Evaluation of Lenalidomide, Doxorubicin and Dexamethasone (RAD) in Patients With Relapsed or Refractory Multiple Myeloma

NCT00306813 | Completed Phase 1

• 1 other identifier: DSMM VII
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multi-center, open label, uncontrolled, non-comparative phase I/II study in patients with refractory or relapsed multiple myeloma who are eligible for second, third, or fourth line therapy. Patients will be enrolled sequentially into four dose cohorts. The feasibility of administrating Revlimid (R) in combination with Doxorubicin and Dexamethasone (AD) and the MTD of the combination will be determined in the phase I part of the study (Part A). When the MTD has been established, the efficacy of the combination will be further evaluated in the phase II part of the study Part B)

Conditions

Relapse; Refractory Multiple Myeloma

Keywords

refractory or relapsed multiple myeloma; CC-5013; Revlimid; lenalidomide; RAD

Outcome Measures

Primary Outcomes (6)

• Part A (phase I)

• To determine the safety and maximum tolerated dose (MTD) of

• Revlimid in combination with Doxorubicin and Dexamethasone

• (RAD) administered as a VAD-like regimen in subjects with relapsed or refractory multiple myeloma.

• Part B (Phase II):

• To determine the efficacy of RAD as treatment for subjects with relapsed or refractory multiple myeloma by estimating the objective response rate (PR, RR and CR).

Secondary Outcomes (4)

• Secondary objectives of the study are:

• Part A plus Part B

• To determine the efficacy of RAD as treatment for subjects with relapsed or refractory multiple myeloma by estimating the objective response rate (PR, RR and CR).

• To estimate duration of response (PR, RR and CR) and disease control rate (SD, PR and CR).

Interventions

Revlimid DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Understand and voluntarily sign an informed consent form.
• Age \> 18 years at the time of signing the informed consent form.
• Multiple myeloma with Durie-Salmon stage II or III and considered to have disease progression after at least 1 previous anti-myeloma regimen (examples: induction chemotherapy followed by stem cell collection and high dose chemotherapy and autologous PBSCT; MP; anthracycline-containing regimen \> 3 months ago, any other conventional regimen including thalidomide- or bortezomib containing regimens.
• Subjects must have not have recieved more than 3 previous anti-myeloma regimens and must be relapsed or refractory following at least one regimen of anti-myeloma therapy.
• No anthracycline-containing regimen (e.g. VAD) within the last 3 months of study.
• Subjects may have been previously treated with thalidomide or bortezomib.
• Radiation therapy after start of the protocol will be considered as treatment failure except when given to treat pathological fractures or preexisting osteolytic lesions.
• Patients must have measurable levels of myeloma paraprotein in serum (\>0.5 g/dl) or urine (\>0.2 g excreted in a 24-hour collection sample).
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
• Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days of starting each cycle. Men and WCBP must agree to use adequate contraceptive methods.
• Must have a 2-d echocardiogram indicating LVEF ≥ 55% within 42 days prior to first dose of study drug.
• Life extpectancy \> 3 months.

You may not qualify if:

• The presence or any of the following will exclude a subject from study enrollment.
• Any serious medical condition, laboratory abnormality, or psychiatric illness that makes the patient ineligeble for the study. 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.
• Pregnant or lactating females.
• Heart failure (EF \< 55%).
• Any of the following laboratory abnormalities Absolute neutrophil count (ANC) \<1500/mm3 (1x109/L) Platelet count (PLT) \<100000/mm3 Serum creatinine\> 2.5 mg/dL SGOT and SGPT \> 3 x upper limit of normal (ULN) Serum total bilirubin \>1.2 mg/dL
• Prior history of any other malignancies except for adequately treated basal cell, insitu cervical or breast cancer or other for which the patient has been disease free for 5 years.
• Known hypersensitivity to thalidomide, dexamethasone and/or anthracyline.
• Prior use of Revlimid.
• Anthracycline-containing regimen (e.g. VAD) within the last 3 months of study.
• Any history of thrombembolic events
• Use of any standard or experimental anti-myeloma drug therapy within 28 days of study enrolment.
• Major surgery or radiotherapy within 4 weeks of study enrolment.
• Active infection requiring antibiotic therapy.
• Subjects who have received \> 300 mg/m2 lifetime cumulative dose of doxorubicin alone, or Doxil® alone, or doxorubicin plus Doxil®.
• History of cardiac disease, with New York Heart Association Class II or greater (See Appendix VII).

Sponsors & Collaborators

• University of Wuerzburg: lead

Study Sites (1)

Dept. of Internal Medicine II, University of Wuerzburg

Würzburg, Bavaria, 97070, Germany

Location

Related Publications (1)

• Knop S, Gerecke C, Liebisch P, Topp MS, Platzbecker U, Sezer O, Vollmuth C, Falk K, Glasmacher A, Maeder U, Einsele H, Bargou RC. Lenalidomide, adriamycin, and dexamethasone (RAD) in patients with relapsed and refractory multiple myeloma: a report from the German Myeloma Study Group DSMM (Deutsche Studiengruppe Multiples Myelom). Blood. 2009 Apr 30;113(18):4137-43. doi: 10.1182/blood-2008-10-184135. Epub 2009 Jan 30.

  PMID: 19182205 DERIVED

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Interventions

Lenalidomide

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Ralf Bargou, MD

  Dept. of Internal Medicine II, University of Wuerzburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: March 15, 2006
• First Posted: March 24, 2006
• Study Start: September 1, 2004
• Study Completion: December 1, 2008
• Last Updated: August 4, 2009

Record last verified: 2006-03

Locations

DE (1)