Trial Outcomes & Findings for Reduced-Intensity Busulfan and Fludarabine With or Without Antithymocyte Globulin Followed by Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Other Disease (NCT NCT00448201)

NCT ID: NCT00448201

Last Updated: 2017-05-30

Results Overview

Treatment related mortality for first 6 months. Defined as the number of treatment related deaths excluding deaths due to disease relapse.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 71 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2017-05-30

Participant Flow

Patients with histologically confirmed hematologic malignancies, who were over the age of 55, or otherwise ineligible for more intensive busulfan-based therapy were enrolled on protocol Lineberger Comprehensive Cancer Center (LCCC) 0306 at the University of North Carolina.

Participant milestones

Measure	All Trial Participants All patients received IV fludarabine 30 mg/m2/day on days -7 through -3; busulfan 6.4 mg/kg by continuous infusion over 48 hours on days -6 through -5 and tacrolimus from day -1. Throughout the study duration, 8 different GVHD regimens were investigated. In addition to tacrolimus, patients received combinations of 3 agents: methotrexate (5 mg/m2 D1, 3, 6), rabbit antithymocyte globulin (ATG, 3 mg/kg to- 6 mg/kg) or alemtuzumab (Campath, 30 mg to- 90 mg).
Overall Study STARTED	71
Overall Study COMPLETED	71
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Reduced-Intensity Busulfan and Fludarabine With or Without Antithymocyte Globulin Followed by Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer or Other Disease

Baseline characteristics by cohort

Measure	All Trial Participants n=71 Participants All patients received IV fludarabine 30 mg/m2/day on days -7 through -3; busulfan 6.4 mg/kg by continuous infusion over 48 hours on days -6 through -5 and tacrolimus from day -1. Throughout the study duration, 8 different GVHD regimens were investigated. In addition to tacrolimus, patients received combinations of 3 agents: methotrexate (5 mg/m2 D1, 3, 6), rabbit antithymocyte globulin (ATG, 3 mg/kg to- 6 mg/kg) or alemtuzumab (Campath, 30 mg to- 90 mg).
Age, Continuous	58 years n=5 Participants
Sex: Female, Male Female	31 Participants n=5 Participants
Sex: Female, Male Male	40 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 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	9 Participants n=5 Participants
Race (NIH/OMB) White	60 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment United States	71 participants n=5 Participants
Donor Types HLA-matched related donor (MRD)	37 Participants n=5 Participants
Donor Types MUD or HLA-mismatched grafts	34 Participants n=5 Participants
Comorbidity Index (CI)	3 units on a scale n=5 Participants
Disease Risk Index (DRI) Low	9 Participants n=5 Participants
Disease Risk Index (DRI) Intermediate	40 Participants n=5 Participants
Disease Risk Index (DRI) High	19 Participants n=5 Participants
Disease Risk Index (DRI) Very High	1 Participants n=5 Participants
Disease Risk Index (DRI) Undetermined	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Treatment related mortality for first 6 months. Defined as the number of treatment related deaths excluding deaths due to disease relapse.

Outcome measures

Measure	All Trial Participants n=71 Participants All patients received IV fludarabine 30 mg/m2/day on days -7 through -3; busulfan 6.4 mg/kg by continuous infusion over 48 hours on days -6 through -5 and tacrolimus from day -1. Throughout the study duration, 8 different GVHD regimens were investigated. In addition to tacrolimus, patients received combinations of 3 agents: methotrexate (5 mg/m2 D1, 3, 6), rabbit antithymocyte globulin (ATG, 3 mg/kg to- 6 mg/kg) or alemtuzumab (Campath, 30 mg to- 90 mg).	Day 90 90 days post-transplant
Treatment-related Mortality	8.4 percentage of participants	—

SECONDARY outcome

Timeframe: 6 and 12 months

Population: Complete response was not calculated at 6 and 12 months because the majority of patients had complete response at the time of transplant.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Days 30, 60, and 90

Complete chimerism is defined as 100% donor cells detected, suggesting complete hematopoietic replacement. Mixed donor chimerism means host cells are detected in particular cells like lymphocytes. Five to 90% donor cells set the criteria for mixed chimerism (MC).

Chimerism was not tabulated on day 30.

Outcome measures

Measure	All Trial Participants n=71 Participants All patients received IV fludarabine 30 mg/m2/day on days -7 through -3; busulfan 6.4 mg/kg by continuous infusion over 48 hours on days -6 through -5 and tacrolimus from day -1. Throughout the study duration, 8 different GVHD regimens were investigated. In addition to tacrolimus, patients received combinations of 3 agents: methotrexate (5 mg/m2 D1, 3, 6), rabbit antithymocyte globulin (ATG, 3 mg/kg to- 6 mg/kg) or alemtuzumab (Campath, 30 mg to- 90 mg).	Day 90 n=71 Participants 90 days post-transplant
Complete or Mixed Donor Chimerism at 30, 60, and 90 Days Post-transplant Complete Donor	82 percentage of patients	87 percentage of patients
Complete or Mixed Donor Chimerism at 30, 60, and 90 Days Post-transplant Mixed Donor	18 percentage of patients	13 percentage of patients

SECONDARY outcome

Timeframe: Year 5

The length of time post-transplant that the patient survives without any signs or symptoms of that cancer.

Outcome measures

Measure	All Trial Participants n=71 Participants All patients received IV fludarabine 30 mg/m2/day on days -7 through -3; busulfan 6.4 mg/kg by continuous infusion over 48 hours on days -6 through -5 and tacrolimus from day -1. Throughout the study duration, 8 different GVHD regimens were investigated. In addition to tacrolimus, patients received combinations of 3 agents: methotrexate (5 mg/m2 D1, 3, 6), rabbit antithymocyte globulin (ATG, 3 mg/kg to- 6 mg/kg) or alemtuzumab (Campath, 30 mg to- 90 mg).	Day 90 90 days post-transplant
5-year Disease-free Survival	31 percentage of participants	—

SECONDARY outcome

Timeframe: 6 Months

Graft-vs-host disease (GVHD) can be mild, moderate or severe depending on the differences in tissue type between patient and donor. Its symptoms can include:

• Rashes, which include burning and redness, that erupt on the palms or soles and may spread to the trunk and eventually to the entire body
• Blistering, causing the exposed skin surface to flake off in severe cases
• Nausea, vomiting, abdominal cramps, diarrhea and loss of appetite, which can indicate that the gastrointestinal (digestive) tract is affected
• Jaundice, or a yellowing of the skin, which can indicate liver damage
• Excessive dryness of the mouth and throat, leading to ulcers
• Dryness of the lungs, vagina and other surfaces

Acute GVHD - Can occur soon after the transplanted cells begin to appear in the recipient. Acute GVHD ranges from mild, moderate or severe, and can be life-threatening if its effects are not controlled.

Extensive chronic GVHD - Usually occurs at about three months post-transplant.

Outcome measures

Measure	All Trial Participants n=71 Participants All patients received IV fludarabine 30 mg/m2/day on days -7 through -3; busulfan 6.4 mg/kg by continuous infusion over 48 hours on days -6 through -5 and tacrolimus from day -1. Throughout the study duration, 8 different GVHD regimens were investigated. In addition to tacrolimus, patients received combinations of 3 agents: methotrexate (5 mg/m2 D1, 3, 6), rabbit antithymocyte globulin (ATG, 3 mg/kg to- 6 mg/kg) or alemtuzumab (Campath, 30 mg to- 90 mg).	Day 90 90 days post-transplant
Graft-vs-host Disease at 6 Months Post-transplant Acute GVHD	13 percentage of participants	—
Graft-vs-host Disease at 6 Months Post-transplant Extensive Chronic GVHD	30 percentage of participants	—

Adverse Events

All Trial Participants

Serious events: 7 serious events

Other events: 0 other events

Deaths: 44 deaths

Serious adverse events

Measure	All Trial Participants n=71 participants at risk All patients received IV fludarabine 30 mg/m2/day on days -7 through -3; busulfan 6.4 mg/kg by continuous infusion over 48 hours on days -6 through -5 and tacrolimus from day -1. Throughout the study duration, 8 different GVHD regimens were investigated. In addition to tacrolimus, patients received combinations of 3 agents: methotrexate (5 mg/m2 D1, 3, 6), rabbit antithymocyte globulin (ATG, 3 mg/kg to- 6 mg/kg) or alemtuzumab (Campath, 30 mg to- 90 mg).
Blood and lymphatic system disorders hypoxemia	1.4% 1/71 • 1 year
Blood and lymphatic system disorders graft failure	1.4% 1/71 • 1 year
Hepatobiliary disorders liver toxicity/hyperbilirubinemia	1.4% 1/71 • 1 year
Gastrointestinal disorders Graft vs host disease grade 4	4.2% 3/71 • 1 year
Infections and infestations CMV viremia	1.4% 1/71 • 1 year
Vascular disorders subdural hematoma	1.4% 1/71 • 1 year
Infections and infestations Fever	2.8% 2/71 • 1 year
General disorders Failure to thrive	1.4% 1/71 • 1 year
Gastrointestinal disorders elevated lipase	1.4% 1/71 • 1 year
Infections and infestations CMV pneumonia	1.4% 1/71 • 1 year
Infections and infestations BK viruria	1.4% 1/71 • 1 year
Infections and infestations fungal pneumonia	1.4% 1/71 • 1 year
Infections and infestations bronchiolitis obliterans organizing pneumonia	1.4% 1/71 • 1 year
Infections and infestations EBV viremia	1.4% 1/71 • 1 year
Infections and infestations nocardia pneumonia	1.4% 1/71 • 1 year
General disorders toxic epidermal nectrolysis	1.4% 1/71 • 1 year

Other adverse events

Adverse event data not reported

Additional Information

Dr. Thomas Shea

UNC Lineberger Comprehensive Cancer Center

Phone: 919-966-7746

Email: tom_shea@med.unc.edu

Results disclosure agreements

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