Tandem Transplantation in Multiple Myeloma (MM) Patients With <12 Months of Prior Treatment

NCT00670631 | Completed Phase 2 Results DMC

• 2 other identifiers: 250097R01CA115399
• Study Type: interventional
• Target: 46
• Locations: 0 countries
• Sites: N/A

Brief Summary

The two objectives of this study are:

• To increase the 2-year event-free survival from 55%, established with Total Therapy II (UARK 98-026), to 75% in myeloma patients with cytogenetic abnormalities, and from 80%, established with the Total Therapy II regimen, to 95% in myeloma patients without cytogenetic abnormalities.
• To determine whether bortezomib, thalidomide, and dexamethasone can be safely incorporated with transplant 1 into the established pre-transplant regimen of high-dose melphalan (used in Total Therapy II) and whether Velcade and gemcitabine can be safely added to the transplant 2 high-dose chemotherapy regimen of combination melphalan and BCNU.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; myeloma

Outcome Measures

Primary Outcomes (2)

• To Determine Whether, in Comparison to TT II, the Median EFS Can be Increased From 4.8 Years to 6.2 Years, Which Represents an Increase in Median EFS of Approximately 30%

  After enrollment of 204 subjects is completed

• In Assessing Patient Safety, we Will Examine Treatment Toxicity Related Mortality and SAEs. Historical Study Results Indicate That a Mortality Rate of Greater Than 10% is Not Acceptable in This Population, Nor is an SAE Rate of Greater Than 15%.

  Interim analyses for safety will be performed after 20, 100, 200, and 300 patients have been enrolled.

Secondary Outcomes (1)

• Overall Survival Will be Compared to a Historical Control (UARK 98-026, TT2)as a Secondary Outcome.

  After 204 patients have been enrolled

Study Arms (1)

Tandem autologous stem cell transplant

EXPERIMENTAL

Induction: DPACE(dexamethasone,cisplatin,doxorubicin,cyclophosphamide,etoposide) chemotherapy plus stem cell collection. Additional stem cell collection and/or chemotherapy may be required. After collection, participants will receive dexamethasone x 4 days every 14 days. Transplant 1: The transplant preparative regimen will be bortezomib/thalidomide/dexamethasone/melphalan. Once recovered, participants start thalidomide daily and dexamethasone x 4 days every 21 days. Consolidation (if administered): VDT-PACE(bortezomib,dexamethasone,thalidomide,cisplatin,doxorubicin,cyclophosphamide, etoposide) Transplant 2: 8 weeks to 6 months after the first transplant, participants will have the second transplant Maintenance: Year 1- VTD (bortezomib, thalidomide, dexamethasone) cycles. Year 2 - VCD (bortezomib, cyclophosphamide, dexamethasone)cycles.

Combination Product: tandem autologous transplantation

Interventions

tandem autologous transplantation COMBINATION_PRODUCT

DPACE: dexamethasone 20 mg days 1-4 and 8-11, cisplatin 10 mg/m2 days 1-4, Adriamycin 10 mg/m2 days 1-4, cyclophosphamide 400 mg/m2 days 1-4, etoposide 40 mg/m2 days 1-4. Transplant 1: Dexamethasone 20 mg days -4 to -1 and +2 to +5. Velcade 1mg/m2 on days -4,-1, +2, and +5. Thalidomide 100mg on day -4 to day +5. Melphalan, 100 mg/m2 on days -4 and -1. Transplant 2: Dexamethasone 20 mg on days -4 to -1 and +2 to +5. BCNU 300mg/m2 on day -4. Melphalan 140 mg/m2 on day -1. Velcade 1mg/m2 on days -4, -1, +2, +5. Gemcitabine 1000 mg/m2 on days -4 + -1. Maintenance year 1: Bortezomib 1.0 mg/m2 on days 1, 4, 15,18 every cycle. Thalidomide, 100 mg . Dexamethasone,20 mg,on days 1-4 \& 15-18 every cycle. Maintenance year 2: Dexamethasone, 20 mg,days 1-4 every cycle.

Tandem autologous stem cell transplant

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have the diagnosis of 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 M-component of IgG, IgA, IgD, or IgE and/or urinary kappa or lambda light chain, Bence-Jones protein, or Free Kappa Light Chain or Free Lambda Light Chain) 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.
• Patients must have received no more than 12 months of prior chemotherapy for this disease. Patients may have received prior radiotherapy provided approval has been obtained by the Principal Investigator.
• Patients must be 18-75 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) 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 creatinine \< 3 mg/dl and a creatinine clearance \>30mL/min
• 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.

You may not qualify if:

• Platelet count \< 30 x 109/L, unless myeloma-related.
• Greater than a 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-related renal failure 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.

Sponsors & Collaborators

• Guido Tricot: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Limitations and Caveats

Data not available. Study conducted at Utah. Upon PI leaving \& coming to Iowa, record was transferred to IA by ClinicalTrials.gov. No research activities under NCT00670631 were conducted at IA. PRS staff have corresponded and neither party have data.

Results Point of Contact

• Title: Guido Tricot, MD, PhD
• Organization: University of Iowa

guido-tricot@uiowa.edu

Study Officials

• Guido J Tricot, MD, PhD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Guido J.K. Tricot, MD, PhD

Model Details: Induction- Tandem Transplants with VTD-MEL and gemcitabine, BCNU, melphalan, velcade and dexamethasone- Maintenance therapy

Study Record Dates

• First Submitted: April 3, 2008
• First Posted: May 2, 2008
• Study Start: February 1, 2008
• Primary Completion: May 1, 2012
• Study Completion: April 1, 2014
• Last Updated: August 31, 2017
• Results First Posted: August 31, 2017

Record last verified: 2017-08