphamide, and Revlimid (VDCR) in patients with multiple myeloma who have received no prior treatment. This study will evaluate whether the addition of Revlimid to VELCADE and Dexamethasone will increase the CR/ very good partial response (VGPR) rate.

Eligibility Criteria

Inclusion Criteria:

1. Voluntary written informed consent must be given before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

2. Male or female subject 18 years of age or older

3. A Karnofsky Performance Status score of ≥50% (Eastern Cooperative Oncology Group Performance Status score ≤2)

4. Subjects must have symptomatic myeloma or asymptomatic myeloma with myeloma-related organ damage

5. Multiple myeloma diagnosed according to the following standard criteria:

Major criteria

• 1. Plasmacytomas on tissue biopsy

• 2. Bone marrow plasmacytosis (>30% plasma cells)

• 3. Monoclonal immunoglobulin spike on SPEP, immunoglobulin G (IgG) >3.5 g/dL or immunoglobulin A (IgA) >2.0 g/dL; kappa or lambda light chain excretion >1 g/day on 24-hour urine protein electrophoresis (UPEP)

Minor criteria

• a. Bone marrow plasmacytosis (10% to 30% plasma cells)

• b. Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria

• c. Lytic bone lesions

• d. Normal IgM (<50 mg/dL), IgA (<100 mg/dL), or IgG (<600 mg/dL)

Any of the following sets of criteria will confirm the diagnosis of multiple myeloma

• Any 2 of the major criteria

• Major criterion 1 plus minor criteria b, c, or d

• Major criterion 3 plus minor criteria a or c

• Minor criteria a, b, and c or a, b, and d.

6. Subjects must have measurable disease requiring systemic therapy. Measurable disease is defined by at least 1 of the following 3 measurements:

• Serum M-protein ≥1 g/dL (≥10 g/L)

• Urine M-protein ≥200 mg/24 hours

• Serum free light chain assay: involved free light chain level ≥10 mg/dL (≥100 mg/L) provided the serum free light chain ratio is abnormal

7. Subjects must not have been treated previously with any systemic therapy for multiple myeloma. Prior treatment with corticosteroids or radiation therapy does not disqualify the subject (the maximum dose of corticosteroids should not exceed the equivalent of 160 mg of dexamethasone1 in a 2-week period).

8. Two weeks must have elapsed since the date of the last radiotherapy treatment. Enrollment of subjects who require concurrent radiotherapy (which must be localized in its field size) should be deferred until the radiotherapy is completed and 2 weeks have elapsed since the last date of therapy.

9. Women of childbearing potential must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 to 14 days prior to therapy and repeated within 24 hours before starting study drug. They must commit to continued abstinence from heterosexual intercourse or begin 2 acceptable methods of birth control (1 highly effective method and 1 additional effective method) used at the same time, beginning at least 4 weeks before initiation of Revlimid treatment. Women must also agree to ongoing pregnancy testing. (See section 7.4.8.1 for further details regarding the frequency of pregnancy testing and acceptable methods of birth control.)

10. Men must agree to not father a child and agree to use a latex condom during therapy and for 4 weeks after the last dose of study drug, even if they have had a successful vasectomy, if their partner is of childbearing potential.

11. All subjects must agree to comply with the requirements of the RevAssistSM program.

Exclusion Criteria:

1. History of allergy to any of the study medications, their analogues, or excipients in the various formulations

2. ≥Grade 2 peripheral neuropathy on clinical examination

3. Serum creatinine ≥2.5 mg/dL

4. Absolute neutrophil count (ANC)<1000 per µL

5. Platelet count <70,000 per µL

6. Aspartate transaminase (AST [SGOT]) and alanine transaminase (ALT [SGPT]) >2 × the upper limit of normal (ULN)

7. Total bilirubin >3 × ULN

8. Myocardial infarction within 6 months prior to enrollment or New York Heart Association Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or clinically significant conduction system abnormalities.

9. Female subject who is pregnant or breast-feeding

10. Clinically relevant active infection or serious comorbid medical conditions

11. Any condition, including laboratory abnormalities, that in the opinion of the Investigator places the subject at unacceptable risk if he/she were to participate in the study. This includes but is not limited to serious medical or psychiatric illness likely to interfere with participation in this clinical study.

12. Active prior malignancy diagnosed or treated within the last 3 years

Trial Contact Information

Trial Lead Organizations/Sponsors

Millennium Pharmaceuticals, Incorporated

Christine Colby, Pharm.D.		Ph: 1-866-835-2233
		Email: medical@mlnm.com

U.S.A.
Minnesota
	Rochester
	Mayo Clinic Cancer Center

Link to the current ClinicalTrials.gov record.
NLM Identifer NCT00507442
Information obtained from ClinicalTrials.gov on March 18, 2009