Trial for Patients Not Qualifying for TT4 and TT5 Protocols Because of Prior Therapy

NCT00871013 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: 108053
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

There have been four previous Total Therapy (TT1 through IIIB) studies for multiple myeloma at the MIRT from 1989 to present. Results have shown that participants treated on these studies had better outcomes (meaning they have lived longer and had better responses to treatment) when compared to individuals treated with standard chemotherapy. Past studies conducted at the MIRT have shown that participants presenting to MIRT who have already received treatment for myeloma tend to have shorter remissions (disappearance of signs and symptoms of myeloma) and do not survive as long as participants who come to MIRT with untreated myeloma. Researchers at MIRT think that one reason for this is may be that the myeloma cells re-grow in the time when participants are not receiving treatment because they are recovering from high-dose chemotherapy. In this study, participants will receive several chemotherapy drugs previously shown to be effective in myeloma, but in lower doses and in shorter cycles. It is hoped that by giving the drugs in this way, myeloma cells will not have time to re-grow between cycles, therefore resulting in longer remissions. This study is being done in an attempt to improve the remission rate and the survival time for participants with high-risk myeloma.

Conditions

Myeloma

Keywords

improve remission rate & survival time in high-risk myeloma

Outcome Measures

Primary Outcomes (1)

• The primary objective of this study is to assess the continued complete and near complete response rate (CR/nCR) at two years after initiation of therapy. .

  Two years

Study Arms (1)

MEL-VTD-PACE

EXPERIMENTAL

Melphalan, Velcade, Thalidomide, Dexamethasone, CisPlatin, Adriamycin, Cyclophosphamide, Etoposide

Drug: Melphalan; Drug: Velcade; Drug: Thalidomide; Drug: Dexamethasone; Drug: Cisplatin; Drug: Adriamycin; Drug: Cyclophosphamide; Drug: Etoposide

Interventions

Melphalan DRUG

Given by vein, Day 3 First Inter-Therapy Treatment Bortezomib (Velcade) By vein Days 1 and 4 Second Inter-Therapy Treatment Bortezomib (Velcade) By vein Days 1 and 4 Second Transplant Bortezomib (Velcade) By vein Day -5 and Day -2 Year 1 Maintenance Velcade (bortezomib) By vein Days 1, 8, 15, 22(weekly) Every 28 days Years 2 \& 3 Maintenance Velcade (bortezomib) By vein Days 1, 8, 15, 22(weekly) Every 56 days

Also known as: Alkeran

MEL-VTD-PACE

Velcade DRUG

Given by vein, Days 1, 5, 8, 11

Also known as: Bortezomib, PS-341

MEL-VTD-PACE

Thalidomide DRUG

Given by mouth at bedtime, Days 5-8

Also known as: Thalomid

MEL-VTD-PACE

Dexamethasone DRUG

Given by mouth, once per day Days 5-8

Also known as: Decadron

MEL-VTD-PACE

Cisplatin DRUG

Given by vein, Days 5-8 continuous infusion

Also known as: Platinol, CDDP

MEL-VTD-PACE

Adriamycin DRUG

Given by vein, days 5-8 continuous infusion

Also known as: Doxorubicin

MEL-VTD-PACE

Cyclophosphamide DRUG

Given by vein days 5-8 continuous infusion

Also known as: Cytoxan

MEL-VTD-PACE

Etoposide DRUG

Given by vein days 5-8 continuous infusion

Also known as: Vepesid, VP-16

MEL-VTD-PACE

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with symptomatic multiple myeloma (MM), with at least one prior line of chemotherapy or newly diagnosed without any prior therapy.
• Zebroid ≤ 2, unless solely due to symptoms of MM-related bone disease (Appendix 4).
• Patients must be at least 18 years of age and not older than 75 years of age at the time of registration.
• Patient must not have had a prior auto- or allotransplant.
• Patient must have signed an IRB-approved informed consent and understand the investigational nature of the study.
• Patients must have adequate pulmonary function studies ≥ 50% of predicted on mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) ≥ 50% of predicted, within 60 days prior to enrollment. Patients unable to complete pulmonary function tests because of myeloma-related chest pain, must have a high resolution CT scan of the chest and must also have acceptable arterial blood gases defined as P02 greater than 70.
• Ejection fraction by ECHO or MUGA must be ≥ 40% and must be performed within 60 days prior to enrollment, unless the patient has received chemotherapy within that period of time (dexamethasone and thalidomide excluded), in which case the LVEF must be repeated.
• Patients must not have prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the patient has not received treatment for one year prior to enrollment. Other cancers will only be acceptable if the patient's life expectancy exceeds five years.
• Patients must be able to receive full doses of Mel-VRD-PACE, in the opinion of the treating investigator, with the exception that patients with creatinine clearance 30-50 ml/min will receive only 50% of the cisplatin dose.

You may not qualify if:

• Fever or active infection requiring intravenous antibiotic, defined as fever or antibiotics within 72 hours from registration.
• Severe renal dysfunction, defined as a creatinine \> 3mg/dl or a creatinine clearance of \< 30ml/min.
• Significant neurotoxicity, defined as grade ≥ 3 neurotoxicity per NCI Common Toxicity Criteria (See Appendix).
• Platelet count \< 30,000/mm3, and ANC \< 1,000/μl
• POEMS Syndrome: (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes
• Clinically significant hepatic dysfunction as noted by direct bilirubin or AST \>3 times the upper normal limit or clinically significant concurrent hepatitis.
• New York Heart Association (NYHA) Class III or Class IV heart failure (Appendix 4).
• Recent (≤ 6 months) myocardial infarction, unstable angina, difficult to control congestive heart failure, uncontrolled hypertension, or difficult to control cardiac arrhythmias are ineligible.
• Patients with a history of treatment for clinically significant ventricular cardiac arrhythmias.
• Poorly-controlled hypertension, diabetes mellitus, or other serious medical illness or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol.
• Prior cumulative total of Adriamycin exposure \>450 mg/m2.
• Prior exposure to thalidomide which resulted in severe toxicity requiring drug discontinuation.
• Prior exposure to Revlimid which resulted in severe toxicity requiring drug discontinuation
• Hypersensitivity to boron, or Mannitol. Prior exposure to bortezomib which resulted in severe toxicity requiring drug discontinuation.
• Pregnant or nursing women may not participate. Women of childbearing potential must have a negative pregnancy documented within one week of registration. Women/men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.

Sponsors & Collaborators

• University of Arkansas: lead

Study Sites (1)

University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

Location

Related Publications (1)

• Davies FE, Rosenthal A, Rasche L, Petty NM, McDonald JE, Ntambi JA, Steward DM, Panozzo SB, van Rhee F, Zangari M, Schinke CD, Thanendrarajan S, Walker B, Weinhold N, Barlogie B, Hoering A, Morgan GJ. Treatment to suppression of focal lesions on positron emission tomography-computed tomography is a therapeutic goal in newly diagnosed multiple myeloma. Haematologica. 2018 Jun;103(6):1047-1053. doi: 10.3324/haematol.2017.177139. Epub 2018 Mar 22.

  PMID: 29567784 DERIVED

Related Links

• Multiple Myeloma

MeSH Terms

Conditions

Neoplasms, Plasma Cell

Interventions

Melphalan; Bortezomib; Thalidomide; Dexamethasone; Calcium Dobesilate; Cisplatin; Doxorubicin; Cyclophosphamide; Etoposide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms

Intervention Hierarchy (Ancestors)

Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Chlorine Compounds; Nitrogen Compounds; Platinum Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides

Study Officials

• Maurizio Zangari, MD

  University of Arkansas

  PRINCIPAL INVESTIGATOR

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: March 27, 2009
• First Posted: March 30, 2009
• Study Start: March 1, 2009
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: July 1, 2025

Record last verified: 2025-06

Locations

US (1)