Acute Lymphoblastic Leukemia in Complete RemissionPhase 1NCT02578511
Standard Maintenance POMP/D Plus Ixazomib Maintenance Therapy in Adult Patients With Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma or Mixed Phenotype Acute Leukemia in Complete Remission (CR)
A Phase 1 study testing Ixazomib in people with Acute Lymphoblastic Leukemia in Complete Remission and Lymphoblastic Lymphoma in Complete Remission, run by Ehab L Atallah at 1 site in United States.
Trial summary
In this phase I study, escalating doses of IXAZOMIB will be combined with the POMP/D regimen. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Lymphoblastic Leukemia in Complete Remission, Lymphoblastic Lymphoma in Complete Remission, Mixed Phenotype Acute Leukemia in Complete Remission
- What is being tested?
- Ixazomib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Jun 2017to 13 Feb 2018
- 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
- Male or female patients 18 years or older.
- Have B-precursor, T cell ALL, MPAL or LBL in CR following therapy and receiving maintenance therapy. Patients with persistent minimal residual disease and/or in complete remission with incomplete platelet recovery are not eligible.
- Prior therapy: Should have achieved CR following the induction and intensification phases of treatment, with no limit on the number of prior treatment regimens, and started treatment with POMP/D maintenance. Patients who achieved CRp or CR with persistence of minimal residual disease are not eligible.
- Patients are eligible after allogeneic stem cell transplantation.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
- Patients must meet the following clinical laboratory criteria:
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- Total bilirubin < 1.5 X the upper limit of the normal range (ULN).
- Alanine aminotransferase (ALT) and aspartate aminotransferase. (AST) < 3 X ULN.
- Calculated creatinine clearance > 30 mL/min.
- Absolute neutrophil count (ANC) > 1,000/cmm and platelets > 75,000/cmm.
- Patient has a life expectancy of at least six months.
- Patients must be at least two weeks from major surgery, radiation therapy, participation in other investigational trials and have recovered from clinically significant toxicities of these prior treatments.
- Patients should be on stable doses of 6-mercaptopurine, methotrexate, vincristine and prednisone/dexamethasone as part of the POMP/D regimen, for a minimum of eight weeks PRIOR to starting ixazomib treatment.
- Patients should have at least six months of therapy with the POMP/D regimen remaining prior to starting IXAZOMIB (MLN9708).
- Female patients who:
- Are postmenopausal for at least one year before the screening visit, OR
- Are surgically sterile, OR
- If they are of childbearing potential, agree to practice two effective. methods of contraception, at the same time, from the time of signing the informed consent form through 90 days after the last dose of study drug, AND
- Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)
- Male patients, even if surgically sterilized (i.e., status postvasectomy), must agree to one of the following:
- Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR
- Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
- Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods] and withdrawal are not acceptable methods of contraception.)
Who cannot join
- Systemic treatment, within 14 days before study enrollment, with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of ginkgo biloba or St. John's wort.
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, or psychiatric illness/social situations that would limit compliance with study requirements. Patients should not have evidence of active infection.
- Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements, or GI procedure that could interfere with the oral absorption or tolerance of treatment.
- Active chronic graft vs. host disease requiring therapy.
- Patient has ≥ grade 2 peripheral neuropathy.
- Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the trial start and throughout the duration of this trial.
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- Failure to have fully recovered (i.e., < grade 1 toxicity) from the reversible effects of prior chemotherapy.
- Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past six months.
- Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with treatment completion according to this protocol.
- Known allergy to any of the study medications, their analogues or excipients in the various formulations of any agent.
- Diagnosed or treated for another malignancy within two years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
- Female patients who are breastfeeding or have a positive serum pregnancy test during the screening.
Trial locations and contacts
1 site in 1 country.
United States1 site
Froedtert & the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
About this study
Official title: Standard Maintenance [POMP/D (Methotrexate, 6 - Mercaptopurine, Vincristine, Prednisone/Dexamethasone)] Plus Ixazomib Maintenance Therapy in Adults With Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma or Mixed Phenotype Acute Leukemia in Complete Remission (CR)
In this phase I study, escalating doses of IXAZOMIB will be combined with the POMP/D regimen.
Read the detailed description
PRIMARY OBJECTIVE
The primary objective is to determine the maximum-tolerated dose of IXAZOMIB (MLN9708) (maximum of 4 mg, which is the recommended phase II dose for IXAZOMIB (MLN9708) in combination with standard maintenance therapy with POMP/D (methotrexate, 6- mercaptopurine, vincristine, prednisone/dexamethasone) and to assess the tolerability of POMP/D and IXAZOMIB (MLN9708) maintenance in adult patients with acute lymphoblastic leukemia, lymphoblastic lymphoma (LBL) or mixed phenotype acute leukemia (MPAL) in complete remission (CR).
SECONDARY OBJECTIVE
To determine the three-year progression-free survival (PFS) of patients treated with oral IXAZOMIB (MLN9708) and standard maintenance regimen. Progression-free survival will be measured from the start of induction to disease relapse.
STUDY DESIGN
The maximum-tolerated dose of single agent IXAZOMIB was 1.76 to 2.0mg/m2 when given on a twice a week schedule1 and > 2.34 mg/m2 to 2.97 mg/m2 on a weekly schedule in previous studies.
Three patients will be treated per dose level unless dose-limiting toxicity (DLT) is observed. The starting dose of IXAZOMIB will be 3 mg orally on days 1, 8 and 15. If no DLT is seen in the first three patients, the dose will be increased to 4 mg on days 1, 8 and 15 in a classic 3 +3 phase I design. We will not attempt to increase the dose beyond 4 mg orally which, if achieved with acceptable toxicity, would be accepted as the recommended phase 2 dose (RP2D). Zero of three DLTs would allow escalation to the next dose level. One of three DLTs will require expanding to six patients; one of six DLTs will allow escalation again. Two DLTs will require dose de-escalation. The maximum-tolerated dose (MTD) will be the highest dose administered at which no more than one DLT was observed.
- Conditions
- Acute Lymphoblastic Leukemia in Complete Remission, Lymphoblastic Lymphoma in Complete Remission, Mixed Phenotype Acute Leukemia in Complete Remission
- Being tested
- Ixazomib
- Keywords
- Acute Lymphoblastic Leukemia in Complete Remission, Lymphoblastic Lymphoma in Complete Remission, Mixed Phenotype Acute Leukemia in Complete Remission, IXAZOMIB, POMP/D, Phase I, Early Phase, Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma, Mixed Phenotype Acute Leukemia, ALL
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Biphenotypic, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IxazomibDrug
Patients who have been on stable doses of 6 - MP, vincristine, and methotrexate for a minimum of eight weeks and have at least six months remaining of maintenance are eligible to receive Ixazomib, which will be administered on days 1, 8 and 15.
| Study group | Role | What they receive |
|---|---|---|
| Ixazomib (MLN9708) in combination with standard POMP/D | Experimental | Patients who are receiving maintenance therapy with the POMP/D (Methotrexate, 6-Mercaptopurine, Vincristine, Prednisone/Dexamethasone) will be enrolled. Each cycle will be 28 days. The patients will receive IV vincristine, dexamethasone or prednisone, methotrexate and 6 - Mercaptopurine. Ixazomib will be administered on days 1, 8 and 15.
Both prednisone and dexamethasone are acceptable drugs in maintenance therapy. For example, in the HyperCVAD regimen or the CALGB 8811 prednisone is used. Patients will continue the same maintenance regimen they are receiving and ixazomib will be added to that. Receives: Drug: Ixazomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose of ixazomib with POMP/D maintenance
The patient cohort enrolled at each dose level will be monitored for dose-limiting toxicity for eight weeks prior to enrolling the next cohort of patients at a new dose level. Subsequent patient cohorts will be enrolled at doses according to the CRM design. A maximum sample size of 12 patients will be enrolled over four potential doses to determine the maximum tolerated dose of ixazomib with POMP/D maintenance. Adverse events will be summarized with descriptive statistics at each dose level of ixazomib.
Measured: Eight (8) weeks
Secondary outcomes (1)
Progression-free survival of patients treated with oral Ixazomib and standard maintenance regimen.
Progression-free survival will be measured from the time of diagnosis to disease relapse.
Measured: Three (3) years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2015 (estimated)
- Study start29 Jun 2017
- Primary completion13 Feb 2018
- Study completion13 Feb 2018
Why it stopped: No enrollment, another competing study and difficult to find the right person to enroll on this study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic Leukemia in Complete RemissionStudies of the same condition, open and under way.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ehab L Atallah
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Ehab L Atallah, Medical College of Wisconsin
- Investigators
- Ehab Atallah, MD, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02578511
- Sponsor's protocol ID
- PRO25835
- Status last verified
- Feb 2018
- First submitted
- 30 Sep 2015
- Last updated
- 15 Feb 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Standard Maintenance [POMP/D (Methotrexate, 6 - Mercaptopurine, Vincristine, Prednisone/Dexamethasone)] Plus Ixazomib Maintenance Therapy in Adults With Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma or Mixed Phenotype Acute Leukemia in Complete Remission (CR)
- ClinicalTrials.gov ID
- NCT02578511
- Acronym / sponsor ID
- PRO25835
- Conditions
- Acute Lymphoblastic Leukemia in Complete Remission, Lymphoblastic Lymphoma in Complete Remission, Mixed Phenotype Acute Leukemia in Complete Remission
- Keywords
- Acute Lymphoblastic Leukemia in Complete Remission, Lymphoblastic Lymphoma in Complete Remission, Mixed Phenotype Acute Leukemia in Complete Remission, IXAZOMIB, POMP/D, Phase I, Early Phase, Acute Lymphoblastic Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No enrollment, another competing study and difficult to find the right person to enroll on this study.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Ehab L AtallahUniversity, hospital or other
- Study start
- 29 Jun 2017 (actual)
- Primary completion
- 13 Feb 2018 (actual)
- Study completion
- 13 Feb 2018 (actual)
- First posted
- 19 Oct 2015 (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.
In this phase I study, escalating doses of IXAZOMIB will be combined with the POMP/D regimen.
Detailed description
PRIMARY OBJECTIVE
The primary objective is to determine the maximum-tolerated dose of IXAZOMIB (MLN9708) (maximum of 4 mg, which is the recommended phase II dose for IXAZOMIB (MLN9708) in combination with standard maintenance therapy with POMP/D (methotrexate, 6- mercaptopurine, vincristine, prednisone/dexamethasone) and to assess the tolerability of POMP/D and IXAZOMIB (MLN9708) maintenance in adult patients with acute lymphoblastic leukemia, lymphoblastic lymphoma (LBL) or mixed phenotype acute leukemia (MPAL) in complete remission (CR).
SECONDARY OBJECTIVE
To determine the three-year progression-free survival (PFS) of patients treated with oral IXAZOMIB (MLN9708) and standard maintenance regimen. Progression-free survival will be measured from the start of induction to disease relapse.
STUDY DESIGN
The maximum-tolerated dose of single agent IXAZOMIB was 1.76 to 2.0mg/m2 when given on a twice a week schedule1 and > 2.34 mg/m2 to 2.97 mg/m2 on a weekly schedule in previous studies.
Three patients will be treated per dose level unless dose-limiting toxicity (DLT) is observed. The starting dose of IXAZOMIB will be 3 mg orally on days 1, 8 and 15. If no DLT is seen in the first three patients, the dose will be increased to 4 mg on days 1, 8 and 15 in a classic 3 +3 phase I design. We will not attempt to increase the dose beyond 4 mg orally which, if achieved with acceptable toxicity, would be accepted as the recommended phase 2 dose (RP2D). Zero of three DLTs would allow escalation to the next dose level. One of three DLTs will require expanding to six patients; one of six DLTs will allow escalation again. Two DLTs will require dose de-escalation. The maximum-tolerated dose (MTD) will be the highest dose administered at which no more than one DLT was observed.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ixazomib (MLN9708) in combination with standard POMP/D | Experimental | Drug: IxazomibPatients who are receiving maintenance therapy with the POMP/D (Methotrexate, 6-Mercaptopurine, Vincristine, Prednisone/Dexamethasone) will be enrolled. Each cycle will be 28 days. The patients will receive IV vincristine, dexamethasone or prednisone, methotrexate and 6 - Mercaptopurine. Ixazomib will be administered on days 1, 8 and 15. Both prednisone and dexamethasone are acceptable drugs in maintenance therapy. For example, in the HyperCVAD regimen or the CALGB 8811 prednisone is used. Patients will continue the same maintenance regimen they are receiving and ixazomib will be added to that. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- Male or female patients 18 years or older.
- Have B-precursor, T cell ALL, MPAL or LBL in CR following therapy and receiving maintenance therapy. Patients with persistent minimal residual disease and/or in complete remission with incomplete platelet recovery are not eligible.
- Prior therapy: Should have achieved CR following the induction and intensification phases of treatment, with no limit on the number of prior treatment regimens, and started treatment with POMP/D maintenance. Patients who achieved CRp or CR with persistence of minimal residual disease are not eligible.
- Patients are eligible after allogeneic stem cell transplantation.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
Key exclusion criteria (12 listed)
- Systemic treatment, within 14 days before study enrollment, with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of ginkgo biloba or St. John's wort.
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, or psychiatric illness/social situations that would limit compliance with study requirements. Patients should not have evidence of active infection.
- Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements, or GI procedure that could interfere with the oral absorption or tolerance of treatment.
- Active chronic graft vs. host disease requiring therapy.
- Patient has ≥ grade 2 peripheral neuropathy.
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 |
|---|---|---|
| IxazomibPatients who have been on stable doses of 6 - MP, vincristine, and methotrexate for a minimum of eight weeks and have at least six months remaining of maintenance are eligible to receive Ixazomib, which will be administered on days 1, 8 and 15. | Drug | Ixazomib (MLN9708) in combination with standard POMP/D |
Primary outcome
Maximum tolerated dose of ixazomib with POMP/D maintenance
Time frame: Eight (8) weeks
The patient cohort enrolled at each dose level will be monitored for dose-limiting toxicity for eight weeks prior to enrolling the next cohort of patients at a new dose level. Subsequent patient cohorts will be enrolled at doses according to the CRM design. A maximum sample size of 12 patients will be enrolled over four potential doses to determine the maximum tolerated dose of ixazomib with POMP/D maintenance. Adverse events will be summarized with descriptive statistics at each dose level of ixazomib.
1 secondary outcome
Progression-free survival of patients treated with oral Ixazomib and standard maintenance regimen.
Time frame: Three (3) years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Feb 2018.
- Individual participant dataSharing planned: Undecided
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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.
Ehab Atallah, MD principal investigator
Medical College of Wisconsin
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 Ixazomib in people with Acute Lymphoblastic Leukemia in Complete Remission and Lymphoblastic Lymphoma in Complete Remission, run by Ehab L Atallah 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 24 inclusion and 12 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: withdrawn, as of the sponsor's last update on 15 Feb 2018. 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 was withdrawn before enrolling participants, so there are no results.
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?
Maximum tolerated dose of ixazomib with POMP/D maintenance (time frame: Eight (8) weeks). 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 15 Feb 2018.