Allogeneic Stem Cell Transplantation for Multiple Myeloma and Myelofibrosis

NCT03303950 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: HCI98381
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Non-relapse Mortality (NRM) at Day 100

  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.

  Up to day 100

Secondary Outcomes (7)

• Non-relapse Mortality (NRM) at Day 365

  Up to day 365

• Incidence of Acute Graft Versus Host Disease (GVHD)

  Up to day 365

• Incidence of Chronic GVHD

  Up to day 365

• Overall Survival at One Year

  Up to 1 year

• Disease Free Survival at One Year

  Up to 1 year

Study Arms (1)

Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)

EXPERIMENTAL

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.

Drug: Busulfan; Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Hematopoietic Cell Transplantation; Other: Laboratory Biomarker Analysis

Interventions

Busulfan DRUG

Given IV

Also known as: 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

Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-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

Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)

Hematopoietic Cell Transplantation PROCEDURE

Undergo HSCT

Also known as: HCT, Hematopoietic Stem Cell Transplantation, HSCT, stem cell transplantation

Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (busulfan, fludarabine, HSCT, cyclophosphamide)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

Huntsman Cancer Institute/University of Utah

Salt Lake City, Utah, 84112, United States

Location

MeSH Terms

Conditions

Anemia; Multiple Myeloma; Primary Myelofibrosis; Thrombocytopenia

Interventions

Busulfan; Cyclophosphamide; fludarabine; Stem Cell Transplantation; Hematopoietic Stem Cell Transplantation

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Myeloproliferative Disorders; Bone Marrow Diseases; Blood Platelet Disorders; Cytopenia

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Data Manager
• Organization: HCI Research Compliance Office

compliance@hci.utah.edu

8015850601

Study Officials

• Catherine Lee, MD

  Huntsman Cancer Institute/ University of Utah

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2017
• First Posted: October 6, 2017
• Study Start: March 30, 2018
• Primary Completion: May 14, 2019
• Study Completion: February 19, 2020
• Last Updated: May 5, 2022
• Results First Posted: May 27, 2020

Record last verified: 2022-05

Locations

US (1)