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High Dose Busulfan and Bortezomib in Treating Patients With High Risk Multiple Myeloma Undergoing Stem Cell Transplant

8. marts 2017 opdateret af: Zaid Al-Kadhimi, Barbara Ann Karmanos Cancer Institute

A Pilot Study Using High Dose Busulfan and Bortezomib as Part of Allogeneic Transplant Conditioning Regimen for High Risk Multiple Myeloma Patients.

This pilot phase II trial studies how well giving high dose busulfan together with bortezomib works in treating patients with high risk multiple myeloma undergoing stem cell transplant. Drugs used in chemotherapy, such as busulfan, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cells growth. Giving busulfan together with bortezomib before a stem cell transplant may kill more cancer cells

Studieoversigt

Status

Afsluttet

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

PRIMARY OBJECTIVES:

I. To determine time to engraftment absolute neutrophil count (> 0.5 x 10^9/L for 3 consecutive days), and platelet (> 20X 109^/L for 3 consecutive days).

2. Incidence and severity of acute graft-versus-host disease (GVHD) using fludarabine (fludarabine phosphate) / busulfan / bortezomib preparative regimen and triple immune suppression with tacrolimus, sirolimus and Thymoglobulin (anti-thymocyte globulin).

3. To determine the safety related to this combination in the first six months post transplant, specifically, treatment related mortality and grade III and IV non hematologic toxicities, based on Common Terminology Criteria for Adverse Events (CTCAE) version 4 (v4).

SECONDARY OBJECTIVES:

I. Incidence of myeloma progression in this high risk group of patients.

II. Incidence of transplant related mortality and morbidity.

III. Incidence of thrombotic thrombocytopenic purpura (TTP) and sinusoidal obstructive syndrome (SOS).

IV. Incidence and severity of chronic GVHD.

V. Incidence of opportunistic infections including cytomegalovirus (CMV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV) reactivation.

I. Overall and progression free survival (PFS) at Day 100, 6 months, 1 & 2 years post transplant.

VII. To determine recovery of T-cell, B cell, and natural killer (NK) cell phenotypes post transplant.

OUTLINE:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -7 to -3, busulfan IV on days -6 to -3, and bortezomib IV on day -2.

GVHD PROPHYLAXIS: Patients receive anti-thymocyte globulin IV on days -3 to -1, sirolimus orally (PO) on day -3, and tacrolimus IV on day -3. Patients undergo allogeneic hematopoietic stem cell transplantation (HSCT) on day 0.

After completion of study treatment, patients are followed up for up to 2 years.

Undersøgelsestype

Interventionel

Tilmelding (Faktiske)

1

Fase

  • Fase 2

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

  • Forenede Stater
    • Michigan
      • Detroit, Michigan, Forenede Stater, 48201
        • Barbara Ann Karmanos Cancer Institute

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år til 70 år (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  • Ability to provide informed consent
  • Karnofsky Performance Status (KPS) >= 70
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Availability of a suitable allogeneic hematopoietic stem cell donor; minimum of human leukocyte antigen (HLA) 7/8 matched related or unrelated donor
  • High risk multiple myeloma with poor prognostic features based on having one or more of the following criteria:
  • Progressive disease after autologous transplant. No less than 3 months post auto transplant
  • Progressive or stable disease after induction chemotherapy using the most potent myeloma agents Lenalidomide and/or Bortezomib
  • Patients with high risk cytogenetic abnormalities documented on conventional cytogenetics or fluorescence in situ hybridization (FISH) (hypodiploidy, t(4:14), t(14:16) chromosome translocation, p53 and or complex cytogenetics) additionally, chromosome 13 deletion by standard cytogenetics
  • Negative beta-human chorionic gonadotropin (β-HCG) pregnancy test for women, as well as implementation of birth control for men and women

Exclusion Criteria:

  • Patients with prior allogeneic transplant, or more than one prior autologous transplant for any medical reason
  • Prior treatment with busulfan or gemtuzumab (Mylotarg ®) for any reason
  • Patient with history of allergy to boron, mannitol, or bortezomib
  • Creatinine clearance (CrCl) =< 50 ml/min
  • Ejection Fraction < 50%
  • Diffusion capacity of carbon monoxide (DLCO) < 50% predicted
  • Forced expiratory volume in 1 second (FEV1) < 50% predicted
  • Forced vital capacity (FVC) < 50% predicted
  • Patients with uncontrolled arrhythmia or uncontrolled heart disease at the screening time; patients with coronary heart disease (recent myocardial infarctions, angina, cardiac stent, or bypass surgery in the last 6 months) need to be cleared with a stress echo or nuclear myocardial perfusion stress test, and cardiology consult; all other cardiac history will be at the discretion of the principal investigator
  • Liver enzymes > 3 times upper limit normal
  • Bilirubin > 2 mg/dl (except Gilbert's disease)
  • International normalized ratio (INR) > 2
  • Any previous history of liver failure, hepatitis, or cirrhosis
  • Systemic Amyloidosis Known history of hepatitis B, C, human immunodeficiency virus (HIV) or any current uncontrolled infection
  • Grade > I neuropathy
  • Women who are pregnant or lactating
  • Current or history of alcohol or drug abuse
  • Use of other investigational agents within 30 days of enrollment to this study
  • Any patient with ascites
  • Any patient on home oxygen
  • Any clinical findings on history or physical exam which would in the opinion of the treating physician or principal investigator preclude the patient from participating in the study

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Interventionel model: Enkelt gruppeopgave
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Treatment (chemotherapy, enzyme inhibitor)

CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -7 to -3, busulfan IV on days -6 to -3, and bortezomib IV on day -2.

GVHD PROPHYLAXIS: Patients receive thymoglobulin IV on days -3 to -1, sirolimus PO on day -3, and tacrolimus IV on day -3. Patients undergo allogeneic HSCT on day 0.
Andet: laboratoriebiomarkøranalyse
Korrelative undersøgelser
Medicin: fludarabin fosfat
Givet IV
Andre navne:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Andet: farmakologisk undersøgelse
Korrelative undersøgelser
Andre navne:
  • farmakologiske undersøgelser
Medicin: bortezomib
Givet IV
Andre navne:
  • MLN341
  • LDP 341
  • VELCADE
Medicin: sirolimus
Givet PO
Andre navne:
  • Rapamune
  • AY 22989
  • rapamycin
  • SLM
Medicin: busulfan
Givet IV
Andre navne:
  • BSF
  • BU
  • Misulfan
  • Mitosan
  • Myeloleukon
Biologisk: anti-thymocyt globulin
Givet IV
Andre navne:
  • ATGAM
  • ATG
  • Thymoglobulin
  • lymfocyt immunglobulin
Procedure: allogen hæmatopoietisk stamcelletransplantation
Gennemgå allogen HSCT
Medicin: tacrolimus
Givet IV
Andre navne:
  • Prograf
  • FK 506

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Incidence and Severity of Acute GVHD Using Fludarabine Phosphate / Busulfan / Bortezomib Preparative Regimen and Triple Immune Suppression With Tacrolimus, Sirolimus and Anti-thymocyte Globulin
Tidsramme: First 6 months post-transplant
Graded using the Glucksberg scale. Proportions and confidence intervals will be estimated. Estimated using binary proportion estimates as well as competing risk method.
First 6 months post-transplant
Time to Platelet Absolute Neutrophil Recovery (Engraftment)
Tidsramme: First 6 months post-transplant
Estimated using Kaplan-Meier method.
First 6 months post-transplant
Treatment Related Mortality Defined as Death in Continuous or Complete Remission
Tidsramme: From the date of transplant to the date of death, assessed up to 6 months post transplant
Based on National Cancer Institute (NCI) CTCAE version 4.
From the date of transplant to the date of death, assessed up to 6 months post transplant
Grade III and IV Non Hematologic Toxicities
Tidsramme: First 6 months post transplant
Based on NCI CTCAE version 4.
First 6 months post transplant

Sekundære resultatmål

Resultatmål
Tidsramme
Samlet overlevelse
Tidsramme: Op til 2 år efter transplantation
Op til 2 år efter transplantation
Incidence of Myeloma Progression
Tidsramme: Time to the first observation of disease progression/relapse post transplant, assessed up to 2 years post transplant
Time to the first observation of disease progression/relapse post transplant, assessed up to 2 years post transplant
Incidence of Transplant Related Mortality and Morbidity
Tidsramme: Up to 2 years post transplant
Up to 2 years post transplant
Incidence of TTP
Tidsramme: Up to 2 years post transplant
Up to 2 years post transplant
Incidence of SOS
Tidsramme: Up to 2 years post transplant
Up to 2 years post transplant
Incidence and Severity of Chronic GVHD
Tidsramme: Up to 2 years post transplant
Up to 2 years post transplant
Incidence of Opportunistic Infections Including CMV, HSV, and EBV Reactivation
Tidsramme: Weekly to day 100
Weekly to day 100
Progression Free Survival
Tidsramme: From the day of transplant to progression, death, or last contact, assessed up to 2 years
From the day of transplant to progression, death, or last contact, assessed up to 2 years
Recovery of T-cell, B Cell and NK Cell Phenotypes
Tidsramme: Days 30, 60, 90, and at 6 months after transplant
Days 30, 60, 90, and at 6 months after transplant

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Barbara Ann Karmanos Cancer Institute

Samarbejdspartnere

National Cancer Institute (NCI)

Efterforskere

  • Ledende efterforsker: Zaid Al-Kadhimi, Barbara Ann Karmanos Cancer Institute

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart

1. februar 2012

Primær færdiggørelse (Faktiske)

1. maj 2013

Studieafslutning (Faktiske)

1. maj 2013

Datoer for studieregistrering

Først indsendt

13. februar 2012

Først indsendt, der opfyldte QC-kriterier

15. februar 2012

Først opslået (Skøn)

16. februar 2012

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

5. april 2017

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

8. marts 2017

Sidst verificeret

1. marts 2017

Mere information

Begreber relateret til denne undersøgelse

Yderligere relevante MeSH-vilkår

Andre undersøgelses-id-numre

  • 2011-151
  • NCI-2012-00120 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .

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