Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02145403
Other study ID # UMCC 2014.010
Secondary ID HUM00084170
Status Completed
Phase Phase 1/Phase 2
First received
Last updated
Start date October 2014
Est. completion date October 16, 2020

Study information

Verified date December 2021
Source University of Michigan Rogel Cancer Center
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The investigators hypothesize that adding carfilzomib to standard conditioning regimen for allo-HCT for advanced or high-risk hematologic malignancies will decrease post-transplant relapse and treatment-related mortality by decreasing severe GVHD, leading to overall improvement in transplant outcomes.


Recruitment information / eligibility

Status Completed
Enrollment 53
Est. completion date October 16, 2020
Est. primary completion date November 26, 2018
Accepts healthy volunteers No
Gender All
Age group 18 Years to 70 Years
Eligibility Inclusion Criteria: - Lymphoid or Myeloid malignancy requiring allogeneic hematopoietic cell transplantation - Pathology review by the study institution is required - Prior high-dose chemotherapy and autologous HCT(s) is (are) allowed - Disease status: Stable disease or better at the time of enrollment - Age: >18 and <70 years old at the time of transplant (< 71 years at transplant admission) - Life expectancy = 6 months after transplant - A 8/8 or 7/8 HLA-matched donor is available - Karnofsky Performance Status >70% (A measure of quality of life that ranges from 0 to 100 where 100 equals perfect health and 0 is death.) - Adequate cardiac [LVEF (Left Ventricular Ejection Fraction) >0.4], pulmonary [FEV1 (Forced Expiratory Volume in 1 Second), FVC (Forced Vital Capacity), corrected DLCO (Diffusing Capacity) = 50% predicted], hepatic [DB (Direct Bilirubin) <1.5xULN, AST (Aspartate Aminotransferase) / ALT (Alanine transaminase) =3xULN] and renal function [GFR (Glomerular Filtration Rate) = 60 mL/min/1.73 m2] Exclusion Criteria: - Progressive disease - Active central nervous system involvement by malignancy - Non compliance to medications or medical instructions - Lack of appropriate caregivers - Life expectancy <6 months - Pregnant or lactating females - Uncontrolled infection requiring active treatment (systemic antibiotics, anti-virals, or anti-fungals) within 14 days - HIV-1/HIV-2 or HTLV-1/HTLV-2 seropositivity - Active hepatitis A, B or C infection - Unstable angina or myocardial infarction within 6 months prior to randomization, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, uncontrolled or persistent atrial fibrillation/flutter, history of ventricular fibrillation, ventricular tachycardia/torsade de pointes, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker - History of pulmonary hypertension - Uncontrolled hypertension or uncontrolled diabetes mellitus - Non-hematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen (PSA) levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localized transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas - Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib) - Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all available anti-microbial drugs or intolerance to IV hydration due to pre-existing pulmonary or cardiac impairment - Subjects with pleural effusion requiring thoracentesis or ascites requiring paracentesis within 14 days prior to admission - Uncontrolled psychiatric condition - Any other clinically significant medical or psychiatric disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent

Study Design


Intervention

Drug:
Carfilzomib
Carfilzomib will be administered starting at dose level 1 (20 mg/m2 IV) on day +1, +2, +6 and +7. Dose escalation will be performed on the day +6 and day +7 doses only in each dose level. Day +1 and day+2 doses will be fixed at 20 mg/m2 IV in all dose levels.
Tacrolimus
Tacrolimus will be administered at 0.03 mg/kg continuous infusion over 24 hours, starting on day -3 as standard graft-versus-host disease prophylaxis.

Locations

Country Name City State
United States University of Michigan Hospital Ann Arbor Michigan

Sponsors (1)

Lead Sponsor Collaborator
University of Michigan Rogel Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Phase I: Maximum Tolerated Dose (MTD) of Carfilzomib Subjects were enrolled on the first dose level (20 mg/m^2), following a standard 3+3 dose escalation. For any given dose level, if none of the 3 subjects developed a treatment-related dose limiting toxicity (DLT), defined per protocol, dose escalation would follow. If a DLT occurred in any given dose level, the cohort would be expanded to 6. Further dose escalation would be made only if DLTs occurred in <2 out of 6 subjects. If >=2 of 6 develop DLTs, dose de-escalation would be made to the previous level. The highest dose level at which no more than one of six participants experience a DLT defines the MTD. Up to day 28
Primary Phase II: Kaplan-Meier Estimate of the Percentage of Patients Who Are Alive and Have Not Developed Any "Event" Kaplan-Meier estimate of the percentage of patients who are alive and have not developed relapse/progression of primary disease or clinical grade III-IV acute graft-versus- host disease (GVHD) or chronic GVHD requiring systemic treatment. Subjects who receive all 4 doses of carfilzomib at the maximum tolerated dose level will be considered evaluable for endpoint analysis. 1 year
Secondary Phase II: Kaplan-Meier Estimate for Progression/Relapse-free Survival Time Time from day 0 to the date of the first progression/relapse. Subjects who receive all 4 doses of carfilzomib at the maximum tolerated dose level will be considered evaluable for endpoint analysis. Up to 3 years
Secondary Phase II: Kaplan-Meier Estimate for Overall Survival Time The time from day 0 to the day of death from any cause. Subjects who receive all 4 doses of carfilzomib at the maximum tolerated dose level will be considered evaluable for endpoint analysis. Up to 3 years
Secondary Number of Regimen Related Toxicities (RRTs) An RTT is defined as an adverse event (AE) that occurs within +37 days after transplant or 30 days after the last dose of carfilzomib (day +7), and is considered to be a direct consequence and a related event as a result of the combination of conditioning chemotherapy, GVHD prophylaxis regimen and carfilzomib. Up to 30 days post treatment
Secondary Phase II: Cumulative Incidence of Acute GVHD The cumulative incidence of acute Graft Versus Host Disease (aGVHD). Events were assigned a severity grade using the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI CTCAE) v. 4.0; lower values indicate least severe and higher values indicate most severe. Grades 2 - 4 and grades 3 - 4 events are reported. Subjects who receive all 4 doses of carfilzomib at the maximum tolerated dose level will be considered evaluable for endpoint analysis. At day 180 post-transplant; data collected up to 3 years
Secondary Phase II: Cumulative Incidence of Chronic GVHD The cumulative incidence of chronic Graft Versus Host Disease (GVHD). Subjects who receive all 4 doses of carfilzomib at the maximum tolerated dose level will be considered evaluable for endpoint analysis. Up to 3 years
Secondary Phase II: Cumulative Incidence of Non-relapse Mortality The cumulative incidence of non-relapse mortality. Subjects who receive all 4 doses of carfilzomib at the maximum tolerated dose level will be considered evaluable for endpoint analysis. Up to 3 years
See also
  Status Clinical Trial Phase
Recruiting NCT05433090 - An Inpatient Advance Care Planning Intervention for Older Patients With Hematologic Malignancies N/A
Completed NCT00061620 - Phase I Study of Continuous Infusion Schedule of FMdC in Hematologic Malignancies Phase 1
Enrolling by invitation NCT02473757 - Gene Therapy Follow-up Protocol for People Previously Enrolled in CAR-T Cell Studies
Not yet recruiting NCT06296368 - DISCOVERY: Evaluating a Decision Support Tool for Adults Seen in Hematology/Oncology Clinics N/A
Recruiting NCT02032446 - Umbilical Cord Derived Mesenchymal Stromal Cells For The Treatment of Severe Steroid-resistant Graft Versus Host Disease Phase 1/Phase 2
Recruiting NCT02884375 - Elderly CAncer Patient N/A
Recruiting NCT01203722 - Reduced Intensity, Partially HLA Mismatched BMT to Treat Hematologic Malignancies Phase 1/Phase 2
Completed NCT00780052 - Infusional C-myb ASODN in Advanced Hematologic Malignancies Phase 1
Recruiting NCT04098393 - Giving Chemotherapy for a Shortened Amount of Time Before a Stem Cell Transplantation Phase 1
Recruiting NCT06028828 - Risk-ADAPTed Conditioning Regimen for Allogeneic Hematopoietic Stem Cell Transplantation Phase 2
Completed NCT04538599 - RD13-01 for Patients With r/r CD7+ T/NK Cell Hematologic Malignancies Phase 1
Completed NCT03609827 - Study of Melphalan Drug Exposure in Pediatric Hematopoietic Stem Cell Transplant Patients
Completed NCT01380756 - Study Evaluating Orally Administered AMG 900 in Adult Subjects With Acute Myeloid Leukemia Phase 1
Recruiting NCT05849207 - Post-Transplant Cyclophosphamide in Patients Aged >/= 70 Years Undergoing Haploidentical Transplant Phase 1
Not yet recruiting NCT05028478 - A Study of CN202 in Adult Subjects With Locally Advanced or Metastatic Solid Tumors or Hematologic Malignancies Phase 1/Phase 2
Active, not recruiting NCT02494258 - A Study to Evaluate Long-term Safety of CC-486 (Oral Azacitidine) in Subjects With Hematological Disorders Phase 2
Completed NCT03212560 - Exercise Capacity and Physical Activity Levels in Newly Diagnosed Hematologic Malignant Patients
Active, not recruiting NCT02600208 - Peripheral Blood Stem Cell Transplantation for Hematologic Malignancies With Alpha Beta TCell and B Cell Depletion Using the CliniMACS Device Phase 2/Phase 3
Completed NCT01949545 - Study of the Pharmacokinetics and Safety of Carfilzomib in Patients With Advanced Malignancies and Hepatic Impairment Phase 1
Completed NCT01930981 - Associations Between Pre-transplant Comorbidities and Post-transplant Toxicities and Quality of Life N/A