Clinical trial NCT00670631: Tandem Transplantation in Multiple Myeloma (MM) Patients With <12 Months of Prior Treatment
Official title: Tandem Autotransplantation for Multiple Myeloma Patients With Less Than 12 Months of Preceding Therapy, Incorporating Bortezomib With the Transplant Chemotherapy and During Maintenance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Multiple Myeloma
myeloma
Lead sponsor: University of Iowa
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2008-05-02
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Induction- Tandem Transplants with VTD-MEL and gemcitabine, BCNU, melphalan, velcade and dexamethasone- Maintenance therapy
Primary purpose: TREATMENT

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.

Detailed description: This study is targeted towards patients who have been diagnosed with Multiple Myeloma and have had no prior autologous or allogeneic transplant. Furthermore, only up to 12 months of prior treatment are allowed in this patient population. The study schema consists of one round of induction chemotherapy, two transplants, one round of consolidation chemotherapy, and two years of maintenance treatment. This study design differs from its historical predecessors in the following manner:

* In contrast to Total Therapy II and III, which only allow enrollment of patients with at most one cycle or one month of treatment prior to enrollment, the proposed study allows enrollment of patients with up to 12 months of prior treatment. No statistically significant difference in outcome between patients with one or no cycle of preceding therapy and those with up to 12 months of prior therapy. This should allow enrollment of significantly more myeloma patients.
* Induction therapy has been reduced to a single cycle.
* Bortezomib and thalidomide have been added to the transplant regimen.
* BCNU is added to the second transplant to high dose melphalan.
* Gemcitabine is added to the second transplant regimen.
* Consolidation treatment has been reduced to a single cycle.
* The first year of maintenance is with bortezomib, thalidomide and dexamethasone, and the second year of maintenance therapy consists of dexamethasone only.
* The novel agents thalidomide and bortezomib are not introduced upfront, but only with transplantation and maintenance.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. 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.
3. 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.
4. Patients must be 18-75 years of age at the time of initial registration.
5. Ejection fraction by ECHO or MUGA ≥ 40% performed within 60 days prior to registration.
6. 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.
7. Patients must have a creatinine \< 3 mg/dl and a creatinine clearance \>30mL/min
8. 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.
9. 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.

Exclusion Criteria:

1. Platelet count \< 30 x 109/L, unless myeloma-related.
2. Greater than a grade 2 peripheral neuropathy.
3. Hypersensitivity to bortezomib, boron, or mannitol.
4. Uncontrolled diabetes.
5. Recent (\< 6 months) myocardial infarction, unstable angina, difficult to control congestive heart failure, uncontrolled hypertension, or difficult to control cardiac arrhythmias.
6. Evidence of chronic obstructive or chronic restrictive pulmonary disease.
7. Patients must not have light chain deposition disease-related renal failure or creatinine \> 3 mg/dl.
8. 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.
9. Patients must not have significant co-morbid medical conditions or uncontrolled life threatening infection.
10. 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.

Primary outcomes:
measure: 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%
timeFrame: After enrollment of 204 subjects is completed
measure: 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%.
timeFrame: Interim analyses for safety will be performed after 20, 100, 200, and 300 patients have been enrolled.
Secondary outcomes:
measure: Overall Survival Will be Compared to a Historical Control (UARK 98-026, TT2)as a Secondary Outcome.
timeFrame: After 204 patients have been enrolled
Other outcomes:
Locations:
Study officials:
affiliation: University of Iowa
name: Guido J Tricot, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: