Phase II Trial for Patients Not Qualifying for TT4 and TT5 Protocols Because of Prior Therapy (No Prior Transplant)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by University of Arkansas
Sponsor:
Information provided by (Responsible Party):
University of Arkansas
ClinicalTrials.gov Identifier:
NCT00871013
First received: March 27, 2009
Last updated: June 2, 2014
Last verified: June 2014

March 27, 2009
June 2, 2014
March 2009
March 2015   (final data collection date for primary outcome measure)
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. . [ Time Frame: Two years ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00871013 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
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Phase II Trial for Patients Not Qualifying for TT4 and TT5 Protocols Because of Prior Therapy (No Prior Transplant)
Phase II Trial for Patients Not Qualifying for TT4 and TT5 Protocols Because of Prior Therapy (No Prior Transplant)

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.

  • To find out if giving multi-agent chemotherapy in lower and more frequent doses to make the timely delivery of chemotherapy cycles possible, will result in better myeloma responses
  • To find out if changing the way the drugs are given during the transplant phase will also result in fewer side effects, while still being effective
  • To find out if giving treatment between transplants (called "inter-therapy") will prevent the myeloma from re-growing between transplants
  • To find out if long-term maintenance therapy will result in longer remissions
  • To find out what the effects (good and bad) of this overall treatment will be
  • To learn more about the biology and genetics of multiple myeloma by performing imaging tests and collecting blood, bone marrow aspirate and biopsies, and biopsies of lesions seen on MRI or PET scans. Bone marrow aspirates and biopsies are tissue sample collected from the bone cavity.
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Myeloma
Drug: Velcade, Revlimid, Dexamethasone, Melphalan, Cisplatin, Thalidomide

First Transplant Bortezomib (Velcade) By vein Day -5 and Day -2

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

Other Names:
  • Bortezomib (Velcade)
  • CC-5013 (Revlimid)
  • CDDP, Platinol (Cisplatin)
  • Decadron (Dexamethasone)
  • Alkeran (Melphalan)
  • Thalomid (Thalidomide)
Not Provided
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
100
March 2015
March 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients with symptomatic multiple myeloma (MM), with at least one prior line of chemotherapy.
  • 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.

Exclusion Criteria:

  • 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.
Both
18 Years to 75 Years
No
Contact: Nathan Petty 501-526-6990 ext 2435 pettynathanm@uams.edu
United States
 
NCT00871013
UARK 2008-03
Yes
University of Arkansas
University of Arkansas
Not Provided
Principal Investigator: Bart Barlogie, MD, PhD University of Arkansas
University of Arkansas
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP