UARK 2003-33, Total Therapy III - Full Text View

Sponsor:	University of Arkansas
Information provided by (Responsible Party):	University of Arkansas
ClinicalTrials.gov Identifier:	NCT00081939

Purpose

There have been two previous Total Therapy studies for multiple myeloma (MM) at the Myeloma Institute for Research and Therapy (MIRT): Total Therapy I (from 1989 through 1994) and Total Therapy II (from 1996 to 2004). Results have shown that patients treated on these studies had better outcomes (meaning patients have lived longer and had better responses to treatment) when compared to patients treated with standard chemotherapy.

With this new study, Total Therapy III, researchers will take what they have learned from the first two studies and add new treatment strategies to try to improve the outcomes even more, especially for patients with chromosome abnormalities.

Condition	Intervention	Phase
Multiple Myeloma	Drug: Velcade Drug: Thalidomide	Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 2 Study Incorporating Bone Marrow Microenvironment (ME) Co-Targeting Bortezomib Into Tandem Melphalan-Based Autotransplants With DT PACE for Induction/Consolidation and Thalidomide + Dexamethasone for Maintenance

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Multiple Myeloma

Drug Information available for: Thalidomide Bortezomib

U.S. FDA Resources

Further study details as provided by University of Arkansas:

Primary Outcome Measures:

A historical comparison with TT II (Thalidomide arm), whether two cycles of VDTPACE induction (instead of four induction cycles in TT II) followed by more timely MEL 200-based transplant with DEX + THAL between transplants can: [ Time Frame: Participants/data will be followed and assessed for an expected average of 3 years ] [ Designated as safety issue: No ]
1.1.1 Increase the CR frequency from 50% to 60% at 18 months from initiation of therapy; [ Time Frame: Participants/data will be followed and assesed for an expected average of 18 months ] [ Designated as safety issue: No ]
1.1.2 Increase > n-CR rate pre-transplant #1 from 20% to 40%; [ Time Frame: Participants/data will be followed and assessed for an expected average of 1 year ] [ Designated as safety issue: No ]
1.1.3 Raise 2-year EFS rates from 55% to 75% in patients with CA and from 80% to 95%, in patients without CA. [ Time Frame: Participants/data will be followed and assessed for an expected average of 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

1.2 Bortezomib can be safely incorporated into well tested DT-PACE induction (VDT-PACE) with PBSC mobilization, DT-PACE consolidation after MEL 200 tandem transplant and into DEX + THAL maintenance. [ Time Frame: Participants/data will be followed and assessed for an expected average of 1 year ] [ Designated as safety issue: Yes ]
1.2.1 Increasing dosing frequency of bortezomib 1.0 mg/m2 compromises PBSC procurement after DTPACE with a target yield of > 20 x 106 CD34 cells/kg. [ Time Frame: Participants/data will be followed and assessed for an expected average of 1 year ] [ Designated as safety issue: Yes ]
1.2.2 DEX + THAL can be administered during ongoing hematopoietic recovery after first and second autotransplant without compromising subsequent VDTPACE tolerance. [ Time Frame: Participants/data will be followed and assessed for an expected average of 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	300
Study Start Date:	January 2004
Estimated Study Completion Date:	January 2014
Estimated Primary Completion Date:	January 2014 (Final data collection date for primary outcome measure)

Intervention Details:

Two cycles of induction on days 1,4,8,11 at 1.0mg/m^2. Two cycles of consolidation on days 1,4,8,11 at 1.0mg/m^2. Maintenance year one 1.0mg/m^2 1,4,8,11 q 28 days.

Two cycles of VDTPACE 200mg thal days 4-7(cycle 1)and days 1-4 cycle 2 interim Thal 50mg qd between VTDPACE cycles and between cycle 2 and transplant. Thal 100mg between transplants d/c 7 days prior to each transplant. Consolidation therapy cycles 3 and 4 VDTPACE 200mg days 1-4 both cycles. Interim maintenance to maintenance 100mg qd. Maintenance year 1 thal 100mg qd. Maintenance years 2 and 3 Thal 100mg qd.

Detailed Description:

1.1 To determine, in a historical comparison with TT II (Thalidomide arm), whether two cycles of VDTPACE induction (instead of four induction cycles in TT II) followed by more timely MEL 200-based transplant with DEX + THAL between transplants can:

1.1.1 Increase the CR frequency from 50% to 60% at 18 months from initiation of therapy;

1.1.2 Increase > n-CR rate pre-transplant #1 from 20% to 40%;

1.1.3 Raise 2-year EFS rates from 55% to 75% in patients with CA and from 80% to 95%, in patients without CA.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Induction Inclusion Criteria:

Patients must have newly diagnosed active MM requiring treatment. Patients with a previous history of smoldering myeloma will be eligible if there is evidence of progressive disease requiring chemotherapy.
Protein criteria must be present (quantifiable M-component of IgG, IgA, IgD, or IgE and/or urinary kappa or lambda light chain or Bence Jones protein) in order to evaluate response. Non-secretory patients are eligible provided the patient has > 20% plasmacytosis or multiple (>3) focal plasmacytomas on MRI or diffuse hyperintense signal on STIR images in the absence of hematopoietic growth factors.
Patients must have received no more than one cycle of prior chemotherapy for this disease. Patients may have received prior radiotherapy provided approval has been obtained by the Principal Investigator.
Patients must be < or = 75 years of age at the time of initial registration.
Ejection fraction by ECHO or MUGA >40% performed within 60 days prior to registration.
Patients must have adequate pulmonary function studies > or = 50% of predicted on mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) > or =50% of predicted, within 60 days of registration. If the patient is unable to complete pulmonary function tests due to MM related pain or condition, there must be a pulmonary consult documenting that the patient is a candidate for high dose therapy.
Patients must have a performance status of 0-2 based on SWOG criteria. Patients with a poor performance status (3-4), based solely on bone pain, will be eligible.
All patients must be informed of the investigational nature of this study and must have signed an IRB-approved informed consent in accordance with institutional and federal guidelines.

Induction Exclusion Criteria:

Platelet count < 30 x 10^9/L, unless myeloma-related
ANC < 1.0 X 10^9/L, unless myeloma-related
Grade > or =2 peripheral neuropathy
Hypersensitivity to bortezomib, boron, or mannitol
Uncontrolled diabetes.
Recent (< or =6 months) myocardial infarction, unstable angina, difficult to control congestive heart failure, uncontrolled hypertension, or difficult to control cardiac arrhythmias.
Evidence of chronic obstructive or chronic restrictive pulmonary disease.
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 been disease free for at least three years.
Patients must not have significant co-morbid medical conditions or uncontrolled life threatening infection.
Pregnant or nursing women. Women of child-bearing potential must have a negative pregnancy test documented within one week of registration. Women and men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00081939

Locations

United States, Arkansas
University of Arkansas for Medical Sciences/MIRT
Little Rock, Arkansas, United States, 72205

Sponsors and Collaborators

University of Arkansas

Investigators

Principal Investigator:

Bart Barlogie, MD, PhD

UAMS

More Information

Additional Information:

Click here for more information about UAMS This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	University of Arkansas
ClinicalTrials.gov Identifier:	NCT00081939 History of Changes
Other Study ID Numbers:	UARK 2003-33
Study First Received:	April 27, 2004
Last Updated:	September 2, 2011
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Thalidomide

Bortezomib
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Protease Inhibitors

ClinicalTrials.gov processed this record on February 12, 2012