LeukemiaPhase 1AML ALLNCT01137747
Carfilzomib in Patients With Relapsed Acute Myeloid or Acute Lymphoblastic Leukemia
A Phase 1 study testing Carfilzomib in people with Leukemia, run by Washington University School of Medicine at 1 site in United States.
Trial summary
This study is to test escalating doses of carfilzomib in patients with relapsed acute myeloid and acute lymphoblastic leukemia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia
- What is being tested?
- Carfilzomib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2010to Jul 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Disease Related
- Relapsed acute myeloid leukemia or relapsed acute lymphoblastic leukemia. Patients with primary refractory AML or ALL (after standard induction chemotherapy) are also eligible if they have evidence of persistent disease documented by bone marrow biopsy done within 14 days of trial entry.
- Subjects must have disease documented on bone marrow biopsy done within 14 days of starting cycle 1
- Demographic
- Males and females ≥ 18 years old.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
Show all 15Show fewer
- Laboratory
- Peripheral blast count must be ≤ 30,000 on the first day of study drug administration. Leukopheresis and hydrea are acceptable measures of leuko-reduction prior to beginning the study drug.
- Adequate hepatic function with ALT/SGPT ≤ 2.5 x upper limit of normal (ULN) or ≤ 5.0 x ULN if the transaminase elevation is due to leukemic involvement. Serum bilirubin ≤ 2.0 x ULN.
- Adequate renal function with calculated creatinine clearance of ≥ 15 mL/min (calculated using the Cockcroft and Gault formula) or measured creatinine clearance ≥ 15 mL/min from 24 hour urine collection.
- Uric acid, if elevated, must be corrected to within laboratory normal range prior to dosing.
- Ethical / Other
- Ability to provide written informed consent obtained prior to participation in the study and any related procedures being performed.
- Women of childbearing age must have a negative serum pregnancy test within 7 days prior to initiating therapy and be willing to not become pregnant to by using effective contraception while undergoing treatment and for at least 3 months afterwards.
- Men must be willing not to father a new child while receiving therapy. They must use an effective barrier method of contraception during the study and for 3 months following the last dose.
Who cannot join
- Subjects meeting any of the following exclusion criteria are not eligible to enroll in this study.
- Disease Related
- Active CNS leukemia.
- Receiving any other investigational agents within 14 days of first dose of study drug.
- Had cytotoxic chemotherapy within 14 days of first dose of study drug. Leukopheresis and hydrea are allowed as specified per protocol
- Had allogeneic stem cell transplantation within 100 days of first dose of study drug. Patients with a history of graft-versus-host disease on a stable dose of immunosuppression and who are otherwise medically fit are eligible for the trial. Patients with active graft-versus host disease are excluded.
Show all 17Show fewer
- Had radiotherapy within 14 days prior to study enrollment.
- Subjects with pleural effusions requiring thoracentesis or ascites requiring paracentesis.
- Concurrent Conditions
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, congestive heart failure of NYHA class 3 or 4, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements.
- Major surgery within three weeks before Day 1.
- Active hepatitis A, B, C infection.
- Known or suspected HIV infection or subjects who are HIV seropositive.
- Significant neuropathy (Grade 3, 4) at the time of study initiation.
- Patients in whom oral and/or IV fluid hydration is contraindicated, e.g., due to pre-existing pulmonary, cardiac, or renal impairment, will not be eligible to participate in the clinical trial.
- Ethical / Other
- -Female subjects who are pregnant or lactating.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Official title: A Phase I Trial of Carfilzomib in Adult Patients With Relapsed Acute Myeloid and Acute Lymphoblastic Leukemia
This study is to test escalating doses of carfilzomib in patients with relapsed acute myeloid and acute lymphoblastic leukemia.
Read the detailed description
Several published studies have demonstrated the in vitro anti-leukemic activity of carfilzomib in leukemia cell lines as well as in primary human acute myeloid and acute lymphoblastic leukemia cells. The anti-leukemic activity of carfilzomib was consistently more potent than that of bortezomib, particularly at doses ≥27mg/m2. Importantly, patients treated on the phase I and phase II carfilzomib trials have had low rates of treatment-associated neuropathy. Several large collaborative groups have current phase II clinical trials that incorporate bortezomib into the treatment regimens for acute myeloid or acute lymphoblastic leukemia. Thus, there is a strong rationale for a study of carfilzomib, a potentially more potent proteasome inhibitor with less toxicity, in patients with relapsed acute leukemias.
- Conditions
- Leukemia
- Being tested
- Carfilzomib
- Keywords
- carfilzomib, acute myeloid leukemia, acute lymphoblastic leukemia, phase I
- Medical subject headings
- Leukemia, Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarfilzomibDrug
Also called Kyprolis
| Study group | Role | What they receive |
|---|---|---|
| Dose Level 0 (starting dose) | Experimental | Carfilzomib - 20 mg/m2 days 1 and 2, 27 mg/m2 for days 8 and 9 of cycle 1 only and, if days 8 and 9 are tolerated, may be increased to 36 mg/m2 for all subsequent doses. If DLT occurs while receiving 36 mg/m2, the dose may be reduced to 27 mg/m2.
Dosing schedule is days 1, 2, 8, 9, 15, 16, 22, and 23 with no rest period during the 28 day cycle. Dose will be given IV over 30 minutes.
2 cycles of treatment will be given. If the patient enters at leat a partial remission, then treatment may be extended up to 4 additional cycles. Receives: Drug: Carfilzomib |
| Dose Level +1 | Experimental | Carfilzomib - 20 mg/m2 days 1 and 2, 36 mg/m2 for days 8 and 9 of cycle 1 only and, if days 8 and 9 are tolerated, may be increased to 45 mg/m2 for all subsequent doses. If DLT occurs while receiving 45 mg/m2, the dose may be reduced to 36 mg/m2.
Dosing schedule is days 1, 2, 8, 9, 15, 16, 22, and 23 with no rest period during the 28 day cycle. Dose will be given IV over 30 minutes.
2 cycles of treatment will be given. If the patient enters at leat a partial remission, then treatment may be extended up to 4 additional cycles. Receives: Drug: Carfilzomib |
| Dose Level +2 | Experimental | Carfilzomib - 20 mg/m2 days 1 and 2, 45 mg/m2 for days 8 and 9 of cycle 1 only and, if days 8 and 9 are tolerated, may be increased to 56 mg/m2 for all subsequent doses. If DLT occurs while receiving 56 mg/m2, the dose may be reduced to 45 mg/m2.
Dosing schedule is days 1, 2, 8, 9, 15, 16, 22, and 23 with no rest period during the 28 day cycle. Dose will be given IV over 30 minutes.
2 cycles of treatment will be given. If the patient enters at leat a partial remission, then treatment may be extended up to 4 additional cycles. Receives: Drug: Carfilzomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT)
A hematologic adverse event will not be considered a dose-limiting toxicity. Tumor lysis syndrome is not a dose-limiting toxicity.
Measured: End of cycle 1
Secondary outcomes (5)
To determine the rate of morphologic complete remission (CR)
Measured: Every 2 months for 2 years after first dose of study drug
To determine the rates of cytogenetic complete remission (CRc) morphologic complete remission with incomplete count recovery (CRi), overall response rate (CR+ CRi), partial remission (PR), stable disease and hematologic improvement.
Measured: Every 2 months for 2 years after first dose of study drug
To determine the time to response, remission duration, progression-free survival, event-free survival and overall survival of patients treated with carfilzomib.
Measured: Every 2 months for 2 years after first dose of study drug
To determine the safety and tolerability of carfilzomib by evaluating the number of participants with adverse events as a measure of safety and tolerability.
Measured: 30 days after end of treatment
To prospectively collect serum and bone marrow specimens to determine biomarkers of response and correlative ex vivo studies of the anti-leukemic activity of carfilzomib.
Measured: Baseline, Day 28 of cycles 1, 2, 4, 6 & End of Study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2010 (estimated)
- Study startOct 2010
- Primary completionAug 2014
- Study completionJul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Ravi Vij, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01137747
- Sponsor's protocol ID
- 10-0913 / 201107117
- Acronym
- AML ALL
- Status last verified
- Jun 2016
- First submitted
- 2 Jun 2010
- Last updated
- 14 Jun 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Carfilzomib in Adult Patients With Relapsed Acute Myeloid and Acute Lymphoblastic Leukemia
- ClinicalTrials.gov ID
- NCT01137747
- Acronym / sponsor ID
- AML ALL / 10-0913 / 201107117
- Conditions
- Leukemia
- Keywords
- carfilzomib, acute myeloid leukemia, acute lymphoblastic leukemia, phase I
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- Oct 2010
- Primary completion
- Aug 2014 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 4 Jun 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is to test escalating doses of carfilzomib in patients with relapsed acute myeloid and acute lymphoblastic leukemia.
Detailed description
Several published studies have demonstrated the in vitro anti-leukemic activity of carfilzomib in leukemia cell lines as well as in primary human acute myeloid and acute lymphoblastic leukemia cells. The anti-leukemic activity of carfilzomib was consistently more potent than that of bortezomib, particularly at doses ≥27mg/m2. Importantly, patients treated on the phase I and phase II carfilzomib trials have had low rates of treatment-associated neuropathy. Several large collaborative groups have current phase II clinical trials that incorporate bortezomib into the treatment regimens for acute myeloid or acute lymphoblastic leukemia. Thus, there is a strong rationale for a study of carfilzomib, a potentially more potent proteasome inhibitor with less toxicity, in patients with relapsed acute leukemias.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose Level 0 (starting dose) | Experimental | Drug: CarfilzomibCarfilzomib - 20 mg/m2 days 1 and 2, 27 mg/m2 for days 8 and 9 of cycle 1 only and, if days 8 and 9 are tolerated, may be increased to 36 mg/m2 for all subsequent doses. If DLT occurs while receiving 36 mg/m2, the dose may be reduced to 27 mg/m2. Dosing schedule is days 1, 2, 8, 9, 15, 16, 22, and 23 with no rest period during the 28 day cycle. Dose will be given IV over 30 minutes. 2 cycles of treatment will be given. If the patient enters at leat a partial remission, then treatment may be extended up to 4 additional cycles. |
| Dose Level +1 | Experimental | Drug: CarfilzomibCarfilzomib - 20 mg/m2 days 1 and 2, 36 mg/m2 for days 8 and 9 of cycle 1 only and, if days 8 and 9 are tolerated, may be increased to 45 mg/m2 for all subsequent doses. If DLT occurs while receiving 45 mg/m2, the dose may be reduced to 36 mg/m2. Dosing schedule is days 1, 2, 8, 9, 15, 16, 22, and 23 with no rest period during the 28 day cycle. Dose will be given IV over 30 minutes. 2 cycles of treatment will be given. If the patient enters at leat a partial remission, then treatment may be extended up to 4 additional cycles. |
| Dose Level +2 | Experimental | Drug: CarfilzomibCarfilzomib - 20 mg/m2 days 1 and 2, 45 mg/m2 for days 8 and 9 of cycle 1 only and, if days 8 and 9 are tolerated, may be increased to 56 mg/m2 for all subsequent doses. If DLT occurs while receiving 56 mg/m2, the dose may be reduced to 45 mg/m2. Dosing schedule is days 1, 2, 8, 9, 15, 16, 22, and 23 with no rest period during the 28 day cycle. Dose will be given IV over 30 minutes. 2 cycles of treatment will be given. If the patient enters at leat a partial remission, then treatment may be extended up to 4 additional cycles. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Disease Related
- Relapsed acute myeloid leukemia or relapsed acute lymphoblastic leukemia. Patients with primary refractory AML or ALL (after standard induction chemotherapy) are also eligible if they have evidence of persistent disease documented by bone marrow biopsy done within 14 days of trial entry.
- Subjects must have disease documented on bone marrow biopsy done within 14 days of starting cycle 1
- Demographic
- Males and females ≥ 18 years old.
Key exclusion criteria (17 listed)
- Subjects meeting any of the following exclusion criteria are not eligible to enroll in this study.
- Disease Related
- Active CNS leukemia.
- Receiving any other investigational agents within 14 days of first dose of study drug.
- Had cytotoxic chemotherapy within 14 days of first dose of study drug. Leukopheresis and hydrea are allowed as specified per protocol
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 | Drug | Dose Level +1, Dose Level +2, Dose Level 0 (starting dose) |
Primary outcome
To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT)
Time frame: End of cycle 1
A hematologic adverse event will not be considered a dose-limiting toxicity. Tumor lysis syndrome is not a dose-limiting toxicity.
5 secondary outcomes
To determine the rate of morphologic complete remission (CR)
Time frame: Every 2 months for 2 years after first dose of study drug
To determine the rates of cytogenetic complete remission (CRc) morphologic complete remission with incomplete count recovery (CRi), overall response rate (CR+ CRi), partial remission (PR), stable disease and hematologic improvement.
Time frame: Every 2 months for 2 years after first dose of study drug
To determine the time to response, remission duration, progression-free survival, event-free survival and overall survival of patients treated with carfilzomib.
Time frame: Every 2 months for 2 years after first dose of study drug
To determine the safety and tolerability of carfilzomib by evaluating the number of participants with adverse events as a measure of safety and tolerability.
Time frame: 30 days after end of treatment
To prospectively collect serum and bone marrow specimens to determine biomarkers of response and correlative ex vivo studies of the anti-leukemic activity of carfilzomib.
Time frame: Baseline, Day 28 of cycles 1, 2, 4, 6 & End of Study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2016.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
Related trials for Leukemia
RecruitingPhase 2
Tafasitamab With Acalabrutinib and Venetoclax for the Treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Chronic Lymphocytic Leukemia, Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Enrolling by invitationObservational study
Natural History Study of Early Life Exposures in Agriculture (ELEA)
Prostate Cancer, Leukemia
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 1
Vididencel in CML-CP Patients With MRD
CML (Chronic Myelogenous Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
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.
Ravi Vij, M.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Carfilzomib in people with Leukemia, run by Washington University School of Medicine 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 15 inclusion and 17 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 14 Jun 2016. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) (time frame: End of cycle 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 14 Jun 2016.