AnemiaPhase 2NCT03303950
Allogeneic Stem Cell Transplantation for Multiple Myeloma and Myelofibrosis
A Phase 2 study testing Busulfan, Cyclophosphamide and Fludarabine in people with Anemia and ASXL1 Gene Mutation, run by University of Utah at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Anemia, ASXL1 Gene Mutation, EZH2 Gene Mutation
- What is being tested?
- Busulfan, Cyclophosphamide and Fludarabine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 30 Mar 2018to 19 Feb 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Huntsman Cancer Institute/University of Utah
Salt Lake City, Utah, 84112
About this study
Official title: Busulfan, Fludarabine, Donor Stem Cell Transplant, and Cyclophosphamide in Treating Participants With Multiple Myeloma or Myelofibrosis
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.
Read the detailed description
PRIMARY OBJECTIVES:
- To evaluate non-relapse mortality (NRM) up to day +100.
SECONDARY OBJECTIVES:
- 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
- Being tested
- Busulfan, Cyclophosphamide, Fludarabine, Hematopoietic Cell Transplantation, Laboratory Biomarker Analysis
- Medical subject headings
- Anemia, Multiple Myeloma, Primary Myelofibrosis, Thrombocytopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BusulfanDrug
Also called 1, 4-Bis[methanesulfonoxy]butane, BUS, Bussulfam, Busulfanum
Given IV
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida
Given IV
FludarabineDrug
Also called Fluradosa
Given IV
Hematopoietic Cell TransplantationProcedure or surgery
Also called HCT, Hematopoietic Stem Cell Transplantation, HSCT, stem cell transplantation
Undergo HSCT
Laboratory Biomarker AnalysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Busulfan; Drug: Cyclophosphamide; Drug: Fludarabine; Procedure: Hematopoietic Cell Transplantation; Other: Laboratory Biomarker Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to day 100
Secondary outcomes (7)
Non-relapse Mortality (NRM) at Day 365
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.
Measured: Up to day 365
Incidence of Acute Graft Versus Host Disease (GVHD)
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.
Measured: Up to day 365
Incidence of Chronic GVHD
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
Measured: Up to day 365
Overall Survival at One Year
Overall survival is defined as the number of participants remaining alive up to one year following stem cell transplant.
Measured: Up to 1 year
Disease Free Survival at One Year
Disease free survival is defined as an absence of disease relapse or progression up to one year following stem cell transplant.
Measured: Up to 1 year
Number of Participants With Different Clinical Responses
Clinical Responses were determined by disease-specific criteria taking into account multiple clinical and molecular markers. Multiple Myeloma (MM) response was determined using International Myeloma Working Group (IMWG) consensus criteria for response. Participants with MM had either Stringent Complete Response (sCR) or Very Good Partial Response (VGPR). Myelofibrosis (MF) response was determined using International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus criteria. Participants with MF had either Complete Response (CR) or Stable Disease (SD) (also referred to in the protocol as no response).
Measured: Up to 1 year
Number of Participants With Minimal Residual Disease (MRD) Response
After bone marrow transplant, bone marrow was collected every 3-6 months (as clinically indicated per treating investigator) for up to one year after bone marrow transplant. Bone marrow was evaluated by a clinical pathologist for any evidence of multiple myeloma (MM) or myelofibrosis (MF). Evidence of MM or MF in the bone marrow is referred to as minimal residual disease (MRD). A participant with evidence of MRD is MRD-positive. A participant with no evidence of MRD is MRD-negative, which is considered an MRD response. This outcome reports the number participants with MRD responses any time between bone marrow transplant up to one year of follow-up.
Measured: Up to 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2017
- Study start30 Mar 2018
- Primary completion14 May 2019
- Study completion19 Feb 2020
Why it stopped: Slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for AnemiaStudies of the same condition, open and under way.
- More trials run by University of UtahThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Catherine Lee, MD, Principal investigator, Huntsman Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03303950
- Sponsor's protocol ID
- HCI98381
- Status last verified
- May 2022
- First submitted
- 2 Oct 2017
- Last updated
- 5 May 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Busulfan, Fludarabine, Donor Stem Cell Transplant, and Cyclophosphamide in Treating Participants With Multiple Myeloma or Myelofibrosis
- ClinicalTrials.gov ID
- NCT03303950
- Acronym / sponsor ID
- HCI98381
- Conditions
- Anemia, ASXL1 Gene Mutation, EZH2 Gene Mutation, IDH1 Gene Mutation, IDH2 Gene Mutation, Plasma Cell Myeloma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual
- Enrolment
- 6 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Study start
- 30 Mar 2018 (actual)
- Primary completion
- 14 May 2019 (actual)
- Study completion
- 19 Feb 2020 (actual)
- First posted
- 6 Oct 2017 (actual)
- Results
- Posted 27 May 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- To evaluate non-relapse mortality (NRM) up to day +100.
SECONDARY OBJECTIVES:
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (busulfan, fludarabine, HSCT, cyclophosphamide) | Experimental | Drug: Busulfan, Drug: Cyclophosphamide, Drug: Fludarabine, Procedure: Hematopoietic Cell Transplantation, Other: Laboratory Biomarker AnalysisParticipants 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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 must have histologically documented myelofibrosis (MF)
- Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BusulfanAlso: 1, 4-Bis[methanesulfonoxy]butane, BUS, Bussulfam, BusulfanumGiven IV | Drug | Treatment (busulfan, fludarabine, HSCT, cyclophosphamide) |
| CyclophosphamideAlso: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, CiclofosfamidaGiven IV | Drug | Treatment (busulfan, fludarabine, HSCT, cyclophosphamide) |
| FludarabineAlso: FluradosaGiven IV | Drug | Treatment (busulfan, fludarabine, HSCT, cyclophosphamide) |
| Hematopoietic Cell TransplantationAlso: HCT, Hematopoietic Stem Cell Transplantation, HSCT, stem cell transplantationUndergo HSCT | Procedure or surgery | Treatment (busulfan, fludarabine, HSCT, cyclophosphamide) |
| Laboratory Biomarker AnalysisCorrelative studies | Other | Treatment (busulfan, fludarabine, HSCT, cyclophosphamide) |
Primary outcome
Non-relapse Mortality (NRM) at Day 100
Time frame: Up to 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.
7 secondary outcomes
Non-relapse Mortality (NRM) at Day 365
Time frame: Up to day 365
Incidence of Acute Graft Versus Host Disease (GVHD)
Time frame: Up to day 365
Incidence of Chronic GVHD
Time frame: Up to day 365
Overall Survival at One Year
Time frame: Up to 1 year
Disease Free Survival at One Year
Time frame: Up to 1 year
Number of Participants With Different Clinical Responses
Time frame: Up to 1 year
Number of Participants With Minimal Residual Disease (MRD) Response
Time frame: Up to 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Catherine Lee, MD principal investigator
Huntsman Cancer Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Busulfan, Cyclophosphamide and Fludarabine in people with Anemia and ASXL1 Gene Mutation, run by University of Utah at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 May 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Non-relapse Mortality (NRM) at Day 100 (time frame: Up to day 100). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 May 2022.