Clinical trial NCT02145403: Phase 1/2 Study of Carfilzomib for the Prevention of Relapse and GVHD in Allo-HCT for Hematologic Malignancies
Official title: Phase 1/2 Study of Carfilzomib for the Prevention of Relapse and Graft-versus-host Disease in Allogeneic Hematopoietic Cell Transplantation for High-risk Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hematologic Malignancies
Relapse
Graft-Versus-Host Disease
Keywords: Allogeneic Transplantation
Carfilzomib
Relapse
Graft-Versus-Host Disease
Multiple Myeloma
Lymphoma
Leukemia
Lead sponsor: University of Michigan Rogel Cancer Center
Sponsor class: OTHER
First posted: 2014-05-22
Enrollment: 53
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Phase I: Maximum Tolerated Dose (MTD) of Carfilzomib
timeFrame: Up to day 28
measure: Phase II: Kaplan-Meier Estimate of the Percentage of Patients Who Are Alive and Have Not Developed Any "Event"
timeFrame: 1 year
Secondary outcomes:
measure: Phase II: Kaplan-Meier Estimate for Progression/Relapse-free Survival Time
timeFrame: Up to 3 years
measure: Phase II: Kaplan-Meier Estimate for Overall Survival Time
timeFrame: Up to 3 years
measure: Number of Regimen Related Toxicities (RRTs)
timeFrame: Up to 30 days post treatment
measure: Phase II: Cumulative Incidence of Acute GVHD
timeFrame: At day 180 post-transplant; data collected up to 3 years
measure: Phase II: Cumulative Incidence of Chronic GVHD
timeFrame: Up to 3 years
measure: Phase II: Cumulative Incidence of Non-relapse Mortality
timeFrame: Up to 3 years
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan Hospital
state: Michigan
Study officials:
affiliation: University of Michgan Cancer Center
name: Attaphol Pawarode, M.D.
role: PRINCIPAL_INVESTIGATOR
References: