Combination Chemo, Peripheral Stem Cell Transplant, Biological Therapy, Pamidronate and Thalidomide for Multiple Myeloma

NCT00004088 | Completed Phase 2 Results

• 5 other identifiers: 99021P30CA033572CHNMC-IRB-99021NCI-G99-1583CDR0000067301
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Multiple Myeloma and Plasma Cell Neoplasm

Keywords

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

Outcome Measures

Primary Outcomes (6)

• 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.

  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.

  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.

  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.

  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.

  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.

  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.

Study Arms (1)

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.

Biological: filgrastim; Biological: recombinant interferon alfa; Drug: busulfan; Drug: cyclophosphamide; Drug: melphalan; Drug: pamidronate disodium; Drug: thalidomide; Procedure: peripheral blood stem cell transplantation

Interventions

filgrastim BIOLOGICAL

Also known as: granulocyte colony-stimulating factor (G-CSF), Neupogen

HD chemotherapy followed by PBPC Rescue

recombinant interferon alfa BIOLOGICAL

Also known as: IFN alpha-2B, Intron A

HD chemotherapy followed by PBPC Rescue

busulfan DRUG

Also known as: Myleran, Busulfex

HD chemotherapy followed by PBPC Rescue

cyclophosphamide DRUG

Also known as: cytophosphane, Cytoxan

HD chemotherapy followed by PBPC Rescue

melphalan DRUG

Also known as: Alkeran, Evomela

HD chemotherapy followed by PBPC Rescue

pamidronate disodium DRUG

Also known as: pamidronic acid

HD chemotherapy followed by PBPC Rescue

thalidomide DRUG

Also known as: Thalidomid, Immunoprin

HD chemotherapy followed by PBPC Rescue

peripheral blood stem cell transplantation PROCEDURE

Also known as: peripheral blood progenitor cell transplantation

HD chemotherapy followed by PBPC Rescue

Eligibility Criteria

• Age: Up to 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Banner Good Samaritan Medical Center

Phoenix, Arizona, 85006, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010-3000, United States

Location

Related Publications (1)

• 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.

  BACKGROUND

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Filgrastim; Granulocyte Colony-Stimulating Factor; Interferon-alpha; Introns; Busulfan; Cyclophosphamide; Melphalan; Pamidronate; Thalidomide; Peripheral Blood Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Interferon Type I; Interferons; DNA, Intergenic; Genome Components; Genome; Genetic Structures; Genetic Phenomena; Gene Components; Genes; Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Diphosphonates; Organophosphonates; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Brenda Williams, Senior Director, Clinical Trials Office
• Organization: City of Hope

bwilliams@coh.org

626-218-2702

Study Officials

• George Somlo, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 1999
• First Posted: January 27, 2003
• Study Start: April 13, 1999
• Primary Completion: January 9, 2018
• Study Completion: January 9, 2018
• Last Updated: July 2, 2019
• Results First Posted: July 2, 2019

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)