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:

Terminated

Phase:

Phase 2

URL:

https://clinicaltrials.gov/show/NCT03303950

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 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 at one second (FEV1) or diffusion capacity of lung
             for carbon dioxide (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
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Non-relapse Mortality (NRM) at Day 100
Time Frame:Up to day 100
Safety Issue:
Description:NRM is defined as death due to GVHD, infections, sepsis, organ (lung, liver, kidney) toxicity. Death from underlying disease (i.e. progression or relapse) is not considered NRM.

Secondary Outcome Measures

Measure:Non-relapse Mortality (NRM) at Day 365
Time Frame:Up to day 365
Safety Issue:
Description:NRM is defined as death due to GVHD, infections, sepsis, organ (lung, liver, kidney) toxicity. Death from underlying disease (i.e. progression or relapse) is not considered NRM.
Measure:Incidence of Acute Graft Versus Host Disease (GVHD)
Time Frame:Up to day 365
Safety Issue:
Description:Cases of acute graft versus host disease (GVHD) will be diagnosed by the treating physician and will be reported as a count of participants with acute GVHD.
Measure:Incidence of Chronic GVHD
Time Frame:Up to day 365
Safety Issue:
Description:Chronic GVHD will be assessed based on criteria established by the National Institutes of Health Consensus Development Project in 2005, and recently updated in 2014. This will be reported as a count of participants diagnosed with chronic GVHD
Measure:Overall Survival at One Year
Time Frame:Up to 1 year
Safety Issue:
Description:Overall survival is defined as the number of participants remaining alive up to one year following stem cell transplant.
Measure:Disease Free Survival at One Year
Time Frame:Up to 1 year
Safety Issue:
Description:Disease free survival is defined as an absence of disease relapse or progression up to one year following stem cell transplant.
Measure:Number of Clinical Responses
Time Frame:Up to 1 year
Safety Issue:
Description:Response criteria taking into account clinical and molecular markers for Multiple Myeloma (MM) and Myelofibrosis (MF) are specified in the protocol. Available response options are Complete Response (CR), Stringent Complete Response (sCR), Very Good Partial Response (VGPR), Partial Response (PR), or Stable Disease (SD) (also referred to in the protocol as no response).
Measure:Number of Minimal Residual Disease (MRD) Responses
Time Frame:Up to 1 year
Safety Issue:
Description:Bone marrow is collected as specified in the protocol up to one year after bone marrow transplant and evaluated by a clinical pathologist for minimal residual disease (MRD). A response is defined as MRD status negative.

Details

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

Last Updated

March 15, 2021