Study of Multiple Myeloma Patients Relapsing or Progressing After Autologous Transplantation on Total Therapy 2

• Sponsor: University of Arkansas (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00573391
• Collaborator: (none)
• Enrollment: 5
• Location: 1
• Arms: 2
• Duration (Months): 23
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study is being done to find out if the combination of VelcadeTM with melphalan and dexamethasone (VMD) will be as effective, or even more effective as it is in combination with thalidomide and dexamethasone (VTD).

Condition or Disease	Intervention/Treatment	Phase
Multiple Myeloma	Drug: Velcade, Thalidomide, and Dexamethasone; Drug: Velcade, Melphalan, and Dexamethasone	Phase 3

Detailed Description

A new drug (bortezomib [VelcadeTM PS-341]) has been shown in recent studies to be effective in subjects with advanced multiple myeloma. There is also research that shows this drug may be even more effective when used in combination with other drugs that have been used to treat myeloma for many years (melphalan, thalidomide, and dexamethasone). This study is being done to find out if the combination of VelcadeTM with melphalan and dexamethasone (VMD) will be as effective, or even more effective as it is in combination with thalidomide and dexamethasone (VTD).

Study Design

• Study Type: Interventional
• Actual Enrollment: 5 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III Study for Patients Relapsing or Progressing After Autologous Transplantation on Total Therapy 2 (TT2, UARK 98-026): Bortezomib, Thalidomide and Dexamethasone Versus Bortezomib, Melphalan, and Dexamethasone
• Study Start Date: Aug 1, 2006
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VTD = Velcade, Thal, and Dex VTD = Velcade, Thalidomide, and Dexamethasone	Drug: Velcade, Thalidomide, and Dexamethasone; Velcade - Into vein (IV) Days 1, 4, 8, 11 Yr 1: Every 28-35 days-12 cycles Yr 2: Every 8-10 weeks- 6 cycles Thalidomide - By Mouth Days 1-28 Yr 1: Every 28-35 days-12 cycles Yr 2: Every 8-10 weeks- 6 cycles
Experimental: VMD = velcade, melphalan, and dex VMD = velcade, melphalan, and dexamethasone	Drug: Velcade, Melphalan, and Dexamethasone; Velcade - Into vein (IV) Days 1, 4, 8, 11 Yr 1: Every 28-35 days-12 cycles Yr 2: Every 8-10 weeks- 6 cycles

Outcome Measures

Primary Outcome Measures

1. Participant Survival With Velcade/Melphalan/Dexamethasone Treatment vs. Participant Survival With Velcade/Thalidomide/Dexamethasone Treatment [24 months]

   due to low accrual rates, no analyses was done to compare the new combination of Velcade/Melphalan/Dexamethasone vs. Velcade/Thalidomide/Dexamethasone

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• History of histologically documented MM previously enrolled on UARK 98-026 with relapsed or progressive disease after at least one autologous transplant.

• Patient has measurable disease in which to capture response, defined as:

• Serum M-protein level > 1.0 gm/dl (10.0 g/L) measured by serum protein electrophoresis or immunoglobulin electrophoresis

• Urinary M-protein excretion > 200 mg/24 hrs

• Bone marrow plasmacytosis of > 30percent by bone marrow aspirate and/or biopsy

• Serum Free Light Chains (By the Freelite test) > 10 mg/dL with an abnormal kappa/lambda ration.

• 50percent increase in size of lytic and/or focal lesions or development of new lesions recognized by radiographic studies.

• Performance status of 2 as per SWOG scale, unless PS of 3-4 based solely on bone pain.

• Patients must have a platelet count 50,000/mm3, unless the low platelet count is due to documented (>30 percent) extensive myeloma infiltration of the bone marrow.

• Patients must have adequate renal function defined as serum creatinine < 2.5 mg/dl.

• Patients must have adequate hepatic function defined as serum transaminases and direct bilirubin < 2 x the upper limit of normal.

• Pregnant or nursing women may not participate. Women of childbearing potential must have a negative pregnancy documented within one week of registration. Women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method.

• Male or female adults of at least 18 years of age.

• Patients must have signed and IRB-approved written informed consent form and demonstrate willingness to meet follow-up schedule and study procedure obligations

• 5 x 106 CD34 cells/kg in storage strongly desired, but not mandated

Exclusion Criteria:

• Not previously enrolled on UARK 98-026.

• Has received salvage therapy after coming off UARK 98-026.

• Evidence of POEMS Syndrome..

• Significant neurotoxicity interfering with ADL.

• Platelet count < 50,000/mm3

• Clinically significant hepatic dysfunction as noted by bilirubin or AST >3 times the upper normal limit or clinically significant concurrent hepatitis.

• New York Hospital Association (NYHA) Class III or Class IV heart failure.

• Myocardial infarction within the last 6 months.

• Truly non-secretory MM (no increase in serum free-light chains) in the absence of bone marrow plasmacytosis and MRI-defined focal lesions with CT-FNA-proven MM

• Uncontrolled, active infection requiring IV antibiotics.

• Patients with a history of treatment for clinically significant ventricular cardiac arrhythmias.

• Poorly controlled hypertension, diabetes mellitus, or other serious or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol.

• Pregnant or potential for pregnancy. Women of childbearing potential will have a pregnancy test at screening, and will be required to use a medically approved contraceptive method. Pregnancy testing will be performed prior to administration of each dose of study drug.

• Breast-feeding women may not participate.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205

Sponsors and Collaborators

• University of Arkansas

Investigators

• Principal Investigator: Bart Barlogie, MD, PhD, University of Arkansas

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00573391
• Other Study ID Numbers: 2006-05
• First Posted: Dec 14, 2007
• Last Update Posted: Aug 12, 2011
• Last Verified: Jul 1, 2011

• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Thalidomide; Dexamethasone; Dexamethasone acetate; Melphalan; Bortezomib; BB 1101

Study Results

Participant Flow

Arm/Group Title	Velcade, Thalidomide, and Dexamethasone	VMD With Melphalan Dose Escalation
Arm/Group Description	Velcade 1.0 mg/m^2 Velcade 1.3 mg/m^2 D1,4, 8, 11 (x 6 cycles, then 1.0 mg/m^2 (for cycles 7-12) Thalidomide 100 mg D1-28 Dexamethasone 20 mg D1-4 and 8-11	VMD: Velcade 1.3 mg/m^2 D1, 4, 7, 10 (x6 mo, then 1.0 mg/m^2) Melphalan 4 (6, 8, 10) mg/m^2 D1, 4, 7, 10 dose escalation Dexamethasone 20 mg 1-4 and 7-10
Period Title: Overall Study
STARTED	3	2
COMPLETED	0	0
NOT COMPLETED	3	2

Baseline Characteristics

Arm/Group Title	Velcade, Thalidomide, and Dexamethasone	VMD With Melphalan Dose Escalation	Total
Arm/Group Description	Velcade 1.0 mg/m^2 Velcade 1.3 mg/m^2 D1,4, 8, 11 (x 6 cycles, then 1.0 mg/m^2 (for cycles 7-12) Thalidomide 100 mg D1-28 Dexamethasone 20 mg D1-4 and 8-11	VMD: Velcade 1.3 mg/m^2 D1, 4, 7, 10 (x6 mo, then 1.0 mg/m^2) Melphalan 4 (6, 8, 10) mg/m^2 D1, 4, 7, 10 dose escalation Dexamethasone 20 mg 1-4 and 7-10	Total of all reporting groups
Overall Participants	3	2	5
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	2 66.7%	2 100%	4 80%
>=65 years	1 33.3%	0 0%	1 20%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	3 100%	2 100%	5 100%

Outcome Measures

1. Primary Outcome

Title	Participant Survival With Velcade/Melphalan/Dexamethasone Treatment vs. Participant Survival With Velcade/Thalidomide/Dexamethasone Treatment
Description	due to low accrual rates, no analyses was done to compare the new combination of Velcade/Melphalan/Dexamethasone vs. Velcade/Thalidomide/Dexamethasone
Time Frame	24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Velcade, Thalidomide, and Dexamethasone	VMD With Melphalan Dose Escalation
Arm/Group Description	Velcade 1.0 mg/m^2 Velcade 1.3 mg/m^2 D1,4, 8, 11 (x 6 cycles, then 1.0 mg/m^2 (for cycles 7-12) Thalidomide 100 mg D1-28 Dexamethasone 20 mg D1-4 and 8-11	VMD: Velcade 1.3 mg/m^2 D1, 4, 7, 10 (x6 mo, then 1.0 mg/m^2) Melphalan 4 (6, 8, 10) mg/m^2 D1, 4, 7, 10 dose escalation Dexamethasone 20 mg 1-4 and 7-10
Measure Participants	0	0

Adverse Events

Arm/Group Title	Velcade, Thalidomide, and Dexamethasone		VMD With Melphalan Dose Escalation
Arm/Group Description	Velcade 1.0 mg/m^2 Velcade 1.3 mg/m^2 D1,4, 8, 11 (x 6 cycles, then 1.0 mg/m^2 (for cycles 7-12) Thalidomide 100 mg D1-28 Dexamethasone 20 mg D1-4 and 8-11		VMD: Velcade 1.3 mg/m^2 D1, 4, 7, 10 (x6 mo, then 1.0 mg/m^2) Melphalan 4 (6, 8, 10) mg/m^2 D1, 4, 7, 10 dose escalation Dexamethasone 20 mg 1-4 and 7-10
All Cause Mortality
	Velcade, Thalidomide, and Dexamethasone		VMD With Melphalan Dose Escalation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Velcade, Thalidomide, and Dexamethasone		VMD With Melphalan Dose Escalation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/5 (20%)		1/5 (20%)
General disorders
fever	1/5 (20%)	1	1/5 (20%)	1
Other (Not Including Serious) Adverse Events
	Velcade, Thalidomide, and Dexamethasone		VMD With Melphalan Dose Escalation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/5 (40%)		0/5 (0%)
Cardiac disorders
secondary pulmonary hypertension	1/5 (20%)	1	0/5 (0%)	0
General disorders
pneumonia	1/5 (20%)	1	0/5 (0%)	0

Limitations/Caveats

early termination due to low accrual, no analyses

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.