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Sequential High-Dose Melphalan and Busulfan/Cyclophosphamide Followed by Peripheral Blood Progenitor Cell Rescue, Interferon/Thalidomide and Pamidronate for Patients With Multiple Myeloma


Phase 2
N/A
65 Years
Open (Enrolling)
Both
Multiple Myeloma and Plasma Cell Neoplasm

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Trial Information

Sequential High-Dose Melphalan and Busulfan/Cyclophosphamide Followed by Peripheral Blood Progenitor Cell Rescue, Interferon/Thalidomide and Pamidronate for Patients With Multiple Myeloma


OBJECTIVES:

- Determine the feasibility and toxic effects of high-dose melphalan, busulfan, and
cyclophosphamide followed by autologous peripheral blood stem cell rescue, interferon
alfa, and pamidronate in patients with responsive or stable, low-bulk multiple myeloma.

- Determine the response rate and progression-free and overall survival of patients
treated with this regimen.

- Determine the feasibility of adding thalidomide to interferon alfa and pamidronate in
patients who are not in complete remission (CR) 6 months after the second course of
high-dose chemotherapy.

- Determine whether administration of thalidomide can increase the CR rate in patients
who are not in CR 6 months after the second course of high-dose chemotherapy and
determine its effect on progression-free and overall survival of these patients.

- Determine the pharmacokinetics of busulfan and cyclophosphamide and correlate the
pharmacokinetics with the toxic effects of these drugs and outcome in these patients.

- Determine the effect of thalidomide on microvascular density of bone marrow and
correlate these possible effects with outcome in these patients.

- Determine the cytogenetics, gene rearrangement, and fluorescence in situ hybridization
in baseline and post treatment bone marrow and blood specimens and correlate the
presence/persistence of these features with treatment outcome in these patients.

OUTLINE: Patients receive cyclophosphamide IV over 2 hours on day 1 and filgrastim (G-CSF)
subcutaneously (SC) or IV twice a day beginning on day 2 and continuing until peripheral
blood stem cells (PBSCs) are collected. PBSCs are collected beginning on day 10.

Patients receive high-dose melphalan IV on day -1. PBSCs are reinfused on day 0. G-CSF is
administered IV or SC daily beginning on day 1 and continuing until blood counts recover.
Between 8 and 14 weeks later, patients receive high-dose busulfan IV every 6 hours on days
-7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. PBSCs are reinfused on day
0 and G-CSF is administered IV or SC daily until blood counts recover.

Patients with responding or stable disease after chemotherapy receive maintenance therapy
with interferon alfa beginning 14-20 weeks after day 0 of the second course of chemotherapy.
Interferon alfa is administered SC 3 times a week for 3 years. Patients also receive
pamidronate IV every 4 weeks until disease progression. Patients who are not in complete
remission (CR) 6 months after completing the second course of chemotherapy receive oral
thalidomide daily for a maximum of 1 year or for 3 months after achieving CR.

Patients are followed monthly for 1 year, every 3 months for 1 year, and then periodically
thereafter.

PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study within
approximately 2.5 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically proven stage I-III multiple myeloma

- Less than 18 months since diagnosis

- Smoldering myeloma allowed if there is evidence of progressive disease requiring
therapy

- At least 25% increase in M protein levels or Bence Jones excretion

- Hemoglobin no greater than 10.5 g/dL

- Hypercalcemia

- Frequent infections

- Rise in serum creatinine above normal on 2 separate occasions

- Nonquantifiable monoclonal proteins allowed if other criteria for multiple
myeloma or smoldering myeloma are met

- Response/status after induction therapy:

- Responding or stable disease AND no greater than 40% myelomatous involvement of
bone marrow

- No Waldenstrom's macroglobulinemia

PATIENT CHARACTERISTICS:

Age:

- 65 and under

Performance status:

- Karnofsky 80-100%

Life expectancy:

- Not specified

Hematopoietic:

- See Disease Characteristics

- Absolute neutrophil count greater than 1,500/mm^3

- Platelet count greater than 100,000/mm^3

Hepatic:

- Bilirubin no greater than 1.5 mg/dL

- SGOT and SGPT less than 2.5 times upper limit of normal

- Hepatitis B antigen or hepatitis C RNA negative

Renal:

- See Disease Characteristics

- Creatinine no greater than 1.4 mg/dL

- Creatinine clearance greater than 65 mL/min

Cardiovascular:

- Cardiac ejection fraction at least 50% by MUGA or echocardiogram

Pulmonary:

- FEV_1 greater than 60%

- DLCO greater than 50% of predicted lower limit

Other:

- Not pregnant

- Negative pregnancy test

- Fertile patients must use effective contraception

- HIV negative

- No other medical or psychosocial problems that would increase patient risk

- No other malignancy within past 5 years except nonmelanomatous skin cancer or
carcinoma in situ of the cervix

- No known hypersensitivity to filgrastim (G-CSF) or E. coli-derived proteins

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- Not specified

Chemotherapy:

- See Disease Characteristics

- No more than 3 prior chemotherapy regimens

- At least 4 weeks since prior chemotherapy

Endocrine therapy:

- Not specified

Radiotherapy:

- At least 4 weeks since prior radiotherapy

Surgery:

- Not specified

Type of Study:

Interventional

Study Design:

Masking: Open Label, Primary Purpose: Treatment

Principal Investigator

George Somlo, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

City of Hope Medical Center

Authority:

United States: Federal Government

Study ID:

99021

NCT ID:

NCT00004088

Start Date:

April 1999

Completion Date:

Related Keywords:

  • Multiple Myeloma and Plasma Cell Neoplasm
  • stage I multiple myeloma
  • stage II multiple myeloma
  • stage III multiple myeloma
  • Neoplasms
  • Multiple Myeloma
  • Neoplasms, Plasma Cell
  • Plasmacytoma

Name

Location

City of Hope Comprehensive Cancer CenterDuarte, California  91010
Banner Good Samaritan Medical CenterPhoenix, Arizona  85006