UARK 2006-66, Total Therapy 3B: An Extension of UARK 2003-33 Total Therapy

Sponsor

University of Arkansas (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00572169

Collaborator

(none)

177

Enrollment

Location

Arm

213

Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

With this study - Total Therapy IIIB - researchers are extending the findings of Total Therapy III based what they have learned from the first two studies (Total Therapy I and II), with new research strategies designed to explore why chromosome abnormalities found in persons with multiple myeloma affect the outcome of drug therapy used in this disease."

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Velcade Drug: Thalidomide Drug: Dexamethasone Drug: Adriamycin Drug: Cisplatin Drug: Cyclophosphamide Drug: Etoposide	Phase 3

Detailed Description

It is well known that myeloma patients with chromosome abnormalities are at higher risk because their disease tends to be more aggressive and does not respond to treatment as well as patients without chromosome abnormalities. When researchers at the Myeloma Institute looked at the results of Total Therapy II, they found that although research subjects with chromosome abnormalities had better outcomes (how many responded, and how long they survived) than those treated with standard chemotherapy; still their outcomes did not improve significantly with Total Therapy II, when compared to Total Therapy I.

The research in this new study is designed to target this high-risk group of individuals with chromosomal abnormalities. However, it is hoped that both groups of research participants - those with and without chromosome abnormalities - will derive benefit from changes made in this new research study.

Study Design

Study Type:

Interventional

Actual Enrollment :

177 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study Incorporating Bone Marrow Microenvironment (ME) - Co-Targeting Bortezomib Into Tandem Melphalan-Based Autotransplants With DTPACE for Induction/Consolidation and Thalidomide + Dexamethasone for Maintenance

Study Start Date :

Nov 1, 2006

Anticipated Primary Completion Date :

Aug 1, 2024

Anticipated Study Completion Date :

Aug 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VDTPACE Velcade, Dexamethasone, Thalidomide, Cisplatinin, Adriamycin, Cyclophosphamide and Etoposide	Drug: Velcade Will be given in central venous catheter Other Names: Bortezomib, PS-341 Drug: Thalidomide Capsule taken by mouth Other Names: Thalomid Drug: Dexamethasone A pill taken by mouth Other Names: Decadron, NSC-34521 Drug: Adriamycin Given into the vein (IV) by a continuous infusion through a central catheter Other Names: Doxorubicin, NSC-123127 Drug: Cisplatin Given into the vein (IV) by a continuous infusion through a central catheter Other Names: Cis-diamminedichloroplatinum [CDDP], Platinol, NSC-119875 Drug: Cyclophosphamide Given into the vein (IV) by a continuous infusion through a central catheter Other Names: Cytoxan, NSC-26271 Drug: Etoposide Given into the vein (IV) by a continuous infusion through a central catheter Other Names: VP-16), Vepesid®, Ethylidene-Lignan P., NSC-141540

Arm

Intervention/Treatment

Experimental: VDTPACE

Velcade, Dexamethasone, Thalidomide, Cisplatinin, Adriamycin, Cyclophosphamide and Etoposide

Drug: Velcade

Will be given in central venous catheter

Other Names:

Bortezomib, PS-341

Drug: Thalidomide

Capsule taken by mouth

Other Names:

Thalomid

Drug: Dexamethasone

A pill taken by mouth

Other Names:

Decadron, NSC-34521

Drug: Adriamycin

Given into the vein (IV) by a continuous infusion through a central catheter

Other Names:

Doxorubicin, NSC-123127

Drug: Cisplatin

Given into the vein (IV) by a continuous infusion through a central catheter

Other Names:

Cis-diamminedichloroplatinum [CDDP], Platinol, NSC-119875

Drug: Cyclophosphamide

Given into the vein (IV) by a continuous infusion through a central catheter

Other Names:

Cytoxan, NSC-26271

Drug: Etoposide

Given into the vein (IV) by a continuous infusion through a central catheter

Other Names:

VP-16), Vepesid®, Ethylidene-Lignan P., NSC-141540

Outcome Measures

Primary Outcome Measures

To find out if outcomes of participants in this study will be better when compared to individuals who participated in Total Therapy II, especially those with chromosome abnormalities. [48 months]

Secondary Outcome Measures

To find out if outcomes and incidence of toxicities of participants in this study will be better when compared to individuals who participated in Total Therapy III. [48 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 serum M-component of IgG, IgA, IgD, or IgE; urinary kappa or lambda light chain; or serum free light chain (SFLC) levels in order to evaluate response. Non-secretory patients are eligible provided the patient has > 20% plasmacytosis OR multiple (>3) focal plasmacytomas or focal lesions 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 or one month of prior chemotherapy for this disease. Patients may have received prior radiotherapy provided approval has been obtained by the Principal Investigator.
Patients must be <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 > 50% of predicted on mechanical aspects (FEV1, FVC, etc) and diffusion capacity (DLCO) > 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, exception may be granted if the principal investigator documents 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.

Exclusion Criteria:

Platelet count < 30 x 109/L, unless myeloma-related.
5.1.2.2 Grade > 2 peripheral neuropathy.
Hypersensitivity to bortezomib, boron, or mannitol.
Uncontrolled diabetes.
Recent (< 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.
Patients must not have light chain deposition disease or creatinine > 3 mg/dl
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 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.