Multiple Myeloma and Plasma Cell NeoplasmPhase 2NCT00004088
Combination Chemo, Peripheral Stem Cell Transplant, Biological Therapy, Pamidronate and Thalidomide for Multiple Myeloma
A Phase 2 study testing filgrastim, recombinant interferon alfa and busulfan in people with Multiple Myeloma and Plasma Cell Neoplasm, run by City of Hope Medical Center at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages Up to 65 years
- Conditions the study is for
- Multiple Myeloma and Plasma Cell Neoplasm
- What is being tested?
- filgrastim, recombinant interferon alfa and busulfan
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 77 participants
- Where
- 2 sitesUnited States
- Study dates
- 13 Apr 1999to 9 Jan 2018
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
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
- Serum glutamic axaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) less than 2.5 times upper limit of normal
- Hepatitis B antigen or hepatitis C ribonucleaic acid (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 multigated acquisition scan (MUGA) or echocardiogram
Pulmonary:
- Forced-expiratory volume in one second (FEV_1) greater than 60% of normal
- Diffusing capacity for carbon monoxide (DLCO) greater than 50% of predicted lower limit
Other:
- Not pregnant
- Negative pregnancy test
- Fertile patients must use effective contraception
- Human immunodeficiency virus (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 Escherechi 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
City of Hope Comprehensive Cancer Center
Duarte, California, 91010-3000
Banner Good Samaritan Medical Center
Phoenix, Arizona, 85006
About this study
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
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.
Read the 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.
- Being tested
- filgrastim, recombinant interferon alfa, busulfan, cyclophosphamide, melphalan
- Keywords
- stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma
- Medical subject headings
- Multiple Myeloma, Neoplasms, Plasma Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
filgrastimBiological
Also called granulocyte colony-stimulating factor (G-CSF), Neupogen
recombinant interferon alfaBiological
Also called IFN alpha-2B, Intron A
busulfanDrug
Also called Myleran, Busulfex
cyclophosphamideDrug
Also called cytophosphane, Cytoxan
melphalanDrug
Also called Alkeran, Evomela
pamidronate disodiumDrug
Also called pamidronic acid
thalidomideDrug
Also called Thalidomid, Immunoprin
peripheral blood stem cell transplantationProcedure or surgery
Also called peripheral blood progenitor cell transplantation
| Study group | Role | What they receive |
|---|---|---|
| HD chemotherapy followed by PBPC Rescue | Experimental | Patients receive high-dose (HD) melphalan intra-venously (IV) on day -1. Peripheral blood progenitor cells (PBPCs) are reinfused on day 0. Filgrastim (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 IV high-dose busulfan every 6 hours on days -7 to -4 and cyclophosphamide IV over 2 hours on days -3 and -2. PBPCs are reinfused on day 0 and G-CSF is administered IV or subcutaneously (SC) daily until blood counts recover. Receives: Biological: filgrastim; Biological: recombinant interferon alfa; Drug: busulfan; Drug: cyclophosphamide; Drug: melphalan; Drug: pamidronate disodium; Drug: thalidomide; Procedure: peripheral blood stem cell transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Best Response Prior to Tandem Autologous Stem Cell Transplant
Response gradations are specified in the "Blade criteria", Br J Haematol 1998; 102: 1115-1123. Serum myeloma protein is measured 2x at least six weeks apart, and urine M-component is measured 2x at least 3 weeks apart. Complete response (CR): less than 3% plasma cells in bone marrow or blood. Very good partial response (VGPR): Greater than 90% decrease in myeloma protein, and urine M-component less than 0.1 gm/day. Partial response (PR) Greater than 50% decrease in myeloma protein; urine M-component less than 0.2 gm/day. Lytic skeletal lesions must not increase, and serum calcium level must remain normal. Stable disease (SD): 25-49% decrease in protein and 25% decrease in urine M-component. Progressive disease (PD): Greater than 25% increase in myeloma protein, or hypercalcemia. Relapse: 1) increase greater than 100% of myeloma protein; 2) More than 25% increase of myeloma protein; 3) reappearance of the myeloma peaks; 4) increase in lytic bone lesions on radiographs.
Measured: From enrollment in the study until day -8: before dilantin given pre-first high-dose chemo preceeding first cycle of tandem autologous cell transplant
Response After Tandem Autologous Stem Cell Transplant
Response gradations are specified in the "Blade criteria", Br J Haematol 1998; 102: 1115-1123. Serum myeloma protein is measured 2x at least six weeks apart, and urine M-component is measured 2x at least 3 weeks apart. Complete response (CR): less than 3% plasma cells in bone marrow or blood. Very good partial response (VGPR): Greater than 90% decrease in myeloma protein, and urine M-component less than 0.1 gm/day. Partial response (PR) Greater than 50% decrease in myeloma protein; urine M-component less than 0.2 gm/day. Lytic skeletal lesions must not increase, and serum calcium level must remain normal. Stable disease (SD): 25-49% decrease in protein and 25% decrease in urine M-component. Progressive disease (PD): Greater than 25% increase in myeloma protein, or hypercalcemia. Relapse: 1) increase greater than 100% of myeloma protein; 2) More than 25% increase of myeloma protein; 3) reappearance of the myeloma peaks; 4) increase in lytic bone lesions on radiographs.
Measured: After second cycle of tandem autologous stem cell transplant: Day 0 of second transplant to 12 weeks post-cycle 2 cell infusion of the tandem transplant.
Three-year Overall Survival
Kaplan-Meier estimate at three years post-first transplant of survival. Outcome is death or alive at follow-up (censored). 95 percent confidence interval of the point estimate is calculated using Greenwood's variance.
Measured: Estimate reported at three years after day 0 of the first cycle of infusion of cells of the tandem transplant.
Progression-free Survival
Kaplan-Meier estimate at three years post-first transplant of survival. Event of interest is the first of Death or Progression. Censoring is Alive in Continuous Complete Remission at date of last follow-up.
95 percent confidence interval of the point estimate is calculated using Greenwood's variance.
Measured: Estimate reported at three years after day 0 of the first cycle of infusion of cells of the tandem transplant.
Best Response at 6 Months Post Tandem Autologous Stem Cell Transplant
Response gradations are specified in the "Blade criteria", Br J Haematol 1998; 102: 1115-1123. Serum myeloma protein is measured 2x at least six weeks apart, and urine M-component is measured 2x at least 3 weeks apart. Complete response (CR): less than 3% plasma cells in bone marrow or blood. Very good partial response (VGPR): Greater than 90% decrease in myeloma protein, and urine M-component less than 0.1 gm/day. Partial response (PR) Greater than 50% decrease in myeloma protein; urine M-component less than 0.2 gm/day. Lytic skeletal lesions must not increase, and serum calcium level must remain normal. Stable disease (SD): 25-49% decrease in protein and 25% decrease in urine M-component. Progressive disease (PD): Greater than 25% increase in myeloma protein, or hypercalcemia. Relapse: 1) increase greater than 100% of myeloma protein; 2) More than 25% increase of myeloma protein; 3) reappearance of the myeloma peaks; 4) increase in lytic bone lesions on radiographs.
Measured: Six months after day 0 of the first cycle of the tandem autologous stem cell transplant. This will be used to determine administration of thalidomide.
Best Response After Tandem Autologous Stem Cell Transplant and Maintenance
Response gradations are specified in the "Blade criteria", Br J Haematol 1998; 102: 1115-1123. Serum myeloma protein is measured 2x at least six weeks apart, and urine M-component is measured 2x at least 3 weeks apart. Complete response (CR): less than 3% plasma cells in bone marrow or blood. Very good partial response (VGPR): Greater than 90% decrease in myeloma protein, and urine M-component less than 0.1 gm/day. Partial response (PR) Greater than 50% decrease in myeloma protein; urine M-component less than 0.2 gm/day. Lytic skeletal lesions must not increase, and serum calcium level must remain normal. Stable disease (SD): 25-49% decrease in protein and 25% decrease in urine M-component. Progressive disease (PD): Greater than 25% increase in myeloma protein, or hypercalcemia. Relapse: 1) increase greater than 100% of myeloma protein; 2) More than 25% increase of myeloma protein; 3) reappearance of the myeloma peaks; 4) increase in lytic bone lesions on radiographs.
Measured: Response after six months after day 0 of the first cycle of the tandem transplant, after administration of maintenance thalidomide if necessary, until three years post-day 0 of the first cycle of the tandem transplant.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2003 (estimated)
- Study start13 Apr 1999
- Primary completion9 Jan 2018
- Study completion9 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple Myeloma and Plasma Cell NeoplasmStudies of the same condition, open and under way.
- More trials run by City of Hope Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- City of Hope Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- George Somlo, MD, Principal investigator, City of Hope Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00004088
- Sponsor's protocol ID
- 99021
- Other IDs
- P30CA033572, CHNMC-IRB-99021, NCI-G99-1583, CDR0000067301
- Status last verified
- Jan 2018
- First submitted
- 10 Dec 1999
- Last updated
- 2 Jul 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Individual data sharing
- No
Publications
Long-term Progression-free (PFS) and Overall Survival (OS) with Tandem Autologous Transplant (TASCT) After High-dose Induction With Melphalan (MEL) and Busulfan/cyclophosphamide (BU/CY), or a Novel Regimen of MEL and Total Marrow Irradiation (TMI), Followed by Maintenance With Interferon A-2 (IF) and/or Thalidomide (THAL). Haematologica 96(s1), 2011, s103. G. Somlo, J. Palmer, A. Dagis, M. O'Donnell, D. Snyder, F. Sahebi, N. Kogut, A. Brown, R. Spielberger, P.Parker, C. Karanes, L. Popplewell, A. Stein, A. Krishnan, J. Alvarnas, J. Wong, S. Forman.