Trial Outcomes & Findings for Biparental HLA Haplotype Disparate T-cell Depleted Transplants for Patients Lacking an HLACompatible Donor (NCT NCT01598025)

Last Updated: 2018-08-09

Results Overview

Efficacy is measured by: 1. incidence of transplant-related mortality, overall survival and disease-free survival at 1 year post transplant. 2. incidence, tempo and complications of engraftment and hematopoietic reconstitutions and conversely, the risk of graft failure 3. incidence and severity of acute and/or chronic GVHD 4. incidence and severity of opportunistic infections developing following engraftment

Recruitment status

TERMINATED

Study phase

Target enrollment

3 participants

Primary outcome timeframe

1 year

Results posted on

2018-08-09

Participant Flow

Participant milestones

Participant milestones
Measure	REGIMEN 1 REGIMEN 1: Patients undergo hyperfractionated TBI TID for a total of 11-12 doses on days -10 to -7 and receive thiotepa IV over 4 hours QD on days -6 and -5, fludarabine phosphate IV over 30 minutes QD on days -6 to -2, and anti-thymocyte globulin IV on days -4 to -2. TRANSPLANTATION: Patients undergo CD34-selected allogeneic PBSCT on day 0. total-body irradiation (TBI) thiotepa fludarabine phosphate anti-thymocyte globulin allogeneic hematopoietic stem cell transplantation peripheral blood stem cell transplantation laboratory biomarker analysis	Regimen 2 To be given to patients non-malignant, life-threatening diseases and patients with hematologic malignancies, with extensive prior therapy and comorbidities who are unable to receive TBI, consists of Melphalan 70mg/m2 IV x 2 days, thiotepa 5mg/kg IV x 2 days (or 10mg/kg x 1 day), and fludarabine 25 mg/m2 IV x 5 days. TRANSPLANTATION: Patients undergo CD34-selected allogeneic PBSCT on day 0. thiotepa fludarabine phosphate melphalan anti-thymocyte globulin allogeneic hematopoietic stem cell transplantation peripheral blood stem cell transplantation laboratory biomarker analysis
Overall Study STARTED	0	3
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	0	3

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Biparental HLA Haplotype Disparate T-cell Depleted Transplants for Patients Lacking an HLACompatible Donor

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	REGIMEN 1 REGIMEN 1: Patients undergo hyperfractionated TBI TID for a total of 11-12 doses on days -10 to -7 and receive thiotepa IV over 4 hours QD on days -6 and -5, fludarabine phosphate IV over 30 minutes QD on days -6 to -2, and anti-thymocyte globulin IV on days -4 to -2. TRANSPLANTATION: Patients undergo CD34-selected allogeneic PBSCT on day 0. total-body irradiation (TBI) thiotepa fludarabine phosphate anti-thymocyte globulin allogeneic hematopoietic stem cell transplantation peripheral blood stem cell transplantation laboratory biomarker analysis	Regimen 2 n=3 Participants To be given to patients non-malignant, life-threatening diseases and patients with hematologic malignancies, with extensive prior therapy and comorbidities who are unable to receive TBI, consists of Melphalan 70mg/m2 IV x 2 days, thiotepa 5mg/kg IV x 2 days (or 10mg/kg x 1 day), and fludarabine 25 mg/m2 IV x 5 days. TRANSPLANTATION: Patients undergo CD34-selected allogeneic PBSCT on day 0. thiotepa fludarabine phosphate melphalan anti-thymocyte globulin allogeneic hematopoietic stem cell transplantation peripheral blood stem cell transplantation laboratory biomarker analysis	Total n=3 Participants Total of all reporting groups
Age, Continuous	—	12 years n=7 Participants	12 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1 year

Population: Due to the small accrual on study, as well as patient course following treatment on study, the primary objectives of this study were not able to be analyzed.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 1 year

Population: Due to the small accrual on study, as well as patient course following treatment on study, the primary objectives of this study were not able to be analyzed.

The levels of engraftment and persistence of hematopoietic cells and their myeloid and lymphoid progressing from each donor post transplant. The tolerance or reactivity of engrafted T cells from each donor detected in the blood at 3, 6, and thereafter every 3-6 months until normal, post transplant against host cells and cells derived from the other parent as measured by standard mixed lymphocyte culture and cell mediated cytolysis assays.

Outcome measures

Outcome data not reported

Adverse Events

Regimen 2

Serious events: 2 serious events

Other events: 3 other events

Deaths: 3 deaths

Serious adverse events

Serious adverse events
Measure	Regimen 2 n=3 participants at risk To be given to patients non-malignant, life-threatening diseases and patients with hematologic malignancies, with extensive prior therapy and comorbidities who are unable to receive TBI, consists of Melphalan 70mg/m2 IV x 2 days, thiotepa 5mg/kg IV x 2 days (or 10mg/kg x 1 day), and fludarabine 25 mg/m2 IV x 5 days. TRANSPLANTATION: Patients undergo CD34-selected allogeneic PBSCT on day 0.
Metabolism and nutrition disorders Acidosis	33.3% 1/3 • Up to 24 months after transplant
Respiratory, thoracic and mediastinal disorders Bronchopulmonary hemorrhage	66.7% 2/3 • Up to 24 months after transplant
Vascular disorders Hypotension	33.3% 1/3 • Up to 24 months after transplant
Reproductive system and breast disorders Hypoxia	66.7% 2/3 • Up to 24 months after transplant
General disorders Multi-organ failure	33.3% 1/3 • Up to 24 months after transplant
Infections and infestations Myelitis	33.3% 1/3 • Up to 24 months after transplant
Nervous system disorders Nervous system disorders - Other, specify	33.3% 1/3 • Up to 24 months after transplant
Gastrointestinal disorders Pancreatitis	33.3% 1/3 • Up to 24 months after transplant
Renal and urinary disorders Renal and urinary disorders - Other, specify	33.3% 1/3 • Up to 24 months after transplant
Cardiac disorders Sinus tachycardia	33.3% 1/3 • Up to 24 months after transplant

Other adverse events

Other adverse events
Measure	Regimen 2 n=3 participants at risk To be given to patients non-malignant, life-threatening diseases and patients with hematologic malignancies, with extensive prior therapy and comorbidities who are unable to receive TBI, consists of Melphalan 70mg/m2 IV x 2 days, thiotepa 5mg/kg IV x 2 days (or 10mg/kg x 1 day), and fludarabine 25 mg/m2 IV x 5 days. TRANSPLANTATION: Patients undergo CD34-selected allogeneic PBSCT on day 0.
Investigations Lymphocyte count decreased	100.0% 3/3 • Up to 24 months after transplant
Investigations Platelet count decreased	100.0% 3/3 • Up to 24 months after transplant
Investigations White blood cell decreased	100.0% 3/3 • Up to 24 months after transplant
Blood and lymphatic system disorders Anemia	66.7% 2/3 • Up to 24 months after transplant
Metabolism and nutrition disorders Hypokalemia	66.7% 2/3 • Up to 24 months after transplant
Investigations Neutrophil count decreased	66.7% 2/3 • Up to 24 months after transplant
Investigations Activated partial thromboplastin time prolonged	33.3% 1/3 • Up to 24 months after transplant
Metabolism and nutrition disorders Hyperglycemia	33.3% 1/3 • Up to 24 months after transplant
Metabolism and nutrition disorders Hyperkalemia	33.3% 1/3 • Up to 24 months after transplant
Metabolism and nutrition disorders Hypocalcemia	33.3% 1/3 • Up to 24 months after transplant
Metabolism and nutrition disorders Hypophosphatemia	33.3% 1/3 • Up to 24 months after transplant
Investigations Lipase increased	33.3% 1/3 • Up to 24 months after transplant
Investigations Serum amylase increased	33.3% 1/3 • Up to 24 months after transplant

Additional Information

Dr. Richard O'Reilly, MD

Memorial Sloan Kettering Cancer Center

Phone: 646-888-2157

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place