Combination Chemotherapy, Peripheral Stem Cell Transplantation, Biological Therapy, Pamidronate and Thalidomide in Treating Patients With Multiple Myeloma - Full Text View

Sponsor:	City of Hope Medical Center
Collaborator:	National Cancer Institute (NCI)
Information provided by (Responsible Party):	City of Hope Medical Center
ClinicalTrials.gov Identifier:	NCT00004088

Purpose

RATIONALE: Drugs used in chemotherapy work in different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow doctors to give higher doses of chemotherapy drugs and kill more cancer cells. Biological therapies, such as interferon alfa, use different ways to stimulate the immune system and stop cancer cells from growing. Thalidomide may stop the growth of cancer cells by stopping blood flow to the tumor. Pamidronate may help to reduce the side effects of treatment for multiple myeloma.

PURPOSE: This phase II trial is studying combination chemotherapy, peripheral stem cell transplantation, biological therapy, pamidronate, and thalidomide to see how well they work in treating patients with stage I, stage II, or stage III multiple myeloma.

Condition	Intervention	Phase
Multiple Myeloma and Plasma Cell Neoplasm	Biological: filgrastim Biological: recombinant interferon alfa Drug: busulfan Drug: cyclophosphamide Drug: melphalan Drug: pamidronate disodium Drug: thalidomide Procedure: peripheral blood stem cell transplantation	Phase II

Study Type:	Interventional
Study Design:	Masking: Open Label Primary Purpose: Treatment
Official Title:	Sequential High-Dose Melphalan and Busulfan/Cyclophosphamide Followed by Peripheral Blood Progenitor Cell Rescue, Interferon/Thalidomide and Pamidronate for Patients With Multiple Myeloma

Resource links provided by NLM:

Further study details as provided by City of Hope Medical Center:

Study Start Date:	April 1999
Estimated Primary Completion Date:	October 2012 (Final data collection date for primary outcome measure)

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	up to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00004088

Locations

United States, Arizona
Banner Good Samaritan Medical Center
Phoenix, Arizona, United States, 85006
United States, California
City of Hope Comprehensive Cancer Center
Duarte, California, United States, 91010-3000

Sponsors and Collaborators

City of Hope Medical Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

George Somlo, MD

City of Hope Medical Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	City of Hope Medical Center
ClinicalTrials.gov Identifier:	NCT00004088 History of Changes
Other Study ID Numbers:	99021, P30CA033572, CHNMC-IRB-99021, NCI-G99-1583, CDR0000067301
Study First Received:	December 10, 1999
Last Updated:	October 14, 2011
Health Authority:	United States: Federal Government

Keywords provided by City of Hope Medical Center:

stage I multiple myeloma
stage II multiple myeloma
stage III multiple myeloma

Additional relevant MeSH terms:

Neoplasms
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

Interferon-alpha
Interferon Alfa-2a
Interferons
Busulfan
Cyclophosphamide
Melphalan
Thalidomide
Lenograstim
Pamidronate
Diphosphonates
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors

ClinicalTrials.gov processed this record on February 13, 2012