Phase II Study of Dexamethasone, Thalidomide and Lenalidomide for Subjects With Relapsed or Refractory Multiple Myeloma

NCT00538824 | Terminated Phase 2 Results

• 2 other identifiers: 0708009381RV-MM-PI-0132
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Study Objectives

1. 1.To evaluate the efficacy of the combination of dexamethasone (Decadron®), thalidomide (Thalomid®), and lenalidomide (Revlimid®) as therapy for patients with relapsed or refractory multiple myeloma (MM) who have failed prior treatment with both lenalidomide and thalidomide when used as monotherapies.
2. 2.To evaluate the safety of the combination of lenalidomide, dexamethasone, and thalidomide as a therapy for patients with relapsed or refractory multiple myeloma.

Conditions

Multiple Myeloma

Keywords

myeloma; relapsed or refractory multiple myeloma

Outcome Measures

Primary Outcomes (1)

• Effect of Drug Combination on Multiple Myeloma

  The maximum response for all patients that were treated on study. Maximum response was assessed using the International myeloma working group (IMWG) guidelines for response. http://imwg.myeloma.org/international-myeloma-working-group-imwg-uniform-response-criteria-for-multiple-myeloma/

  The best response for all patients at any point were assessed for patients that were treated on study, from start of treatment up to 20 weeks

Study Arms (1)

DexTR (all patients)

EXPERIMENTAL

All patients were treated with the DexTR (dexamethasone / thalidomide, lenalidomide (Revlimid®)), which consisted of lenalidomide 25mg/day during days 1-21, dexamethasone 40mg/day on days 1-4, 9-12, and 17-20, and thalidomide 50mg/day for the first 7 days, followed by 100mg/day for all subsequent days, for a total of 4 cycles of 28 days each.

Drug: dexamethasone; Drug: thalidomide; Drug: lenalidomide

Interventions

dexamethasone DRUG

Cycles 1-4 • Dexamethasone (40mg ) will be given on days 1-4, 9-12, 17-20 of a 28-day cycle. After completing 4 cycles: * Patients who demonstrate disease progression at any time will be taken off study. * Patients who achieve a resolution of monoclonal gammopathy as detected on serum immunofixation or achieve a plateau of disease (no change in M-spike as detected on serum protein electrophoresis) for \> 2 cycles will be transitioned to maintenance therapy. * Patients who continue to respond without achieving either a plateau or a CR will continue on induction therapy until plateau for \>2 cycles or CR in the absence of untoward toxicity. These patients will be then transitioned to maintenance therapy. Maintenance therapy will consist of: • Dexamethasone 20mg weekly days 1, 8, 15, 22 out of a 28 day cycle)

DexTR (all patients)

thalidomide DRUG

Cycles 1-4 • Thalidomide will be given 50mg daily on days 1-7, thereafter 100mg daily on days 8-28 of the first 28-day cycle. Thalidomide will then be given at 100mg/daily for days 1-28 of each subsequent cycle. After completing 4 cycles: * Patients who demonstrate disease progression at any time will be taken off study. * Patients who achieve a resolution of monoclonal gammopathy as detected on serum immunofixation or achieve a plateau of disease (no change in M-spike as detected on serum protein electrophoresis) for \> 2 cycles will be transitioned to maintenance therapy. * Patients who continue to respond without achieving either a plateau or a CR will continue on induction therapy until plateau for \>2 cycles or CR in the absence of untoward toxicity. These patients will be then transitioned to maintenance therapy.

DexTR (all patients)

lenalidomide DRUG

Cycles 1-4 • Lenalidomide will be given 25mg daily for days 1-21 of each 28 day cycle. After completing 4 cycles: * Patients who demonstrate disease progression at any time will be taken off study. * Patients who achieve a resolution of monoclonal gammopathy as detected on serum immunofixation or achieve a plateau of disease (no change in M-spike as detected on serum protein electrophoresis) for \> 2 cycles will be transitioned to maintenance therapy. * Patients who continue to respond without achieving either a plateau or a CR will continue on induction therapy until plateau for \>2 cycles or CR in the absence of untoward toxicity. These patients will be then transitioned to maintenance therapy. Maintenance therapy will consist of: • Lenalidomide 25 mg/daily days 1 - 21 out of a 28 day cycle. 15mg/daily on days 1-21 of a 28 day cycle of lenalidomide will be given to patients with a creatinine clearance of \< 40cc/min\*

DexTR (all patients)

Eligibility Criteria

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

You may qualify if:

• Subject must voluntarily sign and understand written informed consent.
• Age \> 18 years at the time of signing the consent form.
• Histologically confirmed Salmon-Durie stage II or III MM. Stage I MM patients will be eligible if they display poor prognostic factors (ß2M ≥5.5 mg/L, plasma cell proliferation index ≥5%, albumin of less then 3.0, and unfavorable cytogenetics).
• Relapsed or refractory myeloma as defined by Appendix II, table 1, progression of disease either after prior therapy or lack of response to currently used therapy.
• Prior treatment with prior lenalidomide and thalidomide as single agents or in combination with dexamethasone, but not in combination with each other.
• No anti-myeloma therapy within 14 days prior to initiation of study treatment. Patients may be receiving adjuvant antiresorptive therapy (i.e., pamidronate or zoledronic acid) as routine care.
• Measurable disease as defined by \> 1.0 g/dL serum monoclonal protein, \>0.1 g/dL serum free light chains, \>0.2 g/24 hrs urinary M-protein excretion, and/or measurable plasmacytoma(s).
• Karnofsky performance status ≥70% (\>60% if due to bony involvement of myeloma.
• All study participants must be registered into the mandatory RevAssist® and S.T.E.P.S.® programs, and be willing and able to comply with the requirements of the RevAssist® and S.T.E.P.S.® programs.
• Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide and thalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy.
• Able to take aspirin daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).
• Life expectancy ≥ 3 months
• Subjects must meet the following laboratory parameters:
• Absolute neutrophil count (ANC) ≥1000 cells/mm3 (1.0 x 109/L)
• Platelets count ≥ 75,000/mm3 (75 x 109/L)

You may not qualify if:

• Patients with non-secretory MM (no measurable monoclonal protein, free light chains, and/or M-spike in blood or urine).
• Prior history of other malignancies (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless disease free for ≥ 5 years.
• Myocardial infarction within 6 months prior to enrollment , or NYHA(New York Hospital Association) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• Pregnant or lactating females are ineligible.
• Given the potential of the study drugs to trigger or worsen HIV viremia and the incidence of opportunistic infections inpatients infected with the HIV virus, HIV-1 or HIV-2 positive patients will be excluded. The interactions of HAART with study drugs have not been determined.
• Active hepatitis B or hepatitis C infection.
• Active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program.
• Any coexisting medical problem or laboratory evaluation that, in the treating physician's or principal investigator's opinion, makes the patient unsuitable to participate in this clinical trial.
• Known hypersensitivity to dexamethasone, lenalidomide, or thalidomide.
• History of thromboembolic event within the past 6 months prior to enrollment.

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Celgene: collaborator

Study Sites (1)

Weill Medical College of Cornell University

New York, New York, 10021, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell; Recurrence

Interventions

Dexamethasone; Thalidomide; Lenalidomide

Condition Hierarchy (Ancestors)

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; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; 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

Limitations and Caveats

The study was terminated early due to lack of sufficient accrual

Results Point of Contact

• Title: Jennifer Hess
• Organization: Weill Cornell Medical College

jmh2004@med.cornell.edu

6469629440

Study Officials

• Ruben Niesvizky, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2007
• First Posted: October 3, 2007
• Study Start: December 1, 2007
• Primary Completion: September 22, 2010
• Study Completion: September 22, 2010
• Last Updated: June 6, 2018
• Results First Posted: June 8, 2017

Record last verified: 2018-05

Locations

US (1)