Completed

UARK 98-026, Total Therapy II - A Phase III Study for Newly Diagnosed Multiple Myeloma Evaluating Anti-Angiogenesis With Thalidomide and Post-Transplant Consolidation Chemotherapy

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What is being tested

Thalidomide

+ Ara-C
+ BCNU
Drug
Who is being recruted

Blood Protein Disorders
+11

+ Cardiovascular Diseases
+ Hematologic Diseases
From 18 to 75 Years
See all eligibility criteria
How is the trial designed

Treatment Study

Phase 3
Interventional
Study Start: August 1998
See protocol details

Summary

Principal SponsorUniversity of Arkansas
Last updated: January 18, 2026
Sourced from a government-validated database.Claim as a partner
Study start date: August 1, 1998Actual date on which the first participant was enrolled.

Treatment will be given in 4 phases or steps: Induction, Transplant 1 and 2, Consolidation, and maintenance. Induction is designed to induce (or bring about) myeloma into remission. Each patient enrolled on this study will be randomly assigned to receive the above treatment alone or in combination with a drug called thalidomide. Some patients may be eligible to receive the transplant as an outpatient, based on general health and other factors.After recovery from the transplant phase of the study (approximately 6 weeks), patients originally assigned to thalidomide will resume taking it and will continue taking it throughout the rest of the study treatment. All patients will receive post-transplant consolidation treatment, which in earlier studies has been found to be helpful in maintaining patients response after transplant. Therefore, all patients will receive a combination of drugs called "D PACE" which consists of Dexamethasone, Cis-Platinum, Adriamycin, Cyclophosphamide, and Etoposide. If you are also taking thalidomide, you will continue taking it throughout, and the treatment is called "DT PACE" to include the thalidomide. No sooner than 4 weeks, and no later than 12 weeks after consolidation and if your myeloma remains in remission after consolidation therapy is complete, you will begin the last phase of the study, which is maintenance. Maintenance is designed to keep your myeloma in remission long-term.

Official TitleUARK 98-026, Total Therapy II - A Phase III Study for Newly Diagnosed Multiple Myeloma Evaluating Anti-Angiogenesis With Thalidomide and Post-Transplant Consolidation Chemotherapy 
Principal SponsorUniversity of Arkansas
Last updated: January 18, 2026
Sourced from a government-validated database.Claim as a partner

Protocol

This section provides details of the study plan, including how the study is designed and what the study is measuring.
Design Details
668 patients to be enrolledTotal number of participants that the clinical trial aims to recruit.
Treatment Study
These studies test new ways to treat a disease, condition, or health issue. The goal is to see if a new drug, therapy, or approach works better or has fewer side effects than existing options.

How participants are assigned to different groups/arms
In this clinical study, participants are placed into groups randomly, like flipping a coin. This ensures that the study is fair and unbiased, making the results more reliable. By assigning participants by chance, researchers can better compare treatments without external influences.

Other Ways to Assign Participants
Non-randomized allocation
: Participants are assigned based on specific factors, such as their medical condition or a doctor's decision.

None (Single-arm trial)
: If the study has only one group, all participants receive the same treatment, and no allocation is needed.

How treatments are given to participants
Participants are divided into different groups, each receiving a specific treatment at the same time. This helps researchers compare how well different treatments work against each other.

Other Ways to Assign Treatments
Single-group assignment
: Everyone gets the same treatment.

Cross-over assignment
: Participants switch between treatments during the study.

Factorial assignment
: Participants receive different combinations of treatments.

Sequential assignment
: Participants receive treatments one after another in a specific order, possibly based on individual responses.

Other assignment
: Treatment assignment does not follow a standard or predefined design.

How the interventions assigned to participants is kept confidential
Everyone involved in the study knows which treatment is being given. This is typically used when it's not possible or necessary to hide the treatment details from participants or researchers.

Other Ways to Mask Information
Single-blind
: Participants do not know which treatment they are receiving, but researchers do.

Double-blind
: Neither participants nor researchers know which treatment is given.

Triple-blind
: Participants, researchers, and outcome assessors do not know which treatment is given.

Quadruple-blind
: Participants, researchers, outcome assessors, and care providers all do not know which treatment is given.

Eligibility

Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.
Conditions
Criteria
Any sexBiological sex of participants that are eligible to enroll.
From 18 to 75 YearsRange of ages for which participants are eligible to join.
Healthy volunteers not allowedIf individuals who are healthy and do not have the condition being studied can participate.
Conditions
Pathology
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Multiple Myeloma
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
Hemostatic Disorders
Neoplasms, Plasma Cell
Criteria

Inclusion Criteria: * Patients must have newly diagnosed active multiple myeloma 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 in order to evaluate response.Non-secretory patients are eligible provided the patient has \> or = 20% plasmacytosis or multiple (\>3) focal plasmacytomas on MRI or diffuse hyperintense signal on STIR images in the absence of hematopoietic growth factors is seen. * All necessary baseline studies for determining stage, bloodwork, and bone marrow must be obtained within 35 days prior to registration. * Patients must have received no more than one cycle of prior chemotherapy including one month of Dexamethasone and Thalidomide for this disease. Patients may have received prior radiotherapy provided approval has been obtained by one of the study coordinators. * 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. * Patients with renal failure, even if on dialysis, are eligible if it is felt to be due to myeloma and if the duration of renal failure does not exceed two months * Patients must be 75 years of age or less at the time of registration * All patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines. * If medically appropriate, patients with pathologic fractures, pneumonia at diagnosis or hyperviscosity with shortness of breath should have these conditions attended to prior to registration. Exclusion Criteria: * Patients must not have significant co-morbid medical conditions or uncontrolled life threatening infection * Patients must not have uncontrolled diabetes * Patients with recent (\< or =6 months) myocardial infarction, unstable angina, difficult to control congestive heart failure, uncontrolled hypertension, or difficult to control cardiac arrythmias are ineligible. Ejection fraction by ECHO or MUGA should be within the institutional normal range and must be performed within 42 days prior to registration. * Patients must not have a history of chronic obstructive or chronic restrictive pulmonary disease. * No prior malignancy is allowed 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.Prior malignancy is acceptable provided there has been no evidence of disease within the three-year interval and there must be no prior treatment with cytotoxic drugs that could potentially be assigned on this treatment protocol. * Pregnant or nursing women may not participate. Women of child-bearing 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 two forms of effective contraceptive method.

Study Plan

Find out more about all the medication administered in this study, their detailed description and what they involve.
Treatment Groups
Study Objectives
2 intervention groups 

are designated in this study

This study does not include a placebo group 

Treatment Groups
Group I
Active Comparator
Thalidomide 400 qod during induction.100 mg qd between transplants, post transplant pat. 200 mg qd. During year one of maintenance therapy pt will take 100mg of Thal qod and 50 mg of thal qod during second year of maintenance

All patients will be randomly assigned to receive thalidomide 400 mg as an oral, once daily dose throughout induction and 100mg between transplants after platelets are greater than 50,000μl and 200 mg post transplant consolidation, and a reduced dose of 100 mg on alternating days during the first year of maintenance and 50 mg qod thereafter versus no thalidomide. Thalidomide will be held during conditioning, transplant procedure, and recovery following transplant. It may be resumed once plateletrecovery is complete after each transplant

Cytarabine (Ara-C) 400 mg/m2 in 250 ml D5W over one hour daily for four days (on days -5, -4, -3, -2). Start infusion 30 minutes after completion of BCNU on day -5.

Carmustine (BCNU) 300 mg/m2 in 1 liter of D5W in glass bottle (protect from light) to infuse over 2 hours on day -5. Check blood pressure every 15 minutes during infusion and 30 minutes after completion

Cisplatin\* 15 mg/m2/day Continuous infusion 1-4 (DCEP CYCLE 2) Cisplatin\* 7.5 mg/m2 Continuous infusion 1-4 (DPACE cycle) \*Cisplatin doses will be modified for renal insufficiency as follows: Cisplatin dose Creatinine 15 mg/m2 (full dose) \< 1.5 mg/dl 10 mg/m2 1.6 - 2.0 mg/dl 7.5 mg/m2 2.1 - 3.0 mg/dl 0 mg (hold Cisplatin) \> 3.0 mg/dl

Cycle 2 - DCEP Cyclophosphamide 400 mg/m2/day Continuous infusion 1-4 Cycle 3 - CAD and PBSC Collection #1 Cyclophosphamide 750 mg/m2/day Continuous infusion 1-4 Cycle 4 - DCEP Cyclophosphamide 400 mg/m2/day Continuous infusion 1-4 Cytoxan/VP-16 and PBSC Collection-Cyclophosphamide 2 grams/m2 (Total dose 4 gm/m2) IV by CI 1 and 2 Post-Transplant Consolidation-Cyclophosphamide 300 mg/m2 Continuous infusion 1-4

Induction cycle 1 VAD Dexamethasone 40 mg/day PO 1-4, 9-12, 17-20 Cycle 2 - DCEP Dexamethasone 40 mg/day PO 1-4 Cycle 3 - CAD and PBSC Collection #1 Dexamethasone 40 mg/day PO 1-4 Cycle 4 - DCEP and PBSC Collection #2 Dexamethasone 40 mg/day PO 1-4 Post-Transplant Consolidation Dexamethasone 40 mg PO 1-4 Dexamethasone Consolidation Patients that do not achieve adequate platelet recovery (defined as \< 80,000/μl) will receive consolidation with Dexamethasone 40 mg x 4 days every 28 days for 1 year Maintenance year one Dexamethasone 40 mg PO q 3 months, day 1-4, 9-12, 17-20

Etoposide (VP16) 200 mg/m2 in 500 ml D5W over one hour daily for four days (on days -5, -4, -3, -2). Start infusion 30 minutes after completion of BCNU on day -5. Start infusion at completion of cytarabine on following three days

G-CSF will be administered at a dose of 10mcg/kg or GM-CSF at a dose of 10 mcg/kg. G-CSF or GM-CSF will begin one day after completion of chemotherapy and continued during repeated apheresis and discontinued upon completion of apheresis.

GM-CSF at a dose of 10 μg/kg SC, divided in 2 doses each day, will begin one day after completion of chemotherapy and continued during repeated apheresis and discontinued upon completion of apheresis.

AGENT DOSE ROUTE DAYS Intron-A 3 million units/m2 SQ TIW Thalidomide (for those randomized at initial registration) 50 mg QOD PO Every other day (qod

Etoposide (VP16) 200 mg/m2 in 500 ml D5W over one hour daily for four days (on days -5, -4, -3, -2). Start infusion 30 minutes after completion of BCNU on day -5. Start infusion at completion of cytarabine on following three days
Group II
Active Comparator
During induction, consolidation, and maintenance steps patient receives no thalidamide

Cytarabine (Ara-C) 400 mg/m2 in 250 ml D5W over one hour daily for four days (on days -5, -4, -3, -2). Start infusion 30 minutes after completion of BCNU on day -5.

Carmustine (BCNU) 300 mg/m2 in 1 liter of D5W in glass bottle (protect from light) to infuse over 2 hours on day -5. Check blood pressure every 15 minutes during infusion and 30 minutes after completion

Cisplatin\* 15 mg/m2/day Continuous infusion 1-4 (DCEP CYCLE 2) Cisplatin\* 7.5 mg/m2 Continuous infusion 1-4 (DPACE cycle) \*Cisplatin doses will be modified for renal insufficiency as follows: Cisplatin dose Creatinine 15 mg/m2 (full dose) \< 1.5 mg/dl 10 mg/m2 1.6 - 2.0 mg/dl 7.5 mg/m2 2.1 - 3.0 mg/dl 0 mg (hold Cisplatin) \> 3.0 mg/dl

Cycle 2 - DCEP Cyclophosphamide 400 mg/m2/day Continuous infusion 1-4 Cycle 3 - CAD and PBSC Collection #1 Cyclophosphamide 750 mg/m2/day Continuous infusion 1-4 Cycle 4 - DCEP Cyclophosphamide 400 mg/m2/day Continuous infusion 1-4 Cytoxan/VP-16 and PBSC Collection-Cyclophosphamide 2 grams/m2 (Total dose 4 gm/m2) IV by CI 1 and 2 Post-Transplant Consolidation-Cyclophosphamide 300 mg/m2 Continuous infusion 1-4

Induction cycle 1 VAD Dexamethasone 40 mg/day PO 1-4, 9-12, 17-20 Cycle 2 - DCEP Dexamethasone 40 mg/day PO 1-4 Cycle 3 - CAD and PBSC Collection #1 Dexamethasone 40 mg/day PO 1-4 Cycle 4 - DCEP and PBSC Collection #2 Dexamethasone 40 mg/day PO 1-4 Post-Transplant Consolidation Dexamethasone 40 mg PO 1-4 Dexamethasone Consolidation Patients that do not achieve adequate platelet recovery (defined as \< 80,000/μl) will receive consolidation with Dexamethasone 40 mg x 4 days every 28 days for 1 year Maintenance year one Dexamethasone 40 mg PO q 3 months, day 1-4, 9-12, 17-20

Doxorubicin may be further diluted in 5% dextrose or sodium chloride injection and should be administered slowly into tubing of a freely flowing intravenous infusion with great care taken to avoid extravasation.

Etoposide (VP16) 200 mg/m2 in 500 ml D5W over one hour daily for four days (on days -5, -4, -3, -2). Start infusion 30 minutes after completion of BCNU on day -5. Start infusion at completion of cytarabine on following three days

G-CSF will be administered at a dose of 10mcg/kg or GM-CSF at a dose of 10 mcg/kg. G-CSF or GM-CSF will begin one day after completion of chemotherapy and continued during repeated apheresis and discontinued upon completion of apheresis.

GM-CSF at a dose of 10 μg/kg SC, divided in 2 doses each day, will begin one day after completion of chemotherapy and continued during repeated apheresis and discontinued upon completion of apheresis.

AGENT DOSE ROUTE DAYS Intron-A 3 million units/m2 SQ TIW Thalidomide (for those randomized at initial registration) 50 mg QOD PO Every other day (qod

Etoposide (VP16) 200 mg/m2 in 500 ml D5W over one hour daily for four days (on days -5, -4, -3, -2). Start infusion 30 minutes after completion of BCNU on day -5. Start infusion at completion of cytarabine on following three days

Formulation: 1 mg/1 ml, 2 mg/2 ml, and 5 mg/ 5 ml vials. Vincristine should be administered intravenously through a freely-running IV. If it extravasates, it produces a severe local reaction with skin slough. FATAL IF GIVEN INTRATHECALLY, FOR INTRAVENOUS USE ONLY.
Study Objectives
Primary Objectives

Overall Survival at six years after initiating protocol therapy

Study Centers

These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.
This study has 1 location
Suspended
University of Arkansas for Medical Sciences/MIRTLittle Rock, United StatesSee the location
CompletedOne Study Center