UARK 98-026 TT II: Multiple Myeloma Evaluating Anti-Angiogenesis With Thalidomide and Post-Transplant Consolidation Chemotherapy

University of Arkansas

Status and phase: Completed; Phase 3

Conditions: Multiple Myeloma

Treatments: Drug: Melphalan; Drug: Cisplatin; Drug: Interferon-alpha-2b; Drug: Thalidomide; Drug: Dexamethasone; Drug: Vincristine; Drug: Doxorubicin; Drug: BCNU; Drug: Recombinant GM-CSF; Drug: Filgrastim; Drug: Etoposide; Drug: Ara-C; Drug: Cytoxan

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00083551

5226

Details and patient eligibility

About

This study has been designed to evaluate whether "anti-angiogenesis" therapy with thalidomide and whether additional chemotherapy after transplant will be beneficial. Another objective is to find out what kinds of side effects occur with this combination of treatment and how often they occur.

Full description

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.

Enrollment: 668 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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668 participants in 2 patient groups

Thalidomide

Active Comparator group

Description:

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

Treatment:

Drug: Cytoxan

Drug: Cisplatin

Drug: Ara-C

Drug: Dexamethasone

Drug: Etoposide

Drug: Filgrastim

Drug: BCNU

Drug: Interferon-alpha-2b

Drug: Recombinant GM-CSF

Drug: Thalidomide

Drug: Melphalan

No Thalidomide

Active Comparator group

Description:

During induction, consolidation, and maintenance steps patient receives no thalidamide

Treatment:

Drug: Cytoxan

Drug: Cisplatin

Drug: Ara-C

Drug: Dexamethasone

Drug: Etoposide

Drug: Filgrastim

Drug: BCNU

Drug: Doxorubicin

Drug: Vincristine

Drug: Interferon-alpha-2b

Drug: Recombinant GM-CSF

Drug: Melphalan