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Busulfan, Fludarabine, Donor Stem Cell Transplant, and Cyclophosphamide in Treating Patients With Multiple Myeloma or Myelofibrosis

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ClinicalTrials.gov Identifier: NCT03303950
Recruitment Status : Recruiting
First Posted : October 6, 2017
Last Update Posted : May 14, 2019
Sponsor:
Information provided by (Responsible Party):
University of Utah

Brief Summary:
This phase II trial studies how well busulfan, fludarabine, donor stem cell transplant, and cyclophosphamide in treating patients with multiple myeloma or myelofibrosis. Drugs used in chemotherapy, such as busulfan, fludarabine, and cyclophosphamide, 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. Giving chemotherapy before a donor stem cell transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Giving busulfan and fludarabine before and cyclophosphamide after donor stem cell may work better in treating patients with multiple myeloma or myelofibrosis.

Condition or disease Intervention/treatment Phase
Anemia ASXL1 Gene Mutation EZH2 Gene Mutation IDH1 Gene Mutation IDH2 Gene Mutation Plasma Cell Myeloma Primary Myelofibrosis Recurrent Plasma Cell Myeloma Secondary Myelofibrosis Thrombocytopenia Drug: Busulfan Drug: Cyclophosphamide Drug: Fludarabine Procedure: Hematopoietic Cell Transplantation Other: Laboratory Biomarker Analysis Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. To evaluate non-relapse mortality (NRM) up to day +100.

SECONDARY OBJECTIVES:

I. To evaluate non-relapse mortality (NRM) up to day +365. II. To evaluate the incidence of acute graft versus host disease (GVHD) and chronic GVHD up to day +365 post-transplant.

III. To evaluate the overall survival and disease free survival up to 1 year. IV. To evaluate clinical response and molecular response (complete response and partial response) up to 1 year.

OUTLINE:

Patients receive busulfan intravenously (IV) over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Patients undergo hematopoietic cell transplantation (HSCT) on day 0. Patients then receive cyclophosphamide IV over 60 minutes on days 3 and 4.

After completion of study treatment, patients are followed up for 1 year.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Allogeneic Stem Cell Transplantation for Multiple Myeloma and Myelofibrosis
Actual Study Start Date : January 29, 2018
Estimated Primary Completion Date : October 2022
Estimated Study Completion Date : October 2022


Arm Intervention/treatment
Experimental: Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)
Patients receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Patients undergo HSCT on day 0. Patients then receive cyclophosphamide IV over 60 minutes on days 3 and 4.
Drug: Busulfan
Given IV
Other Names:
  • 1, 4-Bis[methanesulfonoxy]butane
  • BUS
  • Bussulfam
  • Busulfanum
  • Busulfex
  • Busulphan
  • CB 2041
  • CB-2041
  • Glyzophrol
  • GT 41
  • GT-41
  • Joacamine
  • Methanesulfonic Acid Tetramethylene Ester
  • Methanesulfonic acid, tetramethylene ester
  • Mielucin
  • Misulban
  • Misulfan
  • Mitosan
  • Myeleukon
  • Myeloleukon
  • Myelosan
  • Mylecytan
  • Myleran
  • Sulfabutin
  • Tetramethylene Bis(methanesulfonate)
  • Tetramethylene bis[methanesulfonate]
  • WR-19508

Drug: Cyclophosphamide
Given IV
Other Names:
  • (-)-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

Drug: Fludarabine
Given IV
Other Name: Fluradosa

Procedure: Hematopoietic Cell Transplantation
Undergo HSCT
Other Names:
  • HCT
  • Hematopoietic Stem Cell Transplantation
  • HSCT
  • stem cell transplantation

Other: Laboratory Biomarker Analysis
Correlative studies




Primary Outcome Measures :
  1. Non-relapse mortality (NRM) [ Time Frame: Up to day 100 ]
    NRM is defined as death due to graft versus host disease, infections, sepsis, organ (lung, liver, kidney) toxicity. The outcome will be reported along with an exact binomial confidence intervals for informal comparison to the literature.


Secondary Outcome Measures :
  1. Cumulative incidence of clinical complete response and molecular complete response (complete response and partial response) [ Time Frame: Up to 1 year ]
  2. Disease free survival [ Time Frame: Up to 1 year ]
    Kaplan-Meier techniques will be used.

  3. Incidence of acute graft versus host disease (GVHD) [ Time Frame: Up to day 365 ]
    Will be done descriptively.

  4. Incidence of chronic GVHD [ Time Frame: Up to day 365 ]
    Will be assessed based on criteria established by the National Institutes of Health Consensus Development Project in 2005, and recently updated in 2014. Will be done descriptively.

  5. Non-relapse mortality [ Time Frame: Up to day 365 ]
    Will be done descriptively.

  6. Overall survival [ Time Frame: Up to 1 year ]
    Kaplan-Meier techniques will be used.

  7. Relapse rate [ Time Frame: Up to day 365 ]
    Will be done descriptively.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Patients must have one of the following diagnoses of multiple myeloma (MM) or primary/secondary myelofibrosis (MF)
  • Patients must have histologically documented multiple myeloma (MM)

    • Patients in early relapse (less than 24 months from initiation of systemic anti-myeloma therapy which may include single or planned tandem autologous transplant) after primary therapy that included and autologous HSCT; OR
    • Later stage; OR
    • High risk factors defined by the presence of any one of the following detected at any time prior to enrollment: deletion of chromosome 13 by conventional cytogenetics, hypodiploidy, abnormality in chromosome 1 (1q amplification or 1p deletion), t(4;14), t(14;16), t(14;20) or deletion of 17p by fluorescence in situ hybridization (FISH) or conventional karyotyping; high risk criteria based on commercially available gene expression profiling; OR
    • Extramedullary disease, plasma cell leukemia or high lactate dehydrogenase (LDH)
  • Patients must have histologically documented myelofibrosis (MF)

    • Patients with Dynamic International Prognostic Scoring System (DIPSS) plus intermediate stage 2 or higher risk MF; OR
    • Subset of intermediate stage 1 patients; defined by:

      • Poor-risk molecular profile (triple negative: JAK2, CALR, MPL); OR
      • Presence of any of the following mutations: ASXL1, SRSF2, EZH2, IDH1/2; OR
      • Severe thrombocytopenia, severe anemia, high peripheral blood blasts percentage; OR
      • Unfavorable cytogenetic abnormalities (rearrangements of chromosome 5 or 7 or >= 3 abnormalities
  • Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines
  • DONOR: A related donor - fully matched
  • DONOR: A related donor - haploidentical
  • DONOR: An unrelated donor - fully matched
  • DONOR: An unrelated donor -9/10 matched

Exclusion Criteria:

  • Cardiac-left ventricular ejection fraction < 40%, symptomatic coronary artery disease, or uncontrolled arrhythmias
  • Pulmonary-forced expiratory volume FEV1 or DLCO < 40% or history of chronic use of supplemental oxygen. Temporary use of supplemental oxygen at the time of screening or registration is allowed if the investigator feels that the underlying cause of requiring oxygen is reversible by the time treatment begins.
  • Renal-calculated or measured glomerular filtration rate (GFR) < 30 ml/min, dialysis-dependent, or history of renal transplant
  • Hepatic-bilirubin > 2 X upper limit of normal (ULN)
  • Alanine aminotransferase (ALT) > 2.5 X ULN or cirrhosis
  • Patients with active or uncontrolled bacterial, viral, or fungal infections requiring systemic therapy
  • Pregnant women, nursing mothers or women of child-bearing potential who are unwilling to use medically accepted methods of contraception
  • Male and female subjects not willing to agree to medically accepted methods of contraception

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03303950


Contacts
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Contact: Kolleen Hicks 801-587-7604 kolleen.hicks@hci.utah.edu

Locations
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United States, Utah
Huntsman Cancer Institute/University of Utah Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Catherine Lee, MD    801-587-0231    Catherine.Lee@hci.utah.edu   
Principal Investigator: Catherine Lee, MD         
Sponsors and Collaborators
University of Utah
Investigators
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Principal Investigator: Catherine Lee, MD Huntsman Cancer Institute/ University of Utah

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Responsible Party: University of Utah
ClinicalTrials.gov Identifier: NCT03303950     History of Changes
Other Study ID Numbers: HCI98381
First Posted: October 6, 2017    Key Record Dates
Last Update Posted: May 14, 2019
Last Verified: May 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Thrombocytopenia
Primary Myelofibrosis
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Blood Platelet Disorders
Myeloproliferative Disorders
Bone Marrow Diseases
Vidarabine
Cyclophosphamide
Busulfan
Fludarabine
Fludarabine phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents