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

Summary

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.

Conditions

• Multiple Myeloma

Interventions

DRUG

Thalidomide

All patients will be randomly assigned to receive thalidomide 400 mg as an oral, once daily dose throughout induction and 100mg between transplants after platelets are greater than 50,000μl and 200 mg post transplant consolidation, and a reduced dose of 100 mg on alternating days during the first year of maintenance and 50 mg qod thereafter versus no thalidomide. Thalidomide will be held during conditioning, transplant procedure, and recovery following transplant. It may be resumed once plateletrecovery is complete after each transplant

DRUG

Ara-C

Cytarabine (Ara-C) 400 mg/m2 in 250 ml D5W over one hour daily for four days (on days -5, -4, -3, -2). Start infusion 30 minutes after completion of BCNU on day -5.

DRUG

BCNU

Carmustine (BCNU) 300 mg/m2 in 1 liter of D5W in glass bottle (protect from light) to infuse over 2 hours on day -5. Check blood pressure every 15 minutes during infusion and 30 minutes after completion

DRUG

Cisplatin

Cisplatin\* 15 mg/m2/day Continuous infusion 1-4 (DCEP CYCLE 2) Cisplatin\* 7.5 mg/m2 Continuous infusion 1-4 (DPACE cycle) \*Cisplatin doses will be modified for renal insufficiency as follows: Cisplatin dose Creatinine 15 mg/m2 (full dose) \< 1.5 mg/dl 10 mg/m2 1.6 - 2.0 mg/dl 7.5 mg/m2 2.1 - 3.0 mg/dl 0 mg (hold Cisplatin) \> 3.0 mg/dl

DRUG

Cytoxan

Cycle 2 - DCEP Cyclophosphamide 400 mg/m2/day Continuous infusion 1-4 Cycle 3 - CAD and PBSC Collection #1 Cyclophosphamide 750 mg/m2/day Continuous infusion 1-4 Cycle 4 - DCEP Cyclophosphamide 400 mg/m2/day Continuous infusion 1-4 Cytoxan/VP-16 and PBSC Collection-Cyclophosphamide 2 grams/m2 (Total dose 4 gm/m2) IV by CI 1 and 2 Post-Transplant Consolidation-Cyclophosphamide 300 mg/m2 Continuous infusion 1-4

DRUG

Dexamethasone

Induction cycle 1 VAD Dexamethasone 40 mg/day PO 1-4, 9-12, 17-20 Cycle 2 - DCEP Dexamethasone 40 mg/day PO 1-4 Cycle 3 - CAD and PBSC Collection #1 Dexamethasone 40 mg/day PO 1-4 Cycle 4 - DCEP and PBSC Collection #2 Dexamethasone 40 mg/day PO 1-4 Post-Transplant Consolidation Dexamethasone 40 mg PO 1-4 Dexamethasone Consolidation Patients that do not achieve adequate platelet recovery (defined as \< 80,000/μl) will receive consolidation with Dexamethasone 40 mg x 4 days every 28 days for 1 year Maintenance year one Dexamethasone 40 mg PO q 3 months, day 1-4, 9-12, 17-20

DRUG

Doxorubicin

Doxorubicin may be further diluted in 5% dextrose or sodium chloride injection and should be administered slowly into tubing of a freely flowing intravenous infusion with great care taken to avoid extravasation.

DRUG

Etoposide

Etoposide (VP16) 200 mg/m2 in 500 ml D5W over one hour daily for four days (on days -5, -4, -3, -2). Start infusion 30 minutes after completion of BCNU on day -5. Start infusion at completion of cytarabine on following three days

DRUG

Filgrastim

G-CSF will be administered at a dose of 10mcg/kg or GM-CSF at a dose of 10 mcg/kg. G-CSF or GM-CSF will begin one day after completion of chemotherapy and continued during repeated apheresis and discontinued upon completion of apheresis.

DRUG

Recombinant GM-CSF

GM-CSF at a dose of 10 μg/kg SC, divided in 2 doses each day, will begin one day after completion of chemotherapy and continued during repeated apheresis and discontinued upon completion of apheresis.

DRUG

Interferon-alpha-2b

AGENT DOSE ROUTE DAYS Intron-A 3 million units/m2 SQ TIW Thalidomide (for those randomized at initial registration) 50 mg QOD PO Every other day (qod

DRUG

Melphalan

Etoposide (VP16) 200 mg/m2 in 500 ml D5W over one hour daily for four days (on days -5, -4, -3, -2). Start infusion 30 minutes after completion of BCNU on day -5. Start infusion at completion of cytarabine on following three days

DRUG

Vincristine

Formulation: 1 mg/1 ml, 2 mg/2 ml, and 5 mg/ 5 ml vials. Vincristine should be administered intravenously through a freely-running IV. If it extravasates, it produces a severe local reaction with skin slough. FATAL IF GIVEN INTRATHECALLY, FOR INTRAVENOUS USE ONLY.

Sponsors & Collaborators

• Celgene Corporation

  collaborator INDUSTRY

• University of Arkansas

  lead OTHER

Principal Investigators

• Bart Barlogie, M.D., Ph.D. · UAMS

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

1998-08-31

Primary Completion

2014-08-31

Completion

2014-08-31

Countries

• United States

Study Locations