NCT02145403 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: COMPLETED
Registry last update: 2022-01-03

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Phase I: Maximum Tolerated Dose (MTD) of Carfilzomib

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outcome · POSTED

Phase II: Kaplan-Meier Estimate of the Percentage of Patients Who Are Alive and Have Not Developed Any "Event"

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outcome · POSTED

Phase II: Kaplan-Meier Estimate for Progression/Relapse-free Survival Time

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outcome · POSTED

Phase II: Kaplan-Meier Estimate for Overall Survival Time

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outcome · POSTED

Number of Regimen Related Toxicities (RRTs)

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outcome · POSTED

Phase II: Cumulative Incidence of Acute GVHD

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outcome · POSTED

Phase II: Cumulative Incidence of Chronic GVHD

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outcome · POSTED

Phase II: Cumulative Incidence of Non-relapse Mortality

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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
healthy Volunteers: false
maximum Age: 70 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Carfilzomib will be administered IV over 30 minutes, starting at dose level 1 (20 mg/m2 IV) on Day +1, +2, +6 and +7.
intervention Names
Drug: Carfilzomib
Drug: Tacrolimus
label
Carfilzomib
type
EXPERIMENTAL

interventions

arm Group Labels
Carfilzomib
description
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.
name
Carfilzomib
other Names
Kyprolis®
type
DRUG
arm Group Labels
Carfilzomib
description
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.
name
Tacrolimus
type
DRUG

Study design

allocation

intervention Model

SINGLE_GROUP

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 53
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Phase I: Maximum Tolerated Dose (MTD) of Carfilzomib
time Frame
Up to day 28
description
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.
measure
Phase II: Kaplan-Meier Estimate of the Percentage of Patients Who Are Alive and Have Not Developed Any "Event"
time Frame
1 year

secondary Outcomes

description
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.
measure
Phase II: Kaplan-Meier Estimate for Progression/Relapse-free Survival Time
time Frame
Up to 3 years
description
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.
measure
Phase II: Kaplan-Meier Estimate for Overall Survival Time
time Frame
Up to 3 years
description
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.
measure
Number of Regimen Related Toxicities (RRTs)
time Frame
Up to 30 days post treatment
description
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.
measure
Phase II: Cumulative Incidence of Acute GVHD
time Frame
At day 180 post-transplant; data collected up to 3 years
description
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.
measure
Phase II: Cumulative Incidence of Chronic GVHD
time Frame
Up to 3 years
description
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.
measure
Phase II: Cumulative Incidence of Non-relapse Mortality
time Frame
Up to 3 years

Full study description

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.

Source references

Source notices and limitations

Discovery and provenance

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Preserved source evidence · Not medical advice