UARK 89-001 Phase II Study of Intensive "TOTAL THERAPY" For Untreated or Minimally Treated Patients With Multiple Myeloma

NCT ID: NCT00580372

Last Updated: 2016-09-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 231 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2002-08-31
• Study Completion Date: 2015-10-31

Brief 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.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Study Treatment

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.

Group Type: EXPERIMENTAL

VAD

Intervention Type: DRUG

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 cyclophosphamide

Intervention Type: DRUG

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 procurement

Intervention Type: PROCEDURE

Collection target = 10 x 10\^6 cells/kg

EDAP

Intervention Type: DRUG

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 1

Intervention Type: PROCEDURE

4-6 weeks after EDAP: Melphalan 100 mg/m2 days -1 and -2

Autologous Hemopoietic Stem Cell Transplant 2

Intervention Type: PROCEDURE

4-6 months after Transplant 1: Melphalan 100 mg/m2 days -1 and -2

Maintenance

Intervention Type: DRUG

3 months after Transplant 2: Intron A 3 X 10\^6 units /m2 M-W-F subcutaneously until relapse

Interventions

VAD

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

Intervention Type: DRUG

High-Dose cyclophosphamide

Approximately 5-6 weeks after VAD 2 or 3:

Cytoxan 1.2g/m2/d d 1 - 5 Mesna 3.6 g/m2 d 1

Intervention Type: DRUG

Hemopoietic stem cell procurement

Collection target = 10 x 10\^6 cells/kg

Intervention Type: PROCEDURE

EDAP

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

Intervention Type: DRUG

Autologous Hemopoietic Stem Cell Transplant 1

4-6 weeks after EDAP: Melphalan 100 mg/m2 days -1 and -2

Intervention Type: PROCEDURE

Autologous Hemopoietic Stem Cell Transplant 2

4-6 months after Transplant 1: Melphalan 100 mg/m2 days -1 and -2

Intervention Type: PROCEDURE

Maintenance

3 months after Transplant 2: Intron A 3 X 10\^6 units /m2 M-W-F subcutaneously until relapse

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.
• 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).

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Arkansas

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bart Barlogie, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Arkansas

Locations

University of Arkansas for Medical Sciences/MIRT

Little Rock, Arkansas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 40471585 (View on PubMed)

Other Identifiers

01332

Identifier Type: -

Identifier Source: org_study_id