Multiple MyelomaPhase 2NCT00580372
UARK 89-001 Phase II Study of Intensive "TOTAL THERAPY" For Untreated or Minimally Treated Patients With Multiple Myeloma
A Phase 2 study testing VAD, High-Dose cyclophosphamide and Hemopoietic stem cell procurement in people with Multiple Myeloma, run by University of Arkansas at 1 site in United States.
Trial summary
This experimental study evaluates the effects of a series of intensive drug regimens as initial treatment for Multiple Myeloma followed by 2 bone marrow transplantations 4-6 months apart in support of high-dose Melphalan, followed by Interferon treatment indefinitely. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- VAD, High-Dose cyclophosphamide and Hemopoietic stem cell procurement
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 231 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2002to Oct 2015
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Previously untreated patients with the diagnosis of multiple myeloma are eligible. Similarly, patients who have not had more than one cycle of standard chemotherapy or up to one month of interferon and/or glucocorticoids are eligible.
- Patients must have objective evidence of, or be symptomatic from, complications due to myeloma (e.g., bone pain from fractures, weakness from anemia). Asymptomatic patients may be treated only if the diagnosis is confirmed and if there is evidence of increasing tumor mass (e.g., rising myeloma protein and/or increasing lytic lesions).
- Asymptomatic patients with idiopathic monoclonal peaks, localized plasmacytomas, or indolent, asymptomatic myeloma are not eligible for this study. Any patient without documented increasing disease and/or clearly symptomatic disease is not eligible.
- Measurable, direct manifestations of myeloma must be present, such as monoclonal serum or urine globulins. Plasma cell tumors must also be documented. Patients without protein criteria are eligible if bone marrow has > 30% plasmacytosis documented by bilateral bone marrow aspirations and biopsies.
- Patients with all stages of multiple myeloma (I, II, III) are eligible. Necessary baseline studies must be obtained to determine the stage prior to registration.
- Patients may have received local radiation to painful compression fractures or lytic bone lesions, provided that adequate autologous bone marrow can still be harvested. Patients presenting with clinical conditions requiring radiotherapy (e.g. spinal cord compression) may proceed with concurrent local radiation and VAD. Should compression fractures of known prestudy lytic lesions occur during later, more myelosuppressive phases of induction therapy, radiotherapy should be completed first prior to proceeding with high-dose cyclophosphamide, EDAP or melphalan.
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- Patients should be older than 15 years of age and may be up to 65 years old.
- Pregnant females are excluded from study.
- Eligibility criteria change with the progress through the different phases of the induction program towards the two cycles of marrow-ablative therapy. These are summarized in the eligibility checklist.
- Briefly, prior to VAD, patients must have a normal cardiac ejection fraction of > 50% (on ECHO cardiography or MUGGA scan), and fairly normal liver function tests (bilirubin < 2 mg% and serum transaminase levels less than 2 x normal). Screening for viral hepatitis should be negative for acute or chronic active hepatitis. Positive antibody (anti-HAV, HBSAb) suggestive of remote exposure is acceptable. However, patients who test positive for Hepatitis C antibody (anti-HCV) or HIV are ineligible. Those with renal failure are eligible and should start VAD promptly and receive additional medical measures as needed. Patients presenting with infections upon presentation shall receive proper medical management prior to starting therapy. Patient's performance status is not a criterion for entry on the VAD portion of this program.
- After 2 or 3 cycles of VAD, serum creatinine levels must be 2 mg% and carbon monoxide diffusion capacity 50%. Cardiac and liver function requirements as with VAD.
- Not until reaching the high-dose melphalan stage of 70 mg/M2 will there be a requirement for Zubrod performance of 0 and 1 which must also be fulfilled with each of the 2 marrow-ablative doses of melphalan (200 mg/M2).
Who cannot join
- Less than 10 x 108 cells/kg stored.
- a granulocyte count of less than 1500/µl and a platelet count less than 150,000/µl.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Arkansas for Medical Sciences/MIRT
Little Rock, Arkansas, 72205
About this study
Official title: Phase II Study of Intensive "TOTAL THERAPY" for Untreated or Minimally Treated Patients With Multiple Myeloma
This experimental study evaluates the effects of a series of intensive drug regimens as initial treatment for Multiple Myeloma followed by 2 bone marrow transplantations 4-6 months apart in support of high-dose Melphalan, followed by Interferon treatment indefinitely.
- Conditions
- Multiple Myeloma
- Being tested
- VAD, High-Dose cyclophosphamide, Hemopoietic stem cell procurement, EDAP, Autologous Hemopoietic Stem Cell Transplant 1
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VADDrug
3 Cycles (3rd cycle optional): Vincristine 0.5 mg/d d 1 - 4 CI Adriamycin 10 mg/m2/d d 1 - 4 CI Dexamethasone 40 mg/d d 1-4, 9-12, 17-20
High-Dose cyclophosphamideDrug
Approximately 5-6 weeks after VAD 2 or 3:
Cytoxan 1.2g/m2/d d 1 - 5 Mesna 3.6 g/m2 d 1
Hemopoietic stem cell procurementProcedure or surgery
Collection target = 10 x 10^6 cells/kg
EDAPDrug
Approximately 5-6 weeks after high-dose cyclophosphamide Etoposide 100 mg/m2/d d 1 - 4 CI Cisplatin 25 mg/m2/d d 1 - 4 CI Ara C l g/m2 d 5 Dexamethasone 40 mg d 1-5
Autologous Hemopoietic Stem Cell Transplant 1Procedure or surgery
4-6 weeks after EDAP: Melphalan 100 mg/m2 days -1 and -2
Autologous Hemopoietic Stem Cell Transplant 2Procedure or surgery
4-6 months after Transplant 1: Melphalan 100 mg/m2 days -1 and -2
MaintenanceDrug
3 months after Transplant 2: Intron A 3 X 10^6 units /m2 M-W-F subcutaneously until relapse
| Study group | Role | What they receive |
|---|---|---|
| Study Treatment | Experimental | Protocol therapy consists of a remission induction phase with mutually non-cross resistant combinations of vincristine, adriamycin, dexamethasone (VAD), high-dose cyclophosphamide with stem cell procurement and etoposide, dexamethasone, cytarabine, cisplatin (EDAP) followed by two courses of melphalan-based high-dose therapy supported by autologous stem cell transplants 4-6 months apart. Maintenance with interferon alpha will be administered until disease progression. Receives: Drug: VAD; Drug: High-Dose cyclophosphamide; Procedure: Hemopoietic stem cell procurement; Drug: EDAP; Procedure: Autologous Hemopoietic Stem Cell Transplant 1; Procedure: Autologous Hemopoietic Stem Cell Transplant 2; Drug: Maintenance |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants That Are Relapse-free 5 Years After Initial Therapy
Relapse is defined by the unequivocal objective evidence of recurrent disease such as:
myeloma-related cytogenetic abnormalities; bone marrow plasmacytosis >10% or >5% light chain restricted, non-diploid, plasma cells on clg/DNA; new skeletal or MRI lesions; hypercalcemia not explained by any other cause; or reappearance of M-protein in blood or urine not related to immune recovery, recent infection, and present for >2 months.
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2007 (estimated)
- Study startAug 2002
- Primary completionOct 2015
- Study completionOct 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by University of ArkansasThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 231 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arkansas
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Bart Barlogie, MD, PhD, Principal investigator, University of Arkansas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00580372
- Sponsor's protocol ID
- 01332
- Status last verified
- Aug 2016
- First submitted
- 18 Dec 2007
- Last updated
- 20 Sep 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Al Hadidi S, Ababneh OE, Schinke CD, Thanendrarajan S, Siegel ER, Bailey C, Smith R, Panozzo SB, Zangari M, Tricot G, Shaughnessy JD Jr, Zhan F, Sawyer J, Barlogie B, van Rhee F. Long-Term Follow-Up of Patients With Multiple Myeloma Treated on Earlier Total Therapy Protocols: A Secondary Analysis of 3 Clinical Trials. JAMA Oncol. 2025 Aug 1;11(8):910-915. doi: 10.1001/jamaoncol.2025.1394.
PubMed 40471585
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study of Intensive "TOTAL THERAPY" for Untreated or Minimally Treated Patients With Multiple Myeloma
- ClinicalTrials.gov ID
- NCT00580372
- Acronym / sponsor ID
- 01332
- Conditions
- Multiple Myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 231 participants (actual)
- Lead sponsor
- University of ArkansasUniversity, hospital or other
- Study start
- Aug 2002
- Primary completion
- Oct 2015 (actual)
- Study completion
- Oct 2015 (actual)
- First posted
- 24 Dec 2007 (estimated)
- Results
- Posted 20 Sep 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This experimental study evaluates the effects of a series of intensive drug regimens as initial treatment for Multiple Myeloma followed by 2 bone marrow transplantations 4-6 months apart in support of high-dose Melphalan, followed by Interferon treatment indefinitely.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study Treatment | Experimental | Drug: VAD, Drug: High-Dose cyclophosphamide, Procedure: Hemopoietic stem cell procurement, Drug: EDAP, Procedure: Autologous Hemopoietic Stem Cell Transplant 1, Procedure: Autologous Hemopoietic Stem Cell Transplant 2, Drug: MaintenanceProtocol therapy consists of a remission induction phase with mutually non-cross resistant combinations of vincristine, adriamycin, dexamethasone (VAD), high-dose cyclophosphamide with stem cell procurement and etoposide, dexamethasone, cytarabine, cisplatin (EDAP) followed by two courses of melphalan-based high-dose therapy supported by autologous stem cell transplants 4-6 months apart. Maintenance with interferon alpha will be administered until disease progression. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Previously untreated patients with the diagnosis of multiple myeloma are eligible. Similarly, patients who have not had more than one cycle of standard chemotherapy or up to one month of interferon and/or glucocorticoids are eligible.
- Patients must have objective evidence of, or be symptomatic from, complications due to myeloma (e.g., bone pain from fractures, weakness from anemia). Asymptomatic patients may be treated only if the diagnosis is confirmed and if there is evidence of increasing tumor mass (e.g., rising myeloma protein and/or increasing lytic lesions).
- Asymptomatic patients with idiopathic monoclonal peaks, localized plasmacytomas, or indolent, asymptomatic myeloma are not eligible for this study. Any patient without documented increasing disease and/or clearly symptomatic disease is not eligible.
- Measurable, direct manifestations of myeloma must be present, such as monoclonal serum or urine globulins. Plasma cell tumors must also be documented. Patients without protein criteria are eligible if bone marrow has > 30% plasmacytosis documented by bilateral bone marrow aspirations and biopsies.
- Patients with all stages of multiple myeloma (I, II, III) are eligible. Necessary baseline studies must be obtained to determine the stage prior to registration.
Key exclusion criteria (2 listed)
- Less than 10 x 108 cells/kg stored.
- a granulocyte count of less than 1500/µl and a platelet count less than 150,000/µl.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VAD3 Cycles (3rd cycle optional): Vincristine 0.5 mg/d d 1 - 4 CI Adriamycin 10 mg/m2/d d 1 - 4 CI Dexamethasone 40 mg/d d 1-4, 9-12, 17-20 | Drug | Study Treatment |
| High-Dose cyclophosphamideApproximately 5-6 weeks after VAD 2 or 3: Cytoxan 1.2g/m2/d d 1 - 5 Mesna 3.6 g/m2 d 1 | Drug | Study Treatment |
| Hemopoietic stem cell procurementCollection target = 10 x 10^6 cells/kg | Procedure or surgery | Study Treatment |
| EDAPApproximately 5-6 weeks after high-dose cyclophosphamide Etoposide 100 mg/m2/d d 1 - 4 CI Cisplatin 25 mg/m2/d d 1 - 4 CI Ara C l g/m2 d 5 Dexamethasone 40 mg d 1-5 | Drug | Study Treatment |
| Autologous Hemopoietic Stem Cell Transplant 14-6 weeks after EDAP: Melphalan 100 mg/m2 days -1 and -2 | Procedure or surgery | Study Treatment |
| Autologous Hemopoietic Stem Cell Transplant 24-6 months after Transplant 1: Melphalan 100 mg/m2 days -1 and -2 | Procedure or surgery | Study Treatment |
| Maintenance3 months after Transplant 2: Intron A 3 X 10^6 units /m2 M-W-F subcutaneously until relapse | Drug | Study Treatment |
Primary outcome
Percentage of Participants That Are Relapse-free 5 Years After Initial Therapy
Time frame: 5 years
Relapse is defined by the unequivocal objective evidence of recurrent disease such as: myeloma-related cytogenetic abnormalities; bone marrow plasmacytosis >10% or >5% light chain restricted, non-diploid, plasma cells on clg/DNA; new skeletal or MRI lesions; hypercalcemia not explained by any other cause; or reappearance of M-protein in blood or urine not related to immune recovery, recent infection, and present for >2 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40471585Al Hadidi S, Ababneh OE, Schinke CD, Thanendrarajan S, Siegel ER, Bailey C, Smith R, Panozzo SB, Zangari M, Tricot G, Shaughnessy JD Jr, Zhan F, Sawyer J, Barlogie B, van Rhee F. Long-Term Follow-Up of Patients With Multiple Myeloma Treated on Earlier Total Therapy Protocols: A Secondary Analysis of 3 Clinical Trials. JAMA Oncol. 2025 Aug 1;11(8):910-915. doi: 10.1001/jamaoncol.2025.1394.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bart Barlogie, MD, PhD principal investigator
University of Arkansas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing VAD, High-Dose cyclophosphamide and Hemopoietic stem cell procurement in people with Multiple Myeloma, run by University of Arkansas at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Sep 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants That Are Relapse-free 5 Years After Initial Therapy (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00580372, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2016.