Third-line Therapy of Multiple Myeloma a Prospective Phase I /II Trial

NCT01010243 | Unknown Phase 1 DMC

• 1 other identifier: MM03
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 6

Brief Summary

To investigate the effect of an anti-inflammatory therapy consisting of lenalidomide in combination with pioglitazone, dexamethasone and metronomic low-dose chemotherapy with treosulfan on the response rate in patients with relapsed or refractory or progressive multiple myeloma(MM). Phase I: to determine the lenalidomide dse for the phase II part (5 mg or 10 mg or 15 mg) on the basis of dose-limiting toxicities (DLTs') in the first 4 weeks of treatment. Phase II: to determine

• response rate (primary objective)
• time to progression (TTP)
• time to partial response (TPR)
• overall survival (OS)
• quality of life
• tolerability and safety

Conditions

Multiple Myeloma

Keywords

multiple myeloma; anti-inflammatory; relapsed; refractory; progressive

Outcome Measures

Primary Outcomes (1)

• response rate

  2012

Secondary Outcomes (1)

• Time to progression

  2012

Interventions

Lenalidomide, Pioglitazone, dexamethasone, treosulfan DRUG

Phase I:lenalidomide dose ( 5 mg or 10 mg or 15 mg) will be determined for phase II on the basis of DLTs in the first 4 weeks for the phase II part. Start Phase I part: lenalidomide 10 mg p.o. daily + pioglitazone 60 mg p.o. daily + treosulfan 250 mg p.o. bid + dexamethasone initially 40 mg p.o. d1-4 and d15-18, then 20mg d1 and d15. dexamethasone 1 mg p.o. continuously within the intervals of pulsed dexamethasone therapy

Eligibility Criteria

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

You may qualify if:

• At least 18 years of age
• Must be able to adhere to the study visit schedule and other protocol requirements.
• Must be diagnosed with multiple myeloma that is progressing or has relapsed with progressive disease after at least two different anti-myeloma treatments (including lenalidomide in one schedule for phase II part only)
• In case of patients that have progressive disease after complete remission during preceding treatment: Serum monoclonal paraprotein (M-protein) level
• ≥0.5 g/dL for IgG, IgA myeloma and ≥0.05 g/dL for IgD myeloma or urine M-protein level ≥ 0.2 g excreted in a 24-hour collection sample or In case of progressive disease without complete remission during preceding treatment: \> 25% increase of serum monoclonal paraprotein or urine M-protein in comparison to the preceding monoclonal paraprotein (M-protein)nadir in serum /urine M-protein nadir in a 24 hour collection sample
• Sufficient bone marrow function: neutrophils ≥ 2x109/l, hemoglobin ≥10 g/dl, and platelets ≥ 100x109/l
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 (see Post Text Supplement 2).
• Subjects must discontinue all anti-myeloma drug or non-drug therapy prior to the first dose of study drug (at least 4 weeks).
• Required laboratory results:
• Liver function: Total bilirubin \< 1.5 times of upper limit of local institution (ULN), SGPT, SGOT ≤ 2.5 times of upper limit of local institution .
• Renal function: serum creatinine ≤ 1.5 ULN c)PT-INR/PT \<1.5 ULN
• Normal cardiac function
• Patients with prior thromboembolic event with adequate anticoagulation
• Life expectancy at least 3 months
• Written informed consent of the patient prior to screening procedures

You may not qualify if:

• Patients who require vitamin K antagonists except for low dose (INR ≤ 2,5)
• Known hypersensitivity to dexamethasone. Prior history of uncontrollable side effects to dexamethasone therapy.
• Active infection \> grade 2 NCI-CTC version 3.0
• Known diagnosis of HIV, hepatitis B, or hepatitis C infection.
• Severe, unstable, or uncontrolled medical disease which would confound diagnoses or evaluations required by the protocol, including cardiac insufficiency (NYHA I -IV) uncontrolled diabetes, chronic hepatic or renal disease, active uncontrolled infection and chronic inflammatory intestinal disease, autoimmune diseases.
• Prior radiation therapy \> 25% of bone marrow
• Regular blood transfusions
• Treatment with other experimental substances within 30 days before study start
• Participation in another clinical trial within 30 days before study start or during the trial
• Unwilling or unable to comply with the protocol
• Pregnant or lactating females.
• Patients with seizure disorders requiring medication (such as steroids or antiepileptics)
• Known hypersensitivity to one of the medications
• Patients with evidence or history of bleeding diathesis
• Patients undergoing renal dialysis

Sponsors & Collaborators

• University of Regensburg: lead
• ClinAssess GmbH: collaborator

Study Sites (6)

University of Regensburg

Regensburg, Germany, 93053, Germany

RECRUITING

Schön Klinik Starnberger See

Berg, 82335, Germany

RECRUITING

Gemeinschaftspraxis Dres. med. J. Wilke u. H. Wagner

Fürth, 90766, Germany

RECRUITING

Universitätsklinikum Schleswig-Holstein, II Medizin, Sekt. f. Stammzell- u. Immuntherapie

Kiel, 24105, Germany

RECRUITING

Klinikum d. Universität München, Med. Klinik u. Poliklinik IV, Abt. H/O

München, 80336, Germany

RECRUITING

Gemeinschaftspraxis Hämato/Onkologie

München, 81241, Germany

RECRUITING

MeSH Terms

Conditions

Multiple Myeloma; Recurrence

Interventions

Lenalidomide; Pioglitazone; Dexamethasone; treosulfan

Condition Hierarchy (Ancestors)

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

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; Thiazolidinediones; Thiazoles; Sulfur Compounds; Azoles; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Albrecht Reichle, Professor

  University of Regensburg

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Albrecht Reichle, Professor MD

CONTACT

+499419445540; albrecht.reichle@klinik.uni-regensburg.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor MD

Study Record Dates

• First Submitted: November 6, 2009
• First Posted: November 9, 2009
• Study Start: October 1, 2009
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2016
• Last Updated: May 30, 2012

Record last verified: 2012-05

Locations

DE (6)