Allogeneic Stem Cell Transplantation for Multiple Myeloma and Myelofibrosis

NCT ID: NCT03303950

Last Updated: 2022-05-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-03-30
• Study Completion Date: 2020-02-19

Brief Summary

This phase II trial studies how well busulfan, fludarabine, donor stem cell transplant, and cyclophosphamide in treating participants 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 participant they may help the participant'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 participants 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:

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

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

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)

Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo HSCT on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.

Group Type: EXPERIMENTAL

Busulfan

Intervention Type: DRUG

Given IV

Cyclophosphamide

Intervention Type: DRUG

Given IV

Fludarabine

Intervention Type: DRUG

Given IV

Hematopoietic Cell Transplantation

Intervention Type: PROCEDURE

Undergo HSCT

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Interventions

Busulfan

Given IV

Intervention Type: DRUG

Cyclophosphamide

Given IV

Intervention Type: DRUG

Fludarabine

Given IV

Intervention Type: DRUG

Hematopoietic Cell Transplantation

Undergo HSCT

Intervention Type: PROCEDURE

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Other Intervention 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; (-)-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; Fluradosa; HCT; Hematopoietic Stem Cell Transplantation; HSCT; stem cell transplantation

Eligibility Criteria

Inclusion Criteria

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

• Participants 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)
• Participants must have histologically documented myelofibrosis (MF)

• Participants with Dynamic International Prognostic Scoring System (DIPSS) plus intermediate stage 2 or higher risk MF; OR
• Subset of intermediate stage 1 participants; 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
• Participants 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Utah

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Catherine Lee, MD

Role: PRINCIPAL_INVESTIGATOR

Huntsman Cancer Institute/ University of Utah

Locations

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

HCI98381

Identifier Type: -

Identifier Source: org_study_id