Trial Outcomes & Findings for Allogeneic Stem Cell Transplantation for Multiple Myeloma and Myelofibrosis (NCT NCT03303950)

NCT ID: NCT03303950

Last Updated: 2022-05-05

Results Overview

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.

• Recruitment status: TERMINATED
• Study phase: PHASE2
• Target enrollment: 6 participants
• Primary outcome timeframe: Up to day 100
• Results posted on: 2022-05-05

Participant Flow

Participant milestones

Measure	All Particpants - Treatment Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo hematopoietic stem cell transplant (HSCT) on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.
Overall Study STARTED	6
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Allogeneic Stem Cell Transplantation for Multiple Myeloma and Myelofibrosis

Baseline characteristics by cohort

Measure	All Participants - Treatment n=6 Participants Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo hematopoietic stem cell transplant (HSCT) on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	5 Participants n=93 Participants
Age, Categorical >=65 years	1 Participants n=93 Participants
Age, Continuous	54.5 years n=93 Participants
Sex: Female, Male Female	5 Participants n=93 Participants
Sex: Female, Male Male	1 Participants n=93 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=93 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=93 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants
Race (NIH/OMB) White	6 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	All Participants - Treatment n=6 Participants Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo hematopoietic stem cell transplant (HSCT) on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.
Non-relapse Mortality (NRM) at Day 100	1 Participants

SECONDARY outcome

Timeframe: Up to 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.

Outcome measures

Measure	All Participants - Treatment n=6 Participants Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo hematopoietic stem cell transplant (HSCT) on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.
Non-relapse Mortality (NRM) at Day 365	2 Participants

SECONDARY outcome

Timeframe: Up to day 365

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.

Outcome measures

Measure	All Participants - Treatment n=6 Participants Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo hematopoietic stem cell transplant (HSCT) on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.
Incidence of Acute Graft Versus Host Disease (GVHD)	2 Participants

SECONDARY outcome

Timeframe: Up to day 365

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

Outcome measures

Measure	All Participants - Treatment n=6 Participants Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo hematopoietic stem cell transplant (HSCT) on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.
Incidence of Chronic GVHD	1 Participants

SECONDARY outcome

Timeframe: Up to 1 year

Overall survival is defined as the number of participants remaining alive up to one year following stem cell transplant.

Outcome measures

Measure	All Participants - Treatment n=6 Participants Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo hematopoietic stem cell transplant (HSCT) on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.
Overall Survival at One Year	3 Participants

SECONDARY outcome

Timeframe: Up to 1 year

Disease free survival is defined as an absence of disease relapse or progression up to one year following stem cell transplant.

Outcome measures

Measure	All Participants - Treatment n=6 Participants Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo hematopoietic stem cell transplant (HSCT) on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.
Disease Free Survival at One Year	3 Participants

SECONDARY outcome

Timeframe: Up to 1 year

Population: one participant was not evaluable due to failure to engraft (no response assessments performed)

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).

Outcome measures

Measure	All Participants - Treatment n=5 Participants Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo hematopoietic stem cell transplant (HSCT) on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.
Number of Participants With Different Clinical Responses Stringent Complete Response (sCR)	1 Participants
Number of Participants With Different Clinical Responses Very Good Partial Response (VGPR)	1 Participants
Number of Participants With Different Clinical Responses Complete Response (CR)	2 Participants
Number of Participants With Different Clinical Responses Stable Disease (SD)	1 Participants

SECONDARY outcome

Timeframe: Up to 1 year

Population: one participant was not evaluable due to failure to engraft (no response assessments performed)

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.

Outcome measures

Measure	All Participants - Treatment n=5 Participants Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo hematopoietic stem cell transplant (HSCT) on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.
Number of Participants With Minimal Residual Disease (MRD) Response	5 Participants

Adverse Events

All Participants - Treatment

Serious events: 4 serious events

Other events: 5 other events

Deaths: 3 deaths

Serious adverse events

Measure	All Participants - Treatment n=6 participants at risk Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo hematopoietic stem cell transplant (HSCT) on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.
Renal and urinary disorders Acute kidney injury	16.7% 1/6 • Number of events 2 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected from Day -6 (6 days prior to stem cell transplant) to day +365 (365 days after stem cell transplant), approximately one year total. The occurrence of AEs was sought by non-directive questioning of the participant at each visit or phone contact, or when they were volunteered by the participant during or between visits, or through physical examination, laboratory test, or other assessments. Only G3-4 non-hematologic toxicities related to study treatment, engraftment failure, and SAEs were recorded and reported here. Relapse of disease or chronic or acute GVHD were not treated as AEs unless leading to a fatal outcome.
Blood and lymphatic system disorders Blood and lymphatic system disorders - Other	16.7% 1/6 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected from Day -6 (6 days prior to stem cell transplant) to day +365 (365 days after stem cell transplant), approximately one year total. The occurrence of AEs was sought by non-directive questioning of the participant at each visit or phone contact, or when they were volunteered by the participant during or between visits, or through physical examination, laboratory test, or other assessments. Only G3-4 non-hematologic toxicities related to study treatment, engraftment failure, and SAEs were recorded and reported here. Relapse of disease or chronic or acute GVHD were not treated as AEs unless leading to a fatal outcome.
General disorders Death NOS	16.7% 1/6 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected from Day -6 (6 days prior to stem cell transplant) to day +365 (365 days after stem cell transplant), approximately one year total. The occurrence of AEs was sought by non-directive questioning of the participant at each visit or phone contact, or when they were volunteered by the participant during or between visits, or through physical examination, laboratory test, or other assessments. Only G3-4 non-hematologic toxicities related to study treatment, engraftment failure, and SAEs were recorded and reported here. Relapse of disease or chronic or acute GVHD were not treated as AEs unless leading to a fatal outcome.
Gastrointestinal disorders Diarrhea	16.7% 1/6 • Number of events 2 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected from Day -6 (6 days prior to stem cell transplant) to day +365 (365 days after stem cell transplant), approximately one year total. The occurrence of AEs was sought by non-directive questioning of the participant at each visit or phone contact, or when they were volunteered by the participant during or between visits, or through physical examination, laboratory test, or other assessments. Only G3-4 non-hematologic toxicities related to study treatment, engraftment failure, and SAEs were recorded and reported here. Relapse of disease or chronic or acute GVHD were not treated as AEs unless leading to a fatal outcome.
Hepatobiliary disorders Hepatobiliary disorders - Other	16.7% 1/6 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected from Day -6 (6 days prior to stem cell transplant) to day +365 (365 days after stem cell transplant), approximately one year total. The occurrence of AEs was sought by non-directive questioning of the participant at each visit or phone contact, or when they were volunteered by the participant during or between visits, or through physical examination, laboratory test, or other assessments. Only G3-4 non-hematologic toxicities related to study treatment, engraftment failure, and SAEs were recorded and reported here. Relapse of disease or chronic or acute GVHD were not treated as AEs unless leading to a fatal outcome.
Infections and infestations Lung infection	33.3% 2/6 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected from Day -6 (6 days prior to stem cell transplant) to day +365 (365 days after stem cell transplant), approximately one year total. The occurrence of AEs was sought by non-directive questioning of the participant at each visit or phone contact, or when they were volunteered by the participant during or between visits, or through physical examination, laboratory test, or other assessments. Only G3-4 non-hematologic toxicities related to study treatment, engraftment failure, and SAEs were recorded and reported here. Relapse of disease or chronic or acute GVHD were not treated as AEs unless leading to a fatal outcome.
Respiratory, thoracic and mediastinal disorders Respiratory failure	16.7% 1/6 • Number of events 3 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected from Day -6 (6 days prior to stem cell transplant) to day +365 (365 days after stem cell transplant), approximately one year total. The occurrence of AEs was sought by non-directive questioning of the participant at each visit or phone contact, or when they were volunteered by the participant during or between visits, or through physical examination, laboratory test, or other assessments. Only G3-4 non-hematologic toxicities related to study treatment, engraftment failure, and SAEs were recorded and reported here. Relapse of disease or chronic or acute GVHD were not treated as AEs unless leading to a fatal outcome.
Infections and infestations Sepsis	16.7% 1/6 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected from Day -6 (6 days prior to stem cell transplant) to day +365 (365 days after stem cell transplant), approximately one year total. The occurrence of AEs was sought by non-directive questioning of the participant at each visit or phone contact, or when they were volunteered by the participant during or between visits, or through physical examination, laboratory test, or other assessments. Only G3-4 non-hematologic toxicities related to study treatment, engraftment failure, and SAEs were recorded and reported here. Relapse of disease or chronic or acute GVHD were not treated as AEs unless leading to a fatal outcome.
Respiratory, thoracic and mediastinal disorders Sinus disorder	16.7% 1/6 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected from Day -6 (6 days prior to stem cell transplant) to day +365 (365 days after stem cell transplant), approximately one year total. The occurrence of AEs was sought by non-directive questioning of the participant at each visit or phone contact, or when they were volunteered by the participant during or between visits, or through physical examination, laboratory test, or other assessments. Only G3-4 non-hematologic toxicities related to study treatment, engraftment failure, and SAEs were recorded and reported here. Relapse of disease or chronic or acute GVHD were not treated as AEs unless leading to a fatal outcome.

Other adverse events

Measure	All Participants - Treatment n=6 participants at risk Participants receive busulfan IV over 2 hours and fludarabine IV over 30 minutes on days -5 to -2. Participants undergo hematopoietic stem cell transplant (HSCT) on day 0. Participants then receive cyclophosphamide IV over 60 minutes on days 3 and 4.
Blood and lymphatic system disorders Anemia	16.7% 1/6 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected from Day -6 (6 days prior to stem cell transplant) to day +365 (365 days after stem cell transplant), approximately one year total. The occurrence of AEs was sought by non-directive questioning of the participant at each visit or phone contact, or when they were volunteered by the participant during or between visits, or through physical examination, laboratory test, or other assessments. Only G3-4 non-hematologic toxicities related to study treatment, engraftment failure, and SAEs were recorded and reported here. Relapse of disease or chronic or acute GVHD were not treated as AEs unless leading to a fatal outcome.
Investigations Blood bilirubin increased	16.7% 1/6 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected from Day -6 (6 days prior to stem cell transplant) to day +365 (365 days after stem cell transplant), approximately one year total. The occurrence of AEs was sought by non-directive questioning of the participant at each visit or phone contact, or when they were volunteered by the participant during or between visits, or through physical examination, laboratory test, or other assessments. Only G3-4 non-hematologic toxicities related to study treatment, engraftment failure, and SAEs were recorded and reported here. Relapse of disease or chronic or acute GVHD were not treated as AEs unless leading to a fatal outcome.
Investigations Creatinine increased	16.7% 1/6 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected from Day -6 (6 days prior to stem cell transplant) to day +365 (365 days after stem cell transplant), approximately one year total. The occurrence of AEs was sought by non-directive questioning of the participant at each visit or phone contact, or when they were volunteered by the participant during or between visits, or through physical examination, laboratory test, or other assessments. Only G3-4 non-hematologic toxicities related to study treatment, engraftment failure, and SAEs were recorded and reported here. Relapse of disease or chronic or acute GVHD were not treated as AEs unless leading to a fatal outcome.
Metabolism and nutrition disorders Hypokalemia	33.3% 2/6 • Number of events 4 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected from Day -6 (6 days prior to stem cell transplant) to day +365 (365 days after stem cell transplant), approximately one year total. The occurrence of AEs was sought by non-directive questioning of the participant at each visit or phone contact, or when they were volunteered by the participant during or between visits, or through physical examination, laboratory test, or other assessments. Only G3-4 non-hematologic toxicities related to study treatment, engraftment failure, and SAEs were recorded and reported here. Relapse of disease or chronic or acute GVHD were not treated as AEs unless leading to a fatal outcome.
Metabolism and nutrition disorders Hypophosphatemia	16.7% 1/6 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected from Day -6 (6 days prior to stem cell transplant) to day +365 (365 days after stem cell transplant), approximately one year total. The occurrence of AEs was sought by non-directive questioning of the participant at each visit or phone contact, or when they were volunteered by the participant during or between visits, or through physical examination, laboratory test, or other assessments. Only G3-4 non-hematologic toxicities related to study treatment, engraftment failure, and SAEs were recorded and reported here. Relapse of disease or chronic or acute GVHD were not treated as AEs unless leading to a fatal outcome.
Respiratory, thoracic and mediastinal disorders Hypoxia	16.7% 1/6 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected from Day -6 (6 days prior to stem cell transplant) to day +365 (365 days after stem cell transplant), approximately one year total. The occurrence of AEs was sought by non-directive questioning of the participant at each visit or phone contact, or when they were volunteered by the participant during or between visits, or through physical examination, laboratory test, or other assessments. Only G3-4 non-hematologic toxicities related to study treatment, engraftment failure, and SAEs were recorded and reported here. Relapse of disease or chronic or acute GVHD were not treated as AEs unless leading to a fatal outcome.
Psychiatric disorders Insomnia	16.7% 1/6 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected from Day -6 (6 days prior to stem cell transplant) to day +365 (365 days after stem cell transplant), approximately one year total. The occurrence of AEs was sought by non-directive questioning of the participant at each visit or phone contact, or when they were volunteered by the participant during or between visits, or through physical examination, laboratory test, or other assessments. Only G3-4 non-hematologic toxicities related to study treatment, engraftment failure, and SAEs were recorded and reported here. Relapse of disease or chronic or acute GVHD were not treated as AEs unless leading to a fatal outcome.
Metabolism and nutrition disorders Hypomagnesemia	16.7% 1/6 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected from Day -6 (6 days prior to stem cell transplant) to day +365 (365 days after stem cell transplant), approximately one year total. The occurrence of AEs was sought by non-directive questioning of the participant at each visit or phone contact, or when they were volunteered by the participant during or between visits, or through physical examination, laboratory test, or other assessments. Only G3-4 non-hematologic toxicities related to study treatment, engraftment failure, and SAEs were recorded and reported here. Relapse of disease or chronic or acute GVHD were not treated as AEs unless leading to a fatal outcome.
Nervous system disorders Syncope	16.7% 1/6 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected from Day -6 (6 days prior to stem cell transplant) to day +365 (365 days after stem cell transplant), approximately one year total. The occurrence of AEs was sought by non-directive questioning of the participant at each visit or phone contact, or when they were volunteered by the participant during or between visits, or through physical examination, laboratory test, or other assessments. Only G3-4 non-hematologic toxicities related to study treatment, engraftment failure, and SAEs were recorded and reported here. Relapse of disease or chronic or acute GVHD were not treated as AEs unless leading to a fatal outcome.
Infections and infestations Urinary tract infection	16.7% 1/6 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected from Day -6 (6 days prior to stem cell transplant) to day +365 (365 days after stem cell transplant), approximately one year total. The occurrence of AEs was sought by non-directive questioning of the participant at each visit or phone contact, or when they were volunteered by the participant during or between visits, or through physical examination, laboratory test, or other assessments. Only G3-4 non-hematologic toxicities related to study treatment, engraftment failure, and SAEs were recorded and reported here. Relapse of disease or chronic or acute GVHD were not treated as AEs unless leading to a fatal outcome.
Nervous system disorders Vasovagal reaction	16.7% 1/6 • Adverse Events (AEs) and Serious Adverse Events (SAEs) were collected from Day -6 (6 days prior to stem cell transplant) to day +365 (365 days after stem cell transplant), approximately one year total. The occurrence of AEs was sought by non-directive questioning of the participant at each visit or phone contact, or when they were volunteered by the participant during or between visits, or through physical examination, laboratory test, or other assessments. Only G3-4 non-hematologic toxicities related to study treatment, engraftment failure, and SAEs were recorded and reported here. Relapse of disease or chronic or acute GVHD were not treated as AEs unless leading to a fatal outcome.

Additional Information

Data Manager

HCI Research Compliance Office

Phone: 8015850601

Email: compliance@hci.utah.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place