Hematologic MalignanciesPhase 1/2NCT02145403

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

A Phase 1/2 study testing Carfilzomib and Tacrolimus in people with Hematologic Malignancies and Relapse, run by University of Michigan Rogel Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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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. Read more about this study

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Hematologic Malignancies, Relapse, Graft-Versus-Host Disease
What is being tested?: Carfilzomib and Tacrolimus
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 53 participants
Where: 1 siteUnited States
Study dates: Oct 2014to 16 Oct 2020
Phase: Phase 1/2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

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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]

Who cannot join

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

Show all 18Show fewer

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

Trial locations and contacts

1 site in 1 country.

United States1 site

University of Michigan Hospital
Ann Arbor, Michigan, 48109

Other trials in United States

About this study

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

Conditions: Hematologic Malignancies, Relapse, Graft-Versus-Host Disease
Being tested: Carfilzomib, Tacrolimus
Keywords: Allogeneic Transplantation, Carfilzomib, Relapse, Graft-Versus-Host Disease, Multiple Myeloma, Lymphoma, Leukemia
Medical subject headings: Hematologic Neoplasms, Recurrence, Graft vs Host Disease, Multiple Myeloma, Lymphoma, Leukemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

CarfilzomibDrug
Also called Kyprolis®
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.
TacrolimusDrug
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.

Study groups in NCT02145403
Study group	Role	What they receive
Carfilzomib	Experimental	Carfilzomib will be administered IV over 30 minutes, starting at dose level 1 (20 mg/m2 IV) on Day +1, +2, +6 and +7. Receives: Drug: Carfilzomib; Drug: Tacrolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Up to day 28
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.
Measured: 1 year

Secondary outcomes (6)

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.
Measured: Up to 3 years
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.
Measured: Up to 3 years
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.
Measured: Up to 30 days post treatment
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.
Measured: At day 180 post-transplant; data collected up to 3 years
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.
Measured: Up to 3 years
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.
Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Oct 201416 Oct 2020

First posted22 May 2014 (estimated)
Study startOct 2014
Primary completion26 Nov 2018
Study completion16 Oct 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Hematologic MalignanciesStudies of the same condition, open and under way.
More trials run by University of Michigan Rogel Cancer CenterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 53 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02145403
Sponsor's protocol ID: UMCC 2014.010
Other IDs: HUM00084170
Status last verified: Dec 2021
First submitted: 20 May 2014
Last updated: 3 Jan 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 3 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT02145403
Acronym / sponsor ID: UMCC 2014.010
Conditions: Hematologic Malignancies, Relapse, Graft-Versus-Host Disease
Keywords: Allogeneic Transplantation, Carfilzomib, Relapse, Graft-Versus-Host Disease, Multiple Myeloma, Lymphoma, Leukemia
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 53 participants (actual)
Lead sponsor: University of Michigan Rogel Cancer CenterUniversity, hospital or other
Study start: Oct 2014 (actual)
Primary completion: 26 Nov 2018 (actual)
Study completion: 16 Oct 2020 (actual)
First posted: 22 May 2014 (estimated)
Results: Posted 6 Jan 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Carfilzomib	Experimental	Drug: Carfilzomib, Drug: TacrolimusCarfilzomib will be administered IV over 30 minutes, starting at dose level 1 (20 mg/m2 IV) on Day +1, +2, +6 and +7.

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (9 listed)

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)

Key exclusion criteria (18 listed)

Progressive disease
Active central nervous system involvement by malignancy
Non compliance to medications or medical instructions
Lack of appropriate caregivers
Life expectancy <6 months

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
CarfilzomibAlso: Kyprolis®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.	Drug	Carfilzomib
TacrolimusTacrolimus will be administered at 0.03 mg/kg continuous infusion over 24 hours, starting on day -3 as standard graft-versus-host disease prophylaxis.	Drug	Carfilzomib

Primary outcome

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

6 secondary outcomes

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

Results and safety

Results posted to the registry on 6 Jan 2020, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Dose Level 1 - Maximum Dose Carfilzomib 20 mg/m^2	3	3
Dose Level 2 - Maximum Dose Carfilzomib 27 mg/m^2	0	0
Dose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2	0	0
Dose Level 4 - Maximum Dose Carfilzomib 45 mg/m^2	0	0

Primary outcome: Phase I: Maximum Tolerated Dose (MTD) of Carfilzomib

Time frame: Up to day 28. Number. Unit: milligrams per square meter (mg/m^2)

Measure	Phase 1 Study Participants n = 14
Value	36

Population analysed: Phase 1 study participants

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

Time frame: 1 year. Number (95% Confidence Interval). Unit: percentage of participants

Measure	Dose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2 IV n = 39
Value	31 (17 to 46)

Population analysed: Subjects who have received all 4 doses of carfilzomib at the maximum tolerated dose (MTD) level (dose level 3, 36 mg/m\^2): 39 subjects total. Note: three subjects who completed 4 doses of carfilzomib at the MTD during the phase 1 portion of the study were included in phase 2 analysis of the primary outcome measure.

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse event data were collected up to 100 days after the last dose of carfilzomib. All-cause mortality includes all patients followed for up to three years after their first dose of carfilzomib; total duration of data collection was 6 years with an average duration of 1.8 years.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Dose Level 1 - Maximum Dose Carfilzomib 20 mg/m^2 IV	1 of 3 (33.3%)	3 of 3 (100%)	1 of 3
Dose Level 2 - Maximum Dose Carfilzomib 27 mg/m^2 IV	2 of 3 (66.7%)	0 of 3 (0%)	2 of 3
Dose Level 3 - Maximum Dose Carfilzomib 36 mg/m^2 IV	25 of 41 (61%)	16 of 41 (39%)	18 of 41
Dose Level 4 - Maximum Dose Carfilzomib 45 mg/m^2 IV	4 of 4 (100%)	3 of 4 (75%)	2 of 4

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2022.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Attaphol Pawarode, M.D. principal investigator

University of Michgan Cancer Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Carfilzomib and Tacrolimus in people with Hematologic Malignancies and Relapse, run by University of Michigan Rogel Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 6 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I: Maximum Tolerated Dose (MTD) of Carfilzomib (time frame: Up to day 28). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02145403.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jan 2022.