Trial Outcomes & Findings for Alloreactive Haploidentical Natural Killer (NK) Cells With Busulfan and Fludarabine/ATG (NCT NCT01390402)

Results Overview

Molecular Complete Remission is defined as participant alive and engrafted with molecular complete remission 100 days post transplant where molecular complete response is no BCR-ABL transcripts detected and engraftment is defined as the evidence of donor derived cells (more than 95%) by chimerism studies in the presence of neutrophil recovery by day 28 post stem cell infusion.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

6 participants

Primary outcome timeframe

Baseline to up to 4 months post-transplant

Results posted on

2016-02-03

Participant Flow

Recruitment Period: January 24, 2012 to August 1, 2013. All recruitment done at The University of Texas (UT) MD Anderson Cancer Center.

Participant milestones

Participant milestones
Measure	NK Infusion + Chemotherapy Fludarabine 40 mg/m\^2 intravenous (IV) daily for four (4) consecutive days, Days -13 to -10, immediately followed by Busulfan 130 mg/ m\^2 IV for 2 doses on Days -11 to -10 and Natural killer (NK) cell infusion Iv administered on Day -8. Interleukin-2: 0.5 million units subcutaneously daily for 5 days on Day -8 to day -4; Anti-Thymocyte Globulin: 2.5 mg/kg IV for 3 doses on Days -3 to -1. Allogeneic related stem cell transplant IV Day 0. Tacrolimus: Starting dose of 0.015 mg/kg (ideal body weight) as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml. Methotrexate 5 mg/m2 by vein Days 1, 3 and 6 post transplant. G-CSF 5 mcg/kg/day subcutaneously beginning on Day + 7.
Overall Study STARTED	6
Overall Study COMPLETED	1
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Reasons for withdrawal
Measure	NK Infusion + Chemotherapy Fludarabine 40 mg/m\^2 intravenous (IV) daily for four (4) consecutive days, Days -13 to -10, immediately followed by Busulfan 130 mg/ m\^2 IV for 2 doses on Days -11 to -10 and Natural killer (NK) cell infusion Iv administered on Day -8. Interleukin-2: 0.5 million units subcutaneously daily for 5 days on Day -8 to day -4; Anti-Thymocyte Globulin: 2.5 mg/kg IV for 3 doses on Days -3 to -1. Allogeneic related stem cell transplant IV Day 0. Tacrolimus: Starting dose of 0.015 mg/kg (ideal body weight) as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml. Methotrexate 5 mg/m2 by vein Days 1, 3 and 6 post transplant. G-CSF 5 mcg/kg/day subcutaneously beginning on Day + 7.
Overall Study Death	1
Overall Study Disease Progression	4

Baseline Characteristics

Alloreactive Haploidentical Natural Killer (NK) Cells With Busulfan and Fludarabine/ATG

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	NK Infusion + Chemotherapy n=6 Participants Fludarabine 40 mg/m\^2 intravenous (IV) daily for four (4) consecutive days, Days -13 to -10, immediately followed by Busulfan 130 mg/ m\^2 IV for 2 doses on Days -11 to -10 and Natural killer (NK) cell infusion Iv administered on Day -8. Interleukin-2: 0.5 million units subcutaneously daily for 5 days on Day -8 to day -4; Anti-Thymocyte Globulin: 2.5 mg/kg IV for 3 doses on Days -3 to -1. Allogeneic related stem cell transplant IV Day 0. Tacrolimus: Starting dose of 0.015 mg/kg (ideal body weight) as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml. Methotrexate 5 mg/m2 by vein Days 1, 3 and 6 post transplant. G-CSF 5 mcg/kg/day subcutaneously beginning on Day + 7.
Age, Continuous	46 years n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to up to 4 months post-transplant

Molecular Complete Remission is defined as participant alive and engrafted with molecular complete remission 100 days post transplant where molecular complete response is no BCR-ABL transcripts detected and engraftment is defined as the evidence of donor derived cells (more than 95%) by chimerism studies in the presence of neutrophil recovery by day 28 post stem cell infusion.

Outcome measures

Outcome measures
Measure	NK Infusion + Chemotherapy n=6 Participants Fludarabine 40 mg/m\^2 intravenous (IV) daily for four (4) consecutive days, Days -13 to -10, immediately followed by Busulfan 130 mg/ m\^2 IV for 2 doses on Days -11 to -10 and Natural killer (NK) cell infusion Iv administered on Day -8. Interleukin-2: 0.5 million units subcutaneously daily for 5 days on Day -8 to day -4; Anti-Thymocyte Globulin: 2.5 mg/kg IV for 3 doses on Days -3 to -1. Allogeneic related stem cell transplant IV Day 0. Tacrolimus: Starting dose of 0.015 mg/kg (ideal body weight) as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml. Methotrexate 5 mg/m2 by vein Days 1, 3 and 6 post transplant. G-CSF 5 mcg/kg/day subcutaneously beginning on Day + 7.
Number of Participants With Molecular Complete Remission at 3 Month Post Transplant	3 participants

Adverse Events

NK Infusion + Chemotherapy

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	NK Infusion + Chemotherapy n=6 participants at risk Fludarabine 40 mg/m\^2 intravenous (IV) daily for four (4) consecutive days, Days -13 to -10, immediately followed by Busulfan 130 mg/ m\^2 IV for 2 doses on Days -11 to -10 and Natural killer (NK) cell infusion Iv administered on Day -8. Interleukin-2: 0.5 million units subcutaneously daily for 5 days on Day -8 to day -4; Anti-Thymocyte Globulin: 2.5 mg/kg IV for 3 doses on Days -3 to -1. Allogeneic related stem cell transplant IV Day 0. Tacrolimus: Starting dose of 0.015 mg/kg (ideal body weight) as a 24 hour continuous infusion daily adjusted to achieve a therapeutic level of 5-15 ng/ml. Methotrexate 5 mg/m2 by vein Days 1, 3 and 6 post transplant. G-CSF 5 mcg/kg/day subcutaneously beginning on Day + 7.
Gastrointestinal disorders Ascites	16.7% 1/6 • Number of events 1 • Adverse event collection from the start of preparative regimen up to Day+100.
Immune system disorders Allergic reaction	16.7% 1/6 • Number of events 1 • Adverse event collection from the start of preparative regimen up to Day+100.
Gastrointestinal disorders GI Graft versus Host Disease (GVHD)	33.3% 2/6 • Number of events 2 • Adverse event collection from the start of preparative regimen up to Day+100.
Cardiac disorders Atrial fibrillation	16.7% 1/6 • Number of events 1 • Adverse event collection from the start of preparative regimen up to Day+100.

Additional Information

Richard E. Champlin, MD/Chair, Stem Cell Transplantation

University of Texas (UT) MD Anderson Cancer Center

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place