Tandem Auto Transplantation in Myeloma Patients With <12 Months of Prior Treatment

NCT01548573 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 2012028187R01CA115399
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This study is designed to decrease toxicity associated with prior tandem transplant protocols by reducing the intensity of induction, consolidation and maintenance therapy, while increasing event-free survival by adding bortezomib (Velcade®), thalidomide, gemcitabine and carmustine to the transplant regimens to down-regulate the rescue of myeloma cells by the micro-environment and to prevent DNA repair post high-dose alkylating agent therapy. By reducing drug resistance, it is hoped that 3-year event-free survival will be increased significantly when compared to Total Therapy II. Additionally, participants will have the option of providing biospecimens for a sub-study evaluating gene expression profiling at specific timepoints to better understand drug-resistance in myeloma, and to determine whether there are genes or gene products in the resistant population that can be targeted by novel therapies.

Conditions

Multiple Myeloma

Keywords

multiple myeloma; POEMS (Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes); amyloidosis; bone marrow transplant; autologous

Outcome Measures

Primary Outcomes (2)

• Event-Free Survival (EFS)

  To determine whether, in comparison to Total Therapy II, the median Event-Free Survival (EFS) can be increased from 4.8 years to 7.2 years, which represents an increase in median EFS of approximately 50%, based on an intent-to-treat analysis.

  8 years

• Identification of Drug Resistant Genes

  To determine whether repeated bone marrow samples analyzed for gene expression profiling (GEP) can identify genes related to drug resistance in myeloma. The drug resistant genes or the gene products might then be targeted specifically to eradicate myeloma cells surviving tandem transplantation.

  5 years

Secondary Outcomes (2)

• Number of Grade 3 Non-hematologic and Grade 4 Hematologic Serious Adverse Events Associated With the Addition of Bortezomib, Thalidomide, and Dexamethasone Into Autologous Transplant Regimens.

  2 years

• Overall Survival

  10 years

Study Arms (1)

Tandem autologous stem cell transplant

EXPERIMENTAL

Induction: DPACE(dexamethasone,cisplatin,doxorubicin,cyclophosphamide,etoposide) chemotherapy plus stem cell collection. Additional stem cell collection and/or chemotherapy may be required. After collection, participants will receive dexamethasone x 4 days every 14 days. Transplant 1: The transplant preparative regimen will be bortezomib/thalidomide/dexamethasone/melphalan. Once recovered, participants start thalidomide daily and dexamethasone x 4 days every 21 days. Consolidation (if administered): VDT-PACE(bortezomib,dexamethasone,thalidomide,cisplatin,doxorubicin,cyclophosphamide, etoposide) Transplant 2: 8 weeks to 6 months after the first transplant, participants will have the second transplant Maintenance: Year 1- VTD (bortezomib, thalidomide, dexamethasone) cycles. Year 2 - VCD (bortezomib, cyclophosphamide, dexamethasone)cycles.

Drug: Dexamethasone; Procedure: Tandem autologous stem cell transplant; Drug: Cisplatin; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Etoposide; Drug: Bortezomib; Drug: Thalidomide; Drug: Melphalan

Interventions

Dexamethasone DRUG

Given PO

Also known as: Aeroseb-Dex, Decaderm, Decadron, DM, DXM

Tandem autologous stem cell transplant

Tandem autologous stem cell transplant PROCEDURE

Tandem autologous stem cell transplant

Cisplatin DRUG

Given IV

Also known as: CACP, CDDP, CPDD, DDP

Tandem autologous stem cell transplant

Doxorubicin DRUG

Given IV

Also known as: ADM, ADR, Adria, Adriamycin PFS, Adriamycin RDF

Tandem autologous stem cell transplant

Cyclophosphamide DRUG

Given IV or PO

Also known as: CPM, CTX, Cytoxan, Endoxan, Endoxana

Tandem autologous stem cell transplant

Etoposide DRUG

Given IV

Also known as: EPEG, VP-16, VP-16-213, Vepesid

Tandem autologous stem cell transplant

Bortezomib DRUG

Given IV

Also known as: LDP 341, MLN341, VELCADE

Tandem autologous stem cell transplant

Thalidomide DRUG

Given PO

Also known as: Kevadon, Synovir, THAL, Thalomid

Tandem autologous stem cell transplant

Melphalan DRUG

Given IV

Also known as: Alkeran, CB-3025, L-PAM, L-phenylalanine mustard, L-Sarcolysin

Tandem autologous stem cell transplant

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have had a diagnosis of symptomatic MM, MM + amyloidosis, or POEMS (osteosclerotic myeloma: Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes) requiring treatment. Participants with a previous history of smoldering myeloma will be eligible if there is evidence of progressive disease requiring chemotherapy. Note that study participants do not need to have active disease at the time of study entry, as participants may have received up to 12 months of prior chemotherapy, which might have induced a response.
• Protein criteria must be present (quantifiable M-component of IgG, IgA, IgD, or IgE and/or urinary kappa or lambda light chain, Bence-Jones protein, or Free Kappa Light Chain or Free Lambda Light Chain) in order to evaluate response. Non-secretory participants are eligible provided the participant has \> 20% plasmacytosis OR multiple (\>3) focal plasmacytomas or focal lesions on MRI.
• Participants must have received no more than 12 months of prior chemotherapy for this disease. Participants may have received prior radiotherapy provided approval has been obtained from the PI.
• Participants must not have had a prior transplant.
• Participants must be 18-80 years of age at the time of study entry.
• Ejection fraction by ECHO or MUGA of ≥ 40% performed.
• Participants must have adequate pulmonary function studies, \> 50% of predicted on mechanical aspects (FEV1, FVC) and diffusion capacity (DLCO) \> 50% of predicted (adjusted for hemoglobin). If the participant is unable to complete pulmonary function tests due to disease related pain or condition, a participant may still be enrolled provided that the PI or enrolling investigator documents that the participant is a transplant candidate.
• Participants must have a creatinine \< 3 mg/dl and a calculated creatinine clearance \>30mL/min. The Cockroft-Gault equation may be used to obtain calculated creatinine clearance.
• Participants must have a performance status of 0-2 based on ECOG criteria. Participants with a poor performance status (3-4)based solely on bone pain will be eligible, provided there is documentation to verify this.
• Participants must sign the most current IRB-approved study ICF (Informed Consent Form).

You may not qualify if:

• Prior autologous or allogeneic transplant.
• Platelet count \< 30 x 109/L, unless myeloma-related. If MM-related, the enrolling investigator must document this.
• \> grade 3 neuropathy.
• Known hypersensitivity to bortezomib, boron, or mannitol.
• Uncontrolled diabetes.
• Recent (\< 6 months) myocardial infarction, unstable angina, difficult to control congestive heart failure, uncontrolled hypertension, or difficult to control cardiac arrhythmias.
• Participants must not have light chain deposition disease-related renal failure or creatinine \>3 mg/dl.
• Participants must not have a concurrent malignancy unless it can be adequately treated by surgical, non-chemotherapeutic intervention. Participants may have a history of prior malignancy, provided that he/she has not had any treatment within 365 days of study entry AND that life expectancy exceeds 5 years at the time of study entry.
• Participants must not have life-threatening co-morbidities.
• Women of child-bearing potential must have a documented negative pregnancy test documented within one week of study entry. Women and men of reproductive potential may not participate unless they have agreed, by signing the study ICF, to use effective contraceptive method(s) as outlined in that form.

Sponsors & Collaborators

• University of Iowa: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of Iowa Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Multiple Myeloma; Polyneuropathies; Endocrine System Diseases; Paraproteinemias; Amyloidosis

Interventions

Dexamethasone; Calcium Dobesilate; Cisplatin; Doxorubicin; Cyclophosphamide; Etoposide; Bortezomib; Thalidomide; Melphalan

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Boronic Acids; Acids, Noncarboxylic; Acids; Boron Compounds; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Limitations and Caveats

Enrollment halted prematurely. Study met stopping rules. Outcomes will not be tracked and published

Results Point of Contact

• Title: Guido Tricot, MD, PhD
• Organization: University of Iowa

guido-tricot@uiowa.edu

319-356-3425

Study Officials

• Guido J Tricot, MD, PhD

  University of Iowa

  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: PRINCIPAL INVESTIGATOR
• PI Title: Director, Holden Cancer Center Bone Marrow Transplant and Myeloma Program

Study Record Dates

• First Submitted: February 29, 2012
• First Posted: March 8, 2012
• Study Start: May 1, 2012
• Primary Completion: July 1, 2013
• Study Completion: August 1, 2014
• Last Updated: June 14, 2017
• Results First Posted: June 14, 2017

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)