Melphalan, Total Marrow Irradiation, and Autologous Stem Cell Transplantation in Treating Patients With High-Risk Multiple Myeloma

NCT03100877 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: 16464NCI-2017-00512
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial studies the side effects and best dose of melphalan and total marrow irradiation and how well they work with autologous stem cell transplantation in treating patients with high-risk multiple myeloma. Drugs used in chemotherapy, such as melphalan, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Total marrow irradiation is a type of radiation therapy and a form of total body irradiation that may deliver focused radiation to the major marrow sites where cancer cells reside. Giving chemotherapy and total-body irradiation before a peripheral autologous blood stem cell transplant helps kill any cancer cells that are in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.

Conditions

Plasma Cell Leukemia in Remission; Plasma Cell Myeloma

Outcome Measures

Primary Outcomes (2)

• Complete Response (CR) post-Autologous Stem Cell Transplantation (ASCT) (Phase II)

  Will be summarized both by pooling across dose levels and by dose level.

  Up to 3 years

• Maximum Tolerated Dose (MTD) of mel/TMI (Phase I)

  Toxicity information recorded will include the type, severity, and the probable association with the study regimen. Tables will be constructed to summarize the observed incidence by severity and type of toxicity.

  Up to 3 years

Study Arms (1)

Treatment (mel/TMI, ASCT)

EXPERIMENTAL

MOBILIZATION AND APHERESIS: Patients receive cyclophosphamide IV over 2 hours. Beginning 24 hours after cyclophosphamide administration, patients receive filgrastim SC or IV. Patients also undergo apheresis over 4 hours on day 10. CONDITIONING REGIMEN: Patients receive palifermin IV on days -8, to -6, undergo TMI on days -5 to -2, and receive melphalan IV over 30 minutes on day -1. Patients then undergo ASCT IV on day 0, receive palifermin IV on days 1-3, and receive filgrastim SC or IV on day 5. MAINTENANCE THERAPY: Beginning 30 days after ASCT, patients receive lenalidomide PO daily.

Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Cyclophosphamide; Biological: Filgrastim; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Procedure: pheresis; Drug: Melphalan; Biological: Palifermin; Radiation: Total Marrow Irradiation

Interventions

Autologous Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo ASCT

Also known as: Autologous Stem Cell Transplantation

Treatment (mel/TMI, ASCT)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (mel/TMI, ASCT)

Filgrastim BIOLOGICAL

Given SC or IV

Also known as: Filgrastim XM02, Filgrastim-sndz, G-CSF, Neupogen, r-metHuG-CSF, Recombinant Methionyl Human Granulocyte Colony Stimulating Factor, rG-CSF, Tbo-filgrastim, Tevagrastim, Zarxio

Treatment (mel/TMI, ASCT)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (mel/TMI, ASCT)

Lenalidomide DRUG

Given PO

Also known as: CC-5013, CC5013, CDC 501, Revlimid

Treatment (mel/TMI, ASCT)

pheresis PROCEDURE

Undergo apheresis

Also known as: leukapheresis, Leukocytopheresis, Therapeutic Leukopheresis, apheresis

Treatment (mel/TMI, ASCT)

Melphalan DRUG

Given IV

Also known as: Alanine Nitrogen Mustard, CB-3025, L-PAM, L-Phenylalanine Mustard, L-Sarcolysin, L-Sarcolysin Phenylalanine mustard, L-Sarcolysine, Melphalanum, Phenylalanine Mustard, Phenylalanine Nitrogen Mustard, Sarcoclorin, Sarkolysin, WR-19813

Treatment (mel/TMI, ASCT)

Palifermin BIOLOGICAL

Given IV

Also known as: Growth Factor, Recombinant Human Keratinocyte, Kepivance, Keratinocyte Growth Factor, Recombinant Human, Recombinant Human Keratinocyte Growth Factor, rhKGF, rhu Keratinocyte Growth Factor

Treatment (mel/TMI, ASCT)

Total Marrow Irradiation RADIATION

Undergo TMI

Treatment (mel/TMI, ASCT)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with will be eligible if they are either in partial response, or have stable disease after no more than two attempts of induction therapy
• Patients with high-risk cytogenetics, t(4:14); t(14;16), t(14:20), deletion p17, gain in 1q, are eligible
• Patients with plasma cell leukemia in \>= partial remission are eligible
• Patients with non-quantifiable monoclonal proteins are eligible provided they meet other criteria for multiple myeloma and they have evaluable or measurable disease by other (radiographic, magnetic resonance imaging \[MRI\], computed tomography \[CT\], lytic measurable lesion on x-ray,) means
• Karnofsky performance status (KPS) \>= 70%
• Less than 12 months since diagnosis
• No contraindication to the collection of a minimum of 4 x 10\^6 CD34+ cells/kg by apheresis
• Bilirubin =\< 1.5 mg/dl
• Serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) \< 2.5 x upper limits of normal
• Creatinine of measured or calculated creatinine clearance of \>= 50 cc/min
• Absolute neutrophil count of \> 1000/ul
• Platelet count of \> 100,000/ul
• Cardiac ejection fraction \>= 50% by multi-gated acquisition (MUGA) scan and/or by echocardiogram
• Forced expiratory volume in 1 second (FEV1) \> 60% and diffusion capacity of the lung for carbon monoxide (DLCO) \> 50% of predicted lower limit
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately; patients must be fully aware of the teratogenic potential of immunomodulatory drugs (ImIDs) and agree to fully comply with the mandated guidelines regarding contraception as stated in the informed consent and the patient warning document attached to the consent form; women of childbearing potential must have a negative pregnancy test performed within 24 hours prior to beginning thalidomide, except for woman who have been postmenopausal for at least 2 years, or underwent hysterectomy; use of effective means of contraceptive should be started at least 2 weeks prior to initiating lenalidomide

You may not qualify if:

• Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in-situ malignancy, or low-risk prostate cancer after curative therapy
• Known hypersensitivity to filgrastim or to Escherichia coli (E. coli) derived proteins
• Inability to lie supine in a full body cast for approximately 30 minutes, the anticipated duration of each treatment session
• Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV); subjects who are positive for hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment; those who are PCR positive will be excluded
• No other medical, or psychosocial problems, which in the opinion of the primary physician or principal investigator would place the patient at unacceptably high risk from this treatment regimen

Sponsors & Collaborators

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

Study Sites (1)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Cyclophosphamide; Filgrastim; Granulocyte Colony-Stimulating Factor; Lenalidomide; Blood Component Removal; Leukapheresis; Melphalan; Fibroblast Growth Factor 7

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; 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)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; 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; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Therapeutics; Cytapheresis; Biological Therapy; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Fibroblast Growth Factors

Study Officials

• George Somlo, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2017
• First Posted: April 4, 2017
• Study Start: January 1, 2018
• Primary Completion: May 24, 2020
• Study Completion: May 24, 2020
• Last Updated: December 13, 2017

Record last verified: 2017-12

Locations

US (1)