Multicenter Phase II of CD26 Using Sitagliptin for Engraftment After UBC Transplant

• Sponsor: Sherif S. Farag (Other)
• Overall Status: Completed
• CT.gov ID: NCT01720264
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 15
• Locations: 2
• Arm: 1
• Actual Duration (Months): 61.4
• Patients Per Site: 7.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The main purpose of this trial is to assess the efficacy and safety of sitagliptin in enhancing engraftment following umbilical cord blood transplantation (recovery of blood counts after transplant).

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia; Acute Lymphoid Leukemia; Hematopoetic Myelodysplasia; Leukemia, Myelogenous, Chronic; Lymphoma, Non-Hodgkin	Drug: Sitagliptin	Phase 2

Detailed Description

Umbilical cord blood (UCB) is more commonly used for transplantation in children but is being used in adults more often. However, because adults are larger than children, the relatively smaller stem cell dose in UCB is major limitation for transplantation in adults and engraftment can be delayed. This study is trying to find out if the drug sitagliptin can be used to increase and speed up engraftment in adults receiving UCB transplantation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter Phase II Trial of Inhibition of CD26 Peptidase Using Sitagliptin to Enhance Engraftment After Umbilical Cord Blood Transplantation for Adults With Hematological Malignancies
• Actual Study Start Date: Nov 2, 2012
• Actual Primary Completion Date: Aug 27, 2016
• Actual Study Completion Date: Dec 15, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sitagliptin Sitagliptin q 12 hours PO starting on Day -1 then given every 12 hours (total 10 doses) on Day 0, Day +1, +2 and Day +3.	Drug: Sitagliptin; Sitagliptin q 12 hours PO starting on Day -1 then given every 12 hours (total 10 doses) on Day 0, Day +1, +2 and Day +3.; Other Names: Januvia

Outcome Measures

Primary Outcome Measures

1. The Percent of Subjects Engrafting by Day +30 After Transplantation [Day 0 to Day +30 post transplant]

   Percent of patients and the 95% Binomial Confidence interval who were able to achieve neutrophils engraftment (defined as the date of the first of three consecutive ANC values obtained on different days after transplantation during which the absolute neutrophils count (ANC) is at least 0.5 x109/l) by 30 days following transplant.

Secondary Outcome Measures

1. Time to Neutrophil Engraftment [Transplant (Day 0) up to 1 year]

   Time to neutrophil engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of neutrophils is defined as the time from day 0 to the date of the first of three consecutive days after transplantation during which the absolute neutrophils count (ANC) is at least 0.5 x109/l. Patients surviving at least 14 days after transplant will be evaluable for this endpoint. Patients who did not have neutrophil engraftment before death will be censored at the date of death. The median and 95% confidence intervals will be provided.

2. Time to Platelet Engraftment [Transplant (Day 0) up to 1 year]

   Time to platelet engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of platelets is defined as the time from day 0 to the first of three consecutive Complete Blood Counts (CBCs) obtained on different days after transplantation during which the platelet count is at least 20 x109/l. The CBCs obtained should be at least seven days after the most recent platelet transfusion. Only patients who achieved engraftment of platelets will be included in the analysis. The median and 95% confidence intervals will be provided.

3. Number of Subjects With Treatment Related Adverse Events Grade 3 and 4 Non-hematological Toxicities [Day 0 up to 3 years]

   Number of unique patients who had a treatment related (possible, probable or definite) non-hematological adverse event that was graded 3 or greater.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients must have one of the following disease types:

• Acute myeloid leukemia (AML) with disease features as described in the protocol.

• Acute lymphoblastic leukemia (ALL) with disease features as described in the protocol.

• Myelodysplasia with disease features as described in the protocol.

• Chronic myelogenous leukemia (CML) with disease features as described in the protocol.

• Patients with aggressive non-Hodgkin's lymphoma (NHL), including diffuse large cell lymphoma, mediastinal B-cell lymphoma, transformed lymphoma, mantle cell lymphoma, and peripheral T cell lymphoma, who also have one of the disease features as described in the protocol.

• At least 35 days following start of preceding leukemia induction cytotoxic chemotherapy.

• For patients in remission, there should be no readily available consenting HLA-matched related donor who is either matched fully matched or mismatched at only one locus of HLA-A, -B, and DRB1.

• No availability of a readily available HLA-matched volunteer unrelated donor (8 of 8 allele match at HLA-A, -B, -C and -DRB1).

• Patients must have a matched or partially matched UCB unit with >/= 2.5 x10^7 nucleated cells/kg of recipient weight at the time of cryopreservation.

• No current uncontrolled bacterial, viral or fungal infection (defined as currently taking medication and progression of clinical symptoms).

• No HIV disease.

• Non pregnant and non-nursing.

• Required baseline laboratory values as described in the protocol.

• Signed written informed consent.

Exclusion Criteria:

• Symptomatic uncontrolled coronary artery disease or congestive heart failure.

• Severe hypoxemia with room air PaO2<70, supplemental oxygen dependence, or DLCO<50% predicted.

• Patients with central nervous system (CNS) involvement refractory to intrathecal chemotherapy.

• Prior allogeneic or autologous hematopoietic stem cell transplant in the last 6 months.

• Patients who are taking other insulin secretagogues and/or insulin.

• Patients who have hypersensitivity to sitagliptin.

• Patients with a history of pancreatitis, cholelithiasis, alcoholism, or fasting hypertriglyceridemia (> 2 x ULN).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana	United States	46202
2	New York Medical College/Westchester Medical Center/Maria Fareri Children's Hosptial	Valhalla	New York	United States	10595

Sponsors and Collaborators

• Sherif S. Farag
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Sherif S Farag, MBBS, PhD, Indiana University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sherif S. Farag, Lawrence H. Einhorn Professor of Oncology, Indiana University
• ClinicalTrials.gov Identifier: NCT01720264
• Other Study ID Numbers: 1208009261; HL112669; 1R01HL112669-01
• First Posted: Nov 2, 2012
• Last Update Posted: Jan 8, 2019
• Last Verified: Dec 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Leukemia; Lymphoma, Non-Hodgkin; Leukemia, Lymphoid; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myelodysplastic Syndromes; Sitagliptin Phosphate

Study Results

Participant Flow

Recruitment Details	The study was stopped at 15 patients due to poor accrual. One patient subsequently found not to have met eligibility because she commenced treatment one day earlier than the prescribed 35-day interval from previous therapy is included in the analysis.

Arm/Group Title	Sitagliptin
Arm/Group Description	Sitagliptin 600 mg q 12 hours PO for a total of 10 doses plus Total Body Irradiation (TBI) or Chemotherapy only.
Period Title: Transplant With Sitagliptin for 15 Days
STARTED	15
COMPLETED	14
NOT COMPLETED	1
Period Title: Transplant With Sitagliptin for 15 Days
STARTED	14
COMPLETED	2
NOT COMPLETED	12

Baseline Characteristics

Arm/Group Title	Sitagliptin
Arm/Group Description	Sitagliptin 600 mg q 12 hours PO for a total of 10 doses plus Total Body Irradiation or Chemotherapy only.
Overall Participants	15
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	15 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	40.9 (13.96)
Sex: Female, Male (Count of Participants)
Female	9 60%
Male	6 40%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 6.7%
Not Hispanic or Latino	14 93.3%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	1 6.7%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	4 26.7%
White	10 66.7%
More than one race	0 0%
Unknown or Not Reported	0 0%

Outcome Measures

1. Primary Outcome

Title	The Percent of Subjects Engrafting by Day +30 After Transplantation
Description	Percent of patients and the 95% Binomial Confidence interval who were able to achieve neutrophils engraftment (defined as the date of the first of three consecutive ANC values obtained on different days after transplantation during which the absolute neutrophils count (ANC) is at least 0.5 x109/l) by 30 days following transplant.
Time Frame	Day 0 to Day +30 post transplant

Outcome Measure Data

Analysis Population Description

All patients who received treatment and were followed after transplant.

Arm/Group Title	Sitagliptin
Arm/Group Description	Sitagliptin 600 mg q 12 hours PO for a total of 10 doses plus Total Body Irradiation or Chemotherapy only.
Measure Participants	15
Number (95% Confidence Interval) [percentage of participants]	100 666.7%

2. Secondary Outcome

Title	Time to Neutrophil Engraftment
Description	Time to neutrophil engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of neutrophils is defined as the time from day 0 to the date of the first of three consecutive days after transplantation during which the absolute neutrophils count (ANC) is at least 0.5 x109/l. Patients surviving at least 14 days after transplant will be evaluable for this endpoint. Patients who did not have neutrophil engraftment before death will be censored at the date of death. The median and 95% confidence intervals will be provided.
Time Frame	Transplant (Day 0) up to 1 year

Outcome Measure Data

Analysis Population Description

All patients who received treatment and survived at least 14 days after transplant.

Arm/Group Title	Sitagliptin
Arm/Group Description	Sitagliptin 600 mg q 12 hours PO for a total of 10 doses plus Total Body Irradiation or Chemotherapy only.
Measure Participants	15
Median (95% Confidence Interval) [days]	19

3. Secondary Outcome

Title	Time to Platelet Engraftment
Description	Time to platelet engraftment will be analyzed by the Kaplan-Meier method. The time to engraftment of platelets is defined as the time from day 0 to the first of three consecutive Complete Blood Counts (CBCs) obtained on different days after transplantation during which the platelet count is at least 20 x109/l. The CBCs obtained should be at least seven days after the most recent platelet transfusion. Only patients who achieved engraftment of platelets will be included in the analysis. The median and 95% confidence intervals will be provided.
Time Frame	Transplant (Day 0) up to 1 year

Outcome Measure Data

Analysis Population Description

All patients who received treatment and who achieved platelet recovery/engraftment of platelets.

Arm/Group Title	Sitagliptin
Arm/Group Description	Sitagliptin 600 mg q 12 hours PO for a total of 10 doses plus Total Body Irradiation or Chemotherapy only.
Measure Participants	6
Median (95% Confidence Interval) [days]	52

4. Secondary Outcome

Title	Number of Subjects With Treatment Related Adverse Events Grade 3 and 4 Non-hematological Toxicities
Description	Number of unique patients who had a treatment related (possible, probable or definite) non-hematological adverse event that was graded 3 or greater.
Time Frame	Day 0 up to 3 years

Outcome Measure Data

Analysis Population Description

All patients enrolled and received treatment.

Arm/Group Title	Sitagliptin
Arm/Group Description	Sitagliptin 600 mg q 12 hours PO for a total of 10 doses plus Total Body Irradiation or Chemotherapy only.
Measure Participants	15
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	Up to 3 years
Arm/Group Title	Sitagliptin
Arm/Group Description	Sitagliptin 600 mg q 12 hours PO for a total of 10 doses plus Total Body Irradiation or Chemotherapy only.
All Cause Mortality
	Sitagliptin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Sitagliptin
	Affected / at Risk (%)	# Events
Total	9/15 (60%)
Cardiac disorders
Cardiac arrest	1/15 (6.7%)
Gastrointestinal disorders
Colitis	1/15 (6.7%)
Oral pain	1/15 (6.7%)
General disorders
Multi-organ failure	2/15 (13.3%)
Infections and infestations
Hepatitis viral	1/15 (6.7%)
Infections and infestations - Other	3/15 (20%)
Meningitis	1/15 (6.7%)
Sepsis	2/15 (13.3%)
Metabolism and nutrition disorders
Acidosis	1/15 (6.7%)
Anorexia	1/15 (6.7%)
Dehydration	1/15 (6.7%)
Nervous system disorders
Hydrocephalus	1/15 (6.7%)
Renal and urinary disorders
Acute kidney injury	1/15 (6.7%)
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	1/15 (6.7%)
Hypoxia	1/15 (6.7%)
Pharyngeal mucositis	1/15 (6.7%)
Pulmonary edema	1/15 (6.7%)
Respiratory failure	2/15 (13.3%)
Respiratory, thoracic and mediastinal disorders - Other	1/15 (6.7%)
Vascular disorders
Capillary leak syndrome	1/15 (6.7%)
Other (Not Including Serious) Adverse Events
	Sitagliptin
	Affected / at Risk (%)	# Events
Total	15/15 (100%)
Blood and lymphatic system disorders
Anemia	2/15 (13.3%)
Disseminated intravascular coagulation	1/15 (6.7%)
Febrile neutropenia	1/15 (6.7%)
Cardiac disorders
Atrial fibrillation	1/15 (6.7%)
Cardiac disorders - Other	1/15 (6.7%)
Heart failure	1/15 (6.7%)
Pericardial effusion	1/15 (6.7%)
Sinus bradycardia	2/15 (13.3%)
Sinus tachycardia	1/15 (6.7%)
Ventricular arrhythmia	1/15 (6.7%)
Gastrointestinal disorders
Abdominal pain	1/15 (6.7%)
Diarrhea	2/15 (13.3%)
Enterocolitis	1/15 (6.7%)
Gastrointestinal disorders - Other	1/15 (6.7%)
Lower gastrointestinal hemorrhage	1/15 (6.7%)
Mucositis oral	9/15 (60%)
Nausea	1/15 (6.7%)
Oral pain	1/15 (6.7%)
Vomiting	1/15 (6.7%)
General disorders
Edema limbs	1/15 (6.7%)
Fever	3/15 (20%)
Localized edema	2/15 (13.3%)
Hepatobiliary disorders
Hepatobiliary disorders - Other	2/15 (13.3%)
Infections and infestations
Bladder infection	1/15 (6.7%)
Encephalitis infection	1/15 (6.7%)
Infections and infestations - Other	10/15 (66.7%)
Lung infection	2/15 (13.3%)
Rhinitis infective	1/15 (6.7%)
Salivary gland infection	1/15 (6.7%)
Sepsis	2/15 (13.3%)
Sinusitis	1/15 (6.7%)
Upper respiratory infection	2/15 (13.3%)
Urinary tract infection	3/15 (20%)
Investigations
Alanine aminotransferase increased	1/15 (6.7%)
Alkaline phosphatase increased	2/15 (13.3%)
Aspartate aminotransferase increased	3/15 (20%)
Blood bilirubin increased	6/15 (40%)
Creatinine increased	2/15 (13.3%)
Neutrophil count decreased	2/15 (13.3%)
Platelet count decreased	2/15 (13.3%)
Weight loss	1/15 (6.7%)
Metabolism and nutrition disorders
Anorexia	5/15 (33.3%)
Hyperglycemia	2/15 (13.3%)
Hypokalemia	2/15 (13.3%)
Musculoskeletal and connective tissue disorders
Bone pain	1/15 (6.7%)
Pain in extremity	1/15 (6.7%)
Nervous system disorders
Encephalopathy	3/15 (20%)
Hydrocephalus	1/15 (6.7%)
Intracranial hemorrhage	1/15 (6.7%)
Nervous system disorders - Other	1/15 (6.7%)
Seizure	1/15 (6.7%)
Stroke	1/15 (6.7%)
Syncope	1/15 (6.7%)
Psychiatric disorders
Anxiety	1/15 (6.7%)
Renal and urinary disorders
Acute kidney injury	3/15 (20%)
Hematuria	2/15 (13.3%)
Reproductive system and breast disorders
Menorrhagia	1/15 (6.7%)
Respiratory, thoracic and mediastinal disorders
Adult respiratory distress syndrome	1/15 (6.7%)
Aspiration	1/15 (6.7%)
Dyspnea	2/15 (13.3%)
Hypoxia	5/15 (33.3%)
Laryngeal inflammation	1/15 (6.7%)
Pleural effusion	1/15 (6.7%)
Pneumonitis	1/15 (6.7%)
Pulmonary edema	2/15 (13.3%)
Respiratory failure	1/15 (6.7%)
Respiratory, thoracic and mediastinal disorders - Other	1/15 (6.7%)
Skin and subcutaneous tissue disorders
Pruritus	1/15 (6.7%)
Rash maculo-papular	1/15 (6.7%)
Vascular disorders
Hypotension	5/15 (33.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.