Phase 1/2 Study of Carfilzomib for the Prevention of Relapse and GVHD in Allo-HCT for Hematologic Malignancies

University of Michigan Rogel Cancer Center

Status and phase

Completed

Phase 2

Phase 1

Conditions

Graft-Versus-Host Disease

Relapse

Hematologic Malignancies

Treatments

Drug: Carfilzomib

Drug: Tacrolimus

Study type

Interventional

Funder types

Other

Identifiers

NCT02145403

HUM00084170 (Other Identifier)

UMCC 2014.010

Details and patient eligibility

About

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.

Enrollment

53 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No Healthy Volunteers

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