Clinical Trials /

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

NCT03303950

Description:

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.

Related Conditions:
  • Multiple Myeloma
  • Myelofibrosis
  • Plasma Cell Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Busulfan, Fludarabine, Donor Stem Cell Transplant, and Cyclophosphamide in Treating Patients With Multiple Myeloma or Myelofibrosis
  • Official Title: Allogeneic Stem Cell Transplantation for Multiple Myeloma and Myelofibrosis

Clinical Trial IDs

  • ORG STUDY ID: HCI98381
  • NCT ID: NCT03303950

Conditions

  • 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

Interventions

DrugSynonymsArms
Busulfan1, 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-19508Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)
Cyclophosphamide(-)-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- 138719Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)
FludarabineFluradosaTreatment (busulfan, fludarabine, HSCT, cyclophosphamide)

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)ExperimentalPatients 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.
  • Busulfan
  • Cyclophosphamide
  • Fludarabine

Eligibility 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 sibling donor - fully matched

          -  DONOR: A sibling 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 in 1 second (FEV1) or carbon monoxide diffusing
             capability (DLco) < 40% or need for use of supplemental oxygen

          -  Renal-calculated or measured glomerular filtration rate (GFR) < 40 ml/min, dialysis
             requirement, or prior 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
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Non-relapse mortality (NRM)
Time Frame:Up to day 100
Safety Issue:
Description: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

Measure:Cumulative incidence of clinical complete response and molecular complete response (complete response and partial response)
Time Frame:Up to 1 year
Safety Issue:
Description:
Measure:Disease free survival
Time Frame:Up to 1 year
Safety Issue:
Description:Kaplan-Meier techniques will be used.
Measure:Incidence of acute graft versus host disease (GVHD)
Time Frame:Up to day 365
Safety Issue:
Description:Will be done descriptively.
Measure:Incidence of chronic GVHD
Time Frame:Up to day 365
Safety Issue:
Description: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.
Measure:Non-relapse mortality
Time Frame:Up to day 365
Safety Issue:
Description:Will be done descriptively.
Measure:Overall survival
Time Frame:Up to 1 year
Safety Issue:
Description:Kaplan-Meier techniques will be used.
Measure:Relapse rate
Time Frame:Up to day 365
Safety Issue:
Description:Will be done descriptively.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Utah

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