Multiple Myeloma Research Center

Home Research Education Resources Support Group

 

Arsenic in Myeloma Doxil in MM Therapy DVd with Revimid Revimid Therapy DVd T Neovastat PhaseII Osteoprotegerin(OPG) Rituxan Temodar Velcade Procrit IL-2 ATRA GM-CSF in MM Peg L-Asparaginase GM-CSF

Doxil, Vincristine,  Decadron and Revimid (DVd-R); A Phase I/II for  Relapsed/Refractory Multiple Myeloma

STUDY OBJECTIVES:

Primary: 

To identify the maximum tolerated dose (MTD) of CC-5013 [Revimid™ (R)] in combination with Doxil®, vincristine and dexamethasone (DVd) as treatment for subjects with relapsed or refractory multiple myeloma (MM).

 Secondary: 

To evaluate the overall safety of CC-5013 [Revimid™] when combined with DVd as treatment for subjects with relapsed or refractory MM.

To evaluate the preliminary efficacy of CC-5013 [Revimid™] when combined with DVd

To evaluate the effect of combination DVd-R on biological markers, coagulation parameters and myeloma paraprotein levels

STUDY DESIGN: 

This is a single-center, single-arm, open-label study of CC-5013 [Revimid™ (R)]) plus Doxil®, vincristine, and dexamethasone (DVd). The study will be a standard dose-escalation study to determine the MTD within the first 35 days of therapy with CC-5013 in combination with fixed doses of Doxil 40® mg / m2 IVPB Day 1, vincristine 2.0 mg IVP Day 1 and dexamethasone 40 mg PO daily days 1 - 4.  A maximum enrollment of 40 subjects is anticipated for this study.

 Study Phases

 Maximal Tolerated Dose (MTD) Phase

Subjects will be screened within 28 days of baseline as outlined in Section 2 Schedule of Study Assessments. Subjects meeting all inclusion/exclusion criteria will be enrolled in cohorts of 3-6 to receive CC-5013 in combination with DVd in a 35-day cycle. Five dose groups are planned. For each subject in the MTD phase, Cycle 1 CC-5013 will be started on Day 1 and the initiation of DVd will be delayed until Day 8 to facilitate the drawing biological blood studies while the subject is taking only CC-5013.  The resulting length of Cycle 1 is 35 days instead of 28 days.

During the MTD phase, a dose-limiting toxicity (DLT) is defined as a grade 3 or greater non-hematological toxicity or grade 4 hematological toxicity using Appendix VIII: . The study will follow a sequential dose-escalation, “3 + 3” design. Initially, three subjects will be started on treatment with dose regimen 1 as defined in Section 7.5 Treatments. After the third subject completes 35 days of treatment, if no dose-limiting toxicity occurs, then the next group of 3 subjects will be treated at the next higher dose regimen. If 1 of the 3 initial subjects experiences a DLT, the cohort of subjects will be expanded to 6 subjects.  If fewer than two DLTs occur in 6 subjects, then the next higher dose group will be initiated.  If 2 or more (of a cohort of up to 6) subjects experience DLT, no further dose escalations will occur and the MTD will have been exceeded.  A similar approach will be followed for each dose escalation. Serial measurements of safety during the MTD phase will be performed at each visit as outlined in Section 2: Schedule of Study Assessments. Ten additional subjects will be enrolled at the MTD.

Extension Phase

Subjects who complete the MTD phase of the study without evidence of disease progression may continue on DVd-R, until disease progression is confirmed or study drug is discontinued for any reason. During the extension phase, the subject may continue to receive a maximum of 5 additional 28-day cycles of their assigned DVd-R dose. Subjects with evidence of progression at any visit will be discontinued from the study. Subjects with at least stable disease may continue in the extension phase until “best response” is determined (Appendix II: SWOG Response Definitions). Upon the determination of “best response”, 2 additional cycles of DVd-R will be administered (a maximum of 6 cycles of DVd-R may be administered). Serial measurements of safety and efficacy during the extension phase will be performed at each visit as outlined in Section 2: Schedule of Study Assessments. Subjects will continue on DVd-R as defined above or until disease progression is confirmed or study drug, CC-5013, is discontinued for another reason.

 

STUDY ENDPOINTS

Primary: 

Safety  (type, frequency, severity, and relationship of adverse events to DVd-R).

Secondary:

Myeloma paraprotein response

Correlation of exploratory biological and coagulation studies with myeloma paraprotein response

 

STUDY DURATION:

 Study drug treatment continues for a maximum of 6 cycles, until lack of therapeutic effect is documented, or study drug, C-5013, is discontinued for any reason.

 STUDY POPULATION

Inclusion Criteria:

  1. Understand and voluntarily sign an informed consent form.
  2. Age >18 years at the time of signing the informed consent form.
  3. Able to adhere to the study visit schedule and other protocol requirements.
  4. Diagnosed with active multiple myeloma (see Appendix I: Criteria for Diagnosis of Multiple Myeloma & Clinical Myeloma Staging System) and be considered to have disease progression after at least 2 cycles of anti-myeloma treatment or have relapsed with progressive disease after treatment (see Appendix II for the definitions of disease progression and relapsed and refractory multiple myeloma).
  5. Measurable myeloma paraprotein levels in serum (≥ 0.5g/dL) or urine (≥ 0.2 g excreted in a 24-hour collection sample).
  6. Eastern Cooperative Group (ECOG) Performance Status of 0-2 (see Appendix V: ECOG Performance Status Scale). Performance status of 3 and 4 will be allowed if related to bony disease.
  7. Bilirubin < 2 x upper limits of normal (ULN).
  8. Liver enzymes (ALT or AST) < 3 x ULN.
  9. Must have adequate bone marrow function: 
    1. Absolute neutrophil count > 1,000 cells/mm3 (1.0 x 109/L)
    2. Platelets > 100,000 cells/mm3 (100 x 109/L)
    3. Hemoglobin > 8 g/dL
  10. Must have adequate renal function:  creatinine < 2.5 mg/dL.
  11. Must have 2-d echocardiogram indicating LVEF > 50% within 42 days prior to first dose of study drug. 
  12. Women of childbearing potential (WCBP)† must have a negative serum or urine pregnancy test within 7 days of starting study drug.  In addition, sexually active WCBP must agree to use adequate contraceptive methods (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) while on study drug. WCBP must agree to have pregnancy tests every 4 weeks while on study drug.

Exclusion Criteria:

  1. Severe infection requiring intravenous antibiotic treatment.
  2. Life expectancy of less than 3 months.
  3. Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in-situ cervical cancer, or other cancer from which the subject has been disease-free for at least 5 years.
  4. Solitary bone or solitary extramedullary plasmacytoma as the only evidence of plasma cell dyscrasia.
  5. Subjects who have received > 500mg/m2 of doxorubicin alone, or Doxil® alone, or doxorubicin plus Doxil®.
  6. Prior treatment with CC-5013.
  7. Prior development of > grade 2 (NCI CTC) allergic reaction/hypersensitivity while taking thalidomide.
  8. Prior development of a > grade 3 (NCI CTC) rash or any desquamation while taking thalidomide.
  9. History of cardiac disease, with New York Heart Association Class II or greater (see Appendix VII: New York Heart Association (NYHA) Classification).
  10. Uncontrolled medical problems such as diabetes mellitus, coronary artery disease, hypertension, unstable angina, arrhythmias), pulmonary, hepatic and renal diseases unless renal insufficiency is felt to be secondary to multiple myeloma.
  11. Any investigational agent or systemic anti-myeloma therapy within 28 days of the first dose of treatment.
  12. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
  13. Pregnant or lactating females.
  14. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. 
 
Home Up
Phone: 216-445-6830
Fax: 216-445-3434

Maps & Directions

 Cleveland Clinic Home  |   Contact Us  |   Disclaimer  |   Privacy Statement
© Cleveland Clinic 2005

Page Last Updated 09/02/2003 03:09:17 PM