Trial Outcomes & Findings for Nonmyeloablative Haploidentical Transplant Followed by MLN9708 (NCT NCT02169791)

NCT ID: NCT02169791

Last Updated: 2021-09-02

Results Overview

To estimate the incidence of relapse/progression at one-year post-transplant.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 29 participants
• Primary outcome timeframe: 1 year
• Results posted on: 2021-09-02

Participant Flow

This study was opened at our site 7/15/2014 and closed to accrual on 8/28/18. Patients were recruited internally and were considered if they were undergoing a haploidentical transplant for a high risk malignancy.

This was a single arm study with no assignment groups. If patients met criteria they were considered for the study. 29 patients were consented and 25 of those patients were deemed eligible to participate. 4 patients were considered screen failures.

Participant milestones

Measure	Haploidentical Transplant All patients will receive a haploidentical donor transplant using a conditioning regimen of Fludarabine (Flu), cyclophosphamide (cy) and total body irradiation (TBI) followed by MLN9708. MLN9708: MLN9708 will be given weekly x 3 weeks every 28 day cycles, for up to 12 cycles starting at D+5 post-transplant.
Overall Study STARTED	25
Overall Study COMPLETED	18
Overall Study NOT COMPLETED	7

Reasons for withdrawal

Measure	Haploidentical Transplant All patients will receive a haploidentical donor transplant using a conditioning regimen of Fludarabine (Flu), cyclophosphamide (cy) and total body irradiation (TBI) followed by MLN9708. MLN9708: MLN9708 will be given weekly x 3 weeks every 28 day cycles, for up to 12 cycles starting at D+5 post-transplant.
Overall Study Death	6
Overall Study patient withdrew consent	1

Baseline Characteristics

Nonmyeloablative Haploidentical Transplant Followed by MLN9708

Baseline characteristics by cohort

Measure	Haploidentical Transplant n=25 Participants All patients will receive a haploidentical donor transplant using a conditioning regimen of Fludarabine (Flu), cyclophosphamide (cy) and total body irradiation (TBI) followed by MLN9708. MLN9708: MLN9708 will be given weekly x 3 weeks every 28 day cycles, for up to 12 cycles starting at D+5 post-transplant.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	15 Participants n=5 Participants
Age, Categorical >=65 years	10 Participants n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants
Race (NIH/OMB) White	19 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	25 participants n=5 Participants

PRIMARY outcome

Timeframe: 1 year

To estimate the incidence of relapse/progression at one-year post-transplant.

Outcome measures

Measure	Haploidentical Transplant n=25 Participants All patients will receive a haploidentical donor transplant using a conditioning regimen of Fludarabine (Flu), cyclophosphamide (cy) and total body irradiation (TBI) followed by MLN9708. MLN9708: MLN9708 will be given weekly x 3 weeks every 28 day cycles, for up to 12 cycles starting at D+5 post-transplant.
Number of Participants Experiencing Relapse or Progression	10 Participants

SECONDARY outcome

Timeframe: 1 year

Population: All 25 patients were analyzed for time to engraftment

To obtain time to neutrophil engraftment post-transplant

Outcome measures

Measure	Haploidentical Transplant n=25 Participants All patients will receive a haploidentical donor transplant using a conditioning regimen of Fludarabine (Flu), cyclophosphamide (cy) and total body irradiation (TBI) followed by MLN9708. MLN9708: MLN9708 will be given weekly x 3 weeks every 28 day cycles, for up to 12 cycles starting at D+5 post-transplant.
Neutrophil Engraftment	16 days Interval 13.0 to 27.0

SECONDARY outcome

Timeframe: 1 year

To measure the time to platelet recovery post-transplant

Outcome measures

Measure	Haploidentical Transplant n=25 Participants All patients will receive a haploidentical donor transplant using a conditioning regimen of Fludarabine (Flu), cyclophosphamide (cy) and total body irradiation (TBI) followed by MLN9708. MLN9708: MLN9708 will be given weekly x 3 weeks every 28 day cycles, for up to 12 cycles starting at D+5 post-transplant.
Time to Platelet Recovery Post Transplant	29 days Interval 16.0 to 47.0

SECONDARY outcome

Timeframe: 30 days

To measure CD3 donor chimerism post-transplant

Outcome measures

Measure	Haploidentical Transplant n=25 Participants All patients will receive a haploidentical donor transplant using a conditioning regimen of Fludarabine (Flu), cyclophosphamide (cy) and total body irradiation (TBI) followed by MLN9708. MLN9708: MLN9708 will be given weekly x 3 weeks every 28 day cycles, for up to 12 cycles starting at D+5 post-transplant.
Day 30 CD3 Donor Chimerism	100 percentage of chimerism Interval 90.0 to 100.0

SECONDARY outcome

Timeframe: 30 days

To measure CD33 donor chimerism at Day 30

Outcome measures

Measure	Haploidentical Transplant n=25 Participants All patients will receive a haploidentical donor transplant using a conditioning regimen of Fludarabine (Flu), cyclophosphamide (cy) and total body irradiation (TBI) followed by MLN9708. MLN9708: MLN9708 will be given weekly x 3 weeks every 28 day cycles, for up to 12 cycles starting at D+5 post-transplant.
Day 30 CD33 Donor Chimerism	100 percentage of chimerism Interval 93.0 to 100.0

SECONDARY outcome

Timeframe: 100 days

To measure days to onset of acute graft versus host disease

Outcome measures

Measure	Haploidentical Transplant n=25 Participants All patients will receive a haploidentical donor transplant using a conditioning regimen of Fludarabine (Flu), cyclophosphamide (cy) and total body irradiation (TBI) followed by MLN9708. MLN9708: MLN9708 will be given weekly x 3 weeks every 28 day cycles, for up to 12 cycles starting at D+5 post-transplant.
Graft Versus Host Disease	28.5 days Interval 22.0 to 191.0

Adverse Events

Haploidentical Transplant

Serious events: 10 serious events

Other events: 22 other events

Deaths: 8 deaths

Serious adverse events

Measure	Haploidentical Transplant n=25 participants at risk All patients will receive a haploidentical donor transplant using a conditioning regimen of Fludarabine (Flu), cyclophosphamide (cy) and total body irradiation (TBI) followed by MLN9708. MLN9708: MLN9708 will be given weekly x 3 weeks every 28 day cycles, for up to 12 cycles starting at D+5 post-transplant.
Infections and infestations Fever	40.0% 10/25 • Number of events 15 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.
Gastrointestinal disorders Nausea & vomiting	8.0% 2/25 • Number of events 2 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.
Blood and lymphatic system disorders Edema	4.0% 1/25 • Number of events 1 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.
General disorders Hernia	4.0% 1/25 • Number of events 1 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.
General disorders Graft Versus Host Disease	8.0% 2/25 • Number of events 2 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.
Gastrointestinal disorders DIarrhea	4.0% 1/25 • Number of events 1 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.
Infections and infestations Pneumonia	12.0% 3/25 • Number of events 3 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.
Infections and infestations Bacteremia	4.0% 1/25 • Number of events 1 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.
Renal and urinary disorders Dysuria	4.0% 1/25 • Number of events 1 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.
Nervous system disorders Spinal cord compression	4.0% 1/25 • Number of events 1 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.
Blood and lymphatic system disorders Thrombotic microangiopathy	4.0% 1/25 • Number of events 1 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.
Renal and urinary disorders Acute Renal Failure	8.0% 2/25 • Number of events 2 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.
Respiratory, thoracic and mediastinal disorders Acute Respiratory Failure	4.0% 1/25 • Number of events 1 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.
Respiratory, thoracic and mediastinal disorders Hypoxia	4.0% 1/25 • Number of events 1 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.
Vascular disorders Vasculitis	4.0% 1/25 • Number of events 1 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.
Infections and infestations HHV6 infection	4.0% 1/25 • Number of events 1 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.

Other adverse events

Measure	Haploidentical Transplant n=25 participants at risk All patients will receive a haploidentical donor transplant using a conditioning regimen of Fludarabine (Flu), cyclophosphamide (cy) and total body irradiation (TBI) followed by MLN9708. MLN9708: MLN9708 will be given weekly x 3 weeks every 28 day cycles, for up to 12 cycles starting at D+5 post-transplant.
General disorders Graft versus host disease	28.0% 7/25 • Number of events 7 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.
Skin and subcutaneous tissue disorders Skin rash with or without pruritis	32.0% 8/25 • Number of events 8 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.
Cardiac disorders Hypertension	32.0% 8/25 • Number of events 8 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.
Investigations Elevated AST	16.0% 4/25 • Number of events 4 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.
Gastrointestinal disorders Diarrhea	28.0% 7/25 • Number of events 7 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.
Investigations Hyperglycemia	16.0% 4/25 • Number of events 4 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.
Infections and infestations Pneumonia	12.0% 3/25 • Number of events 3 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.
Blood and lymphatic system disorders Neutropenia	20.0% 5/25 • Number of events 5 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.
Cardiac disorders Syncope	8.0% 2/25 • Number of events 2 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.
Metabolism and nutrition disorders Hypokalemia	8.0% 2/25 • Number of events 2 • Adverse Events were collected from the first dose of study drug through 30 days after administration of the last dose of MLN9708. We used the standard definition of adverse events. Only grade 3-4 adverse events were tracked and reported. Grade 3 \& 4 AEs are listed in the 'other non-serious' adverse events as they were documented. They did not meet the definition of serious therefore are listed in the separate category.

Additional Information

Scott R. Solomon, MD

Northside Hospital

Phone: 404-255-1930

Email: ssolomon@bmtga.com

Results disclosure agreements

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