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

8. mars 2017 oppdatert av: 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

Studieoversikt

Status

Avsluttet

Forhold

Intervensjon / Behandling

Detaljert 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.

Studietype

Intervensjonell

Registrering (Faktiske)

1

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiesteder

  • Forente stater
    • Michigan
      • Detroit, Michigan, Forente stater, 48201
        • Barbara Ann Karmanos Cancer Institute

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år til 70 år (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

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

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: 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.
Annen: laboratoriebiomarkøranalyse
Korrelative studier
Legemiddel: fludarabin fosfat
Gitt IV
Andre navn:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Annen: farmakologisk studie
Korrelative studier
Andre navn:
  • farmakologiske studier
Legemiddel: bortezomib
Gitt IV
Andre navn:
  • MLN341
  • LDP 341
  • VELCADE
Legemiddel: sirolimus
Gitt PO
Andre navn:
  • Rapamune
  • AY 22989
  • rapamycin
  • SLM
Legemiddel: busulfan
Gitt IV
Andre navn:
  • BSF
  • BU
  • Misulfan
  • Mitosan
  • Myeloleukon
Biologisk: anti-tymocyttglobulin
Gitt IV
Andre navn:
  • ATGAM
  • ATG
  • Thymoglobulin
  • lymfocytt immunglobulin
Fremgangsmåte: allogen hematopoetisk stamcelletransplantasjon
Gjennomgå allogen HSCT
Legemiddel: takrolimus
Gitt IV
Andre navn:
  • Prograf
  • FK 506

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
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: Inntil 2 år etter transplantasjon
Inntil 2 år etter transplantasjon
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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Barbara Ann Karmanos Cancer Institute

Samarbeidspartnere

National Cancer Institute (NCI)

Etterforskere

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

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart

1. februar 2012

Primær fullføring (Faktiske)

1. mai 2013

Studiet fullført (Faktiske)

1. mai 2013

Datoer for studieregistrering

Først innsendt

13. februar 2012

Først innsendt som oppfylte QC-kriteriene

15. februar 2012

Først lagt ut (Anslag)

16. februar 2012

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

5. april 2017

Siste oppdatering sendt inn som oppfylte QC-kriteriene

8. mars 2017

Sist bekreftet

1. mars 2017

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

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

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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