Trial Outcomes & Findings for Antithymocyte Globulin, Clofarabine, and Rituximab in Treating Patients After an Unsuccessful Stem Cell Transplant (NCT NCT00617929)

Last Updated: 2017-12-28

Results Overview

Rate of Sustained Donor Engraftment is defined as the percent of paticipants with an absolute neutrophile count (ANC) of 500 or more without a subsequent graft rejection.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

12 participants

Primary outcome timeframe

Day 42 post transplantation

Results posted on

2017-12-28

Participant Flow

Participant milestones

Participant milestones
Measure	Conditioning for Graft Failure After Transplant Day -7: Rituximab 375 mg/m2 Day -6: Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -5: Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -4: Clofarabine 30 mg/m2 IV over 1 hour and Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -3: Clofarabine 30 mg/m2 IV over 1 hour Day -2: Clofarabine 30 mg/m2 IV over 1 hour Day -1: Rest Day 0: Stem Cell Infusion
Overall Study STARTED	12
Overall Study COMPLETED	11
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Conditioning for Graft Failure After Transplant Day -7: Rituximab 375 mg/m2 Day -6: Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -5: Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -4: Clofarabine 30 mg/m2 IV over 1 hour and Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -3: Clofarabine 30 mg/m2 IV over 1 hour Day -2: Clofarabine 30 mg/m2 IV over 1 hour Day -1: Rest Day 0: Stem Cell Infusion
Overall Study Physician Decision	1

Baseline Characteristics

Antithymocyte Globulin, Clofarabine, and Rituximab in Treating Patients After an Unsuccessful Stem Cell Transplant

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Conditioning for Graft Failure After Transplant n=12 Participants Day -7: Rituximab 375 mg/m2 Day -6: Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -5: Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -4: Clofarabine 30 mg/m2 IV over 1 hour and Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -3: Clofarabine 30 mg/m2 IV over 1 hour Day -2: Clofarabine 30 mg/m2 IV over 1 hour Day -1: Rest Day 0: Stem Cell Infusion
Age, Categorical <=18 years	6 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 42 post transplantation

Rate of Sustained Donor Engraftment is defined as the percent of paticipants with an absolute neutrophile count (ANC) of 500 or more without a subsequent graft rejection.

Outcome measures

Outcome measures
Measure	Conditioning for Graft Failure After Transplant n=11 Participants Day -7: Rituximab 375 mg/m2 Day -6: Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -5: Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -4: Clofarabine 30 mg/m2 IV over 1 hour and Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -3: Clofarabine 30 mg/m2 IV over 1 hour Day -2: Clofarabine 30 mg/m2 IV over 1 hour Day -1: Rest Day 0: Stem Cell Infusion
Rate of Sustained Donor Engraftment	73 percentage of participants

PRIMARY outcome

Timeframe: Day 100 post transplantation

Percent of patients alive from beginning of study to Day 100 post transplantation

Outcome measures

Outcome measures
Measure	Conditioning for Graft Failure After Transplant n=11 Participants Day -7: Rituximab 375 mg/m2 Day -6: Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -5: Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -4: Clofarabine 30 mg/m2 IV over 1 hour and Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -3: Clofarabine 30 mg/m2 IV over 1 hour Day -2: Clofarabine 30 mg/m2 IV over 1 hour Day -1: Rest Day 0: Stem Cell Infusion
Survival at 100 Days Post Transplant	73 percentage of participants

SECONDARY outcome

Timeframe: Day 100 post transplantation

Percent of patients who died related to the treatment in this study.

Outcome measures

Outcome measures
Measure	Conditioning for Graft Failure After Transplant n=11 Participants Day -7: Rituximab 375 mg/m2 Day -6: Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -5: Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -4: Clofarabine 30 mg/m2 IV over 1 hour and Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -3: Clofarabine 30 mg/m2 IV over 1 hour Day -2: Clofarabine 30 mg/m2 IV over 1 hour Day -1: Rest Day 0: Stem Cell Infusion
Treatment-related Death	18 percentage of participants

SECONDARY outcome

Timeframe: Day 42 post transplantation

Time to primary neutrophil engraftment is defined as the percent of patients with an absolute neutrophil count (ANC) of 500 or more neutrophils in a cubic millimeter of blood.

Outcome measures

Outcome measures
Measure	Conditioning for Graft Failure After Transplant n=11 Participants Day -7: Rituximab 375 mg/m2 Day -6: Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -5: Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -4: Clofarabine 30 mg/m2 IV over 1 hour and Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -3: Clofarabine 30 mg/m2 IV over 1 hour Day -2: Clofarabine 30 mg/m2 IV over 1 hour Day -1: Rest Day 0: Stem Cell Infusion
Time to Primary Neutrophil Engraftment	73 percentage of participants

SECONDARY outcome

Timeframe: One year post transplantation

Percent of patients alive from beginning of study to one year post transplantation

Outcome measures

Outcome measures
Measure	Conditioning for Graft Failure After Transplant n=11 Participants Day -7: Rituximab 375 mg/m2 Day -6: Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -5: Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -4: Clofarabine 30 mg/m2 IV over 1 hour and Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -3: Clofarabine 30 mg/m2 IV over 1 hour Day -2: Clofarabine 30 mg/m2 IV over 1 hour Day -1: Rest Day 0: Stem Cell Infusion
Survival	36 percentage of participants

SECONDARY outcome

Timeframe: Day 28 post transplantation

Occurrence of genetically distinct cell types in a single organism

Outcome measures

Outcome measures
Measure	Conditioning for Graft Failure After Transplant n=11 Participants Day -7: Rituximab 375 mg/m2 Day -6: Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -5: Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -4: Clofarabine 30 mg/m2 IV over 1 hour and Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -3: Clofarabine 30 mg/m2 IV over 1 hour Day -2: Clofarabine 30 mg/m2 IV over 1 hour Day -1: Rest Day 0: Stem Cell Infusion
Chimerism	95 percentage of donor cells Interval 0.0 to 100.0

SECONDARY outcome

Timeframe: Day 30-100

Percent of patients with Acute Graft-vs-host Disease - a process where T-cells present in the donor's bone marrow at the time of transplant identify the transplant patient as "non-self' and attack the patient's skin, liver, stomach, and/or intestines.

Outcome measures

Outcome measures
Measure	Conditioning for Graft Failure After Transplant n=11 Participants Day -7: Rituximab 375 mg/m2 Day -6: Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -5: Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -4: Clofarabine 30 mg/m2 IV over 1 hour and Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -3: Clofarabine 30 mg/m2 IV over 1 hour Day -2: Clofarabine 30 mg/m2 IV over 1 hour Day -1: Rest Day 0: Stem Cell Infusion
Acute Graft-vs-host Disease	18 percentage of participants

Adverse Events

Conditioning for Graft Failure After Transplant

Serious events: 7 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Conditioning for Graft Failure After Transplant n=11 participants at risk Day -7: Rituximab 375 mg/m2 Day -6: Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -5: Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -4: Clofarabine 30 mg/m2 IV over 1 hour and Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -3: Clofarabine 30 mg/m2 IV over 1 hour Day -2: Clofarabine 30 mg/m2 IV over 1 hour Day -1: Rest Day 0: Stem Cell Infusion
Injury, poisoning and procedural complications Graft failure	27.3% 3/11
Blood and lymphatic system disorders Febrile neutropenia	9.1% 1/11
General disorders Multi-system organ failure	18.2% 2/11
Infections and infestations Infection	9.1% 1/11
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm, malignant	9.1% 1/11

Other adverse events

Other adverse events
Measure	Conditioning for Graft Failure After Transplant n=11 participants at risk Day -7: Rituximab 375 mg/m2 Day -6: Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -5: Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -4: Clofarabine 30 mg/m2 IV over 1 hour and Antithymocyte globulin (Thymoglobulin) 3 mg/kg IV over 4 hours Day -3: Clofarabine 30 mg/m2 IV over 1 hour Day -2: Clofarabine 30 mg/m2 IV over 1 hour Day -1: Rest Day 0: Stem Cell Infusion
Nervous system disorders Peripheral neuropathy	9.1% 1/11
Renal and urinary disorders Renal failure	45.5% 5/11
Respiratory, thoracic and mediastinal disorders Respiratory distress	18.2% 2/11
Cardiac disorders Tachycardia	9.1% 1/11
Gastrointestinal disorders Esophageal necrosis	9.1% 1/11
Gastrointestinal disorders Gastrointestinal bleed	45.5% 5/11
Hepatobiliary disorders Cholangitis	9.1% 1/11
Musculoskeletal and connective tissue disorders Aseptic/avascular necrosis	9.1% 1/11
Psychiatric disorders Anxiety attacks	9.1% 1/11
General disorders Pain NOS	9.1% 1/11
Respiratory, thoracic and mediastinal disorders Pneumonia	72.7% 8/11
Nervous system disorders Encephalopathy	9.1% 1/11
Infections and infestations Osteomyelitis	9.1% 1/11
Vascular disorders Small vessel ischemia disease	9.1% 1/11
Renal and urinary disorders Cystitis	18.2% 2/11
Nervous system disorders Pseudotumor cerebri	9.1% 1/11
Cardiac disorders Bradycardia	9.1% 1/11
Endocrine disorders Adrenal insufficiency	9.1% 1/11
Infections and infestations Gastrointestinal infection	9.1% 1/11
Infections and infestations Bacteremia	18.2% 2/11
Infections and infestations Sepsis	9.1% 1/11
Infections and infestations Skin infection	9.1% 1/11
Nervous system disorders Hyperdense focus in parietal lobe of brain	9.1% 1/11
Nervous system disorders Decreased brain volume	9.1% 1/11
Cardiac disorders Pericardial effusion	9.1% 1/11
Gastrointestinal disorders Ileus	9.1% 1/11
Vascular disorders Capillary leak syndrome	9.1% 1/11
Gastrointestinal disorders Partial small bowel obstruction	9.1% 1/11
Infections and infestations Viremia	9.1% 1/11
Vascular disorders Veno-occlusive disease	9.1% 1/11
Nervous system disorders Hydrocephalus	9.1% 1/11
Skin and subcutaneous tissue disorders Stevens Johnson syndrome	9.1% 1/11
Infections and infestations Vancomycin-resistant enterococci	9.1% 1/11
Gastrointestinal disorders Multi-system organ failure	9.1% 1/11
Cardiac disorders Supraventricular tachycardia	9.1% 1/11
Vascular disorders Deep vein thrombosis vs. cellulitis	9.1% 1/11
Eye disorders Eye hemorrhage	9.1% 1/11
Respiratory, thoracic and mediastinal disorders Pulmonary hemorrhage	18.2% 2/11
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	9.1% 1/11
Vascular disorders Hypertension	9.1% 1/11
Metabolism and nutrition disorders Hyperglycemia	9.1% 1/11
Renal and urinary disorders Hemorrhagic cystitis	9.1% 1/11

Additional Information

Jakub Tolar, MD

Masonic Cancer Center, University of Minnesota

Phone: 612-624-7180

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place