Relapsed or Refractory Acute Lymphoblastic LeukemiaPhase 1NCT01887587

Vincristine, Doxorubicin, And Dexamethasone + Ixazomib in Acute Lymphoblastic Leukemia (ALL), Lymphoblastic Lymphoma Or Mixed Phenotype Acute Leukemia

A Phase 1 study testing MLN9708, Vincristine and Doxorubicin in people with Relapsed or Refractory Acute Lymphoblastic Leukemia and Relapsed or Refractory Lymphoblastic Lymphoma, run by Ehab L Atallah at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This is a phase I study of vincristine, doxorubicin and dexamethasone (modified VXD) plus MLN9708 in adults with relapsed or refractory acute lymphoblastic leukemia/lymphoma, lymphoblastic lymphoma or mixed phenotype acute leukemia. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Relapsed or Refractory Acute Lymphoblastic Leukemia, Relapsed or Refractory Lymphoblastic Lymphoma, Mixed Phenotype Acute Leukemia
What is being tested?: MLN9708, Vincristine and Doxorubicin
Type of treatment: Pill or oral medicine, Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 5 participants
Where: 1 siteUnited States
Study dates: Jun 2013to 29 Feb 2016
Phase: Phase 1
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 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 relapsed B or T-precursor acute lymphocytic leukemia/lymphoma, lymphoblastic lymphoma or mixed phenotype acute leukemia with increased bone marrow or peripheral blood blasts by morphology with or without CNS involvement
Prior therapy: At least two prior treatment attempts to induce remission with no limit on the number of prior treatment regimens.
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 unless the cytopenias are secondary to disease
Life expectancy reasonably adequate for evaluating the treatment effect
Patients must be at least 2 weeks from major surgery, radiation therapy, participation in other investigational trials and have recovered from clinically significant toxicities of these prior treatments
Female patients who:
Are postmenopausal for at least 1 year before the screening visit, OR
Are surgically sterile, OR
If they are of childbearing potential, agree to practice 2 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, OR
Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
Male patients, even if surgically sterilized (ie, status post-vasectomy), 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
Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the subject. (Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.).

Who cannot join

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:
Patients who are Ph+ ALL who are naive to therapy with an approved tyrosine kinase inhibitor.
Prior exposure to ≥350 mg/m2 of anthracycline (in doxorubicin equivalent dosing), or left ventricular fractional shortening less than 50%.
Failure to have fully recovered (ie, ≤ Grade 2 toxicity) from the effects of prior chemotherapy regardless of the interval since last treatment.
Major surgery within 14 days before enrollment.
Chemotherapy in the last 14 days. (Steroids or Intrathecal chemotherapy will be allowed).

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Systemic treatment, within 7 days before study enrollment, with strong inhibitors of cytochrome P450 1A2 (CYP1A2) (e.g., fluvoxamine, enoxacin, ciprofloxacin), strong inhibitors of cytochrome P4503A (CYP3A) (e.g., clarithromycin, telithromycin, itraconazole, voriconazole, ketoconazole, nefazodone, posaconazole) or 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 receiving intravenous antibiotics for infections that are under control may be included in this study.
Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
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.
Diagnosed or treated for another malignancy within 2 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.
Patient has ≥ Grade 2 peripheral neuropathy.
Participation in clinical trials with other investigational agents not included in this trial, within 14 days of the start of this trial and throughout the duration of this trial.
Female patients who are breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug.

Trial locations and contacts

1 site in 1 country.

United States1 site

Froedtert Hospital and the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226

Other trials in United States

About this study

Official title: Phase I Study Of Vincristine, Doxorubicin, And Dexamethasone (VXD) Plus Ixazomib In Adults With Relapsed Or Refractory Acute Lymphoblastic Leukemia/Lymphoma, Lymphoblastic Lymphoma Or Mixed Phenotype Acute Leukemia

Read the detailed description

In this phase I study, escalating doses of MLN9708 will be combined with a fixed dose modified VXD regimen. The study drug, MLN9708, will be administered on day 1, 8, and 15. If the patient experiences a dose limiting toxicity (DLT) the dose of MLN9708 maybe reduced to the next dose level on day 8 or day 15 in that patient. DLT would be any grade 3 or more toxicity which is thought to be probably or definitely related to MLN9708. Three patients will be treated per dose level unless DLT is observed. The starting dose of MLN9708 will be 2.3 mg orally on days 1, 8 and 15. If toxicity is seen at this level then dose may be reduced to 1.5 mg (dose level -1) . If no DLT is seen in the first 3 patients, the dose will be increased to 3 mg and then to 4 mg orally 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). 0 of 3 DLTs would allow escalation to the next dose level. 1 of 3 DLTs will require expanding to six patients; 1 of 6 DLTs will allow escalation again. 2 DLTs will require dose de-escalation. The maximum tolerated dose (MTD) will be the highest dose administered at which no more than 1 DLT was observed. All patients will be evaluated for hematopoetic stem cell transplantation. If patients achieve complete response (CR) and are eligible for hematopoietic stem cell transplantation (HSCT), they will proceed to HSCT. If they are not eligible, no donor is identified or if HSCT will be delayed, and the patient has achieved benefit, then treatment maybe repeated at the discretion of the investigator. A total of 9-18 patients will be enrolled on the study. The study duration would be about 2 years.

Conditions: Relapsed or Refractory Acute Lymphoblastic Leukemia, Relapsed or Refractory Lymphoblastic Lymphoma, Mixed Phenotype Acute Leukemia
Being tested: MLN9708, Vincristine, Doxorubicin, Dexamethasone
Medical subject headings: Recurrence, 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.

MLN9708Drug
Also called Ixazomib
VincristineDrug
Also called Oncovin
DoxorubicinDrug
Also called Doxil, hydroxydaunorubicin
DexamethasoneDrug
Also called Decadron, Dexasone, Solurex, Baycadron

Study groups in NCT01887587
Study group	Role	What they receive
(modified VXLD) plus MLN9708	Experimental	Vincristine-1.5 mg/m2 to a max dose of 2 mg IV on days 1, 8, 15 and 22 Dexamethasone- 10 mg/m2 orally or IV on days 1-14 Doxorubicin- 60 mg/m2 on day 1 by IV bolus. MLN9708 (Ixazomib)- 2.3 mg orally on days 1, 8 and 15. Escalations will be to 3mg or 4 mg, respectively, on days 1, 8 and 15 based on the dosing schema. For patients without central nervous system (CNS) involvement: * Cytarabine 100 mg administered intrathecally on day 1 (cytarabine dose should be reduced to 50 mg if given through a central ommaya reservoir) * Methotrexate 12 mg administered intrathecally on day 8 For patients with CNS involvement: -Cytarabine 100 mg administered intrathecally on day 1 (+/-1 day) (cytarabine dose should be reduced to 50 mg if given through a central ommaya reservoir) Triple intrathecal chemotherapy with cytarabine 30 mg, methotrexate 15 mg and hydrocortisone 15 mg on (Day 1, 8, 15 and 22 (+/-1 day)). Receives: Drug: MLN9708; Drug: Vincristine; Drug: Doxorubicin; Drug: Dexamethasone

What is being measured

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

Adverse Events.
Safety, tolerability will be assessed by counting the number of participants experiencing adverse events at 8 weeks post treatment.
Measured: Baseline to 30 days post treatment; approximately 8 weeks
Optimal Dose of MLN9708
This measure will be the maximum tolerated dose (MTD) at which no more than 1 Dose Limiting Toxicity (DLT) is observed. The starting dose of MLN9708 will be 2.3 mg orally on days 1, 8 and 15. If no DLT is seen in the first 3 patients, the dose will be increased to 3 mg and then to 4 mg orally 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). 0 of 3 DLTs would allow escalation to the next dose level. 1 of 3 DLTs will require expanding to six patients; 1 of 6 DLTs will allow escalation again. 2 DLTs will require dose de-escalation.
Measured: 8 Weeks

Timeline

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

Jun 201329 Feb 2016

First posted27 Jun 2013 (estimated)
Study startJun 2013
Primary completion29 Feb 2016
Study completion29 Feb 2016

Why it stopped: SAE- risk of overall protocol treatment outweighs benefits

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 Relapsed or Refractory Acute Lymphoblastic LeukemiaStudies 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: 5 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01887587
Sponsor's protocol ID: PRO00020384
Status last verified: Dec 2019
First submitted: 5 Jun 2013
Last updated: 22 Jan 2020
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
Individual data sharing: No

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 22 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I Study Of Vincristine, Doxorubicin, And Dexamethasone (VXD) Plus Ixazomib In Adults With Relapsed Or Refractory Acute Lymphoblastic Leukemia/Lymphoma, Lymphoblastic Lymphoma Or Mixed Phenotype Acute Leukemia
ClinicalTrials.gov ID: NCT01887587
Acronym / sponsor ID: PRO00020384
Conditions: Relapsed or Refractory Acute Lymphoblastic Leukemia, Relapsed or Refractory Lymphoblastic Lymphoma, Mixed Phenotype Acute Leukemia
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: SAE- risk of overall protocol treatment outweighs benefits
Enrolment: 5 participants (actual)
Lead sponsor: Ehab L AtallahUniversity, hospital or other
Study start: Jun 2013
Primary completion: 29 Feb 2016 (actual)
Study completion: 29 Feb 2016 (actual)
First posted: 27 Jun 2013 (estimated)
Results: Posted 22 Jan 2020

Clinical summary

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

Detailed description

Study design

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

Arm	Type	Receives
(modified VXLD) plus MLN9708	Experimental	Drug: MLN9708, Drug: Vincristine, Drug: Doxorubicin, Drug: DexamethasoneVincristine-1.5 mg/m2 to a max dose of 2 mg IV on days 1, 8, 15 and 22 Dexamethasone- 10 mg/m2 orally or IV on days 1-14 Doxorubicin- 60 mg/m2 on day 1 by IV bolus. MLN9708 (Ixazomib)- 2.3 mg orally on days 1, 8 and 15. Escalations will be to 3mg or 4 mg, respectively, on days 1, 8 and 15 based on the dosing schema. For patients without central nervous system (CNS) involvement: * Cytarabine 100 mg administered intrathecally on day 1 (cytarabine dose should be reduced to 50 mg if given through a central ommaya reservoir) * Methotrexate 12 mg administered intrathecally on day 8 For patients with CNS involvement: -Cytarabine 100 mg administered intrathecally on day 1 (+/-1 day) (cytarabine dose should be reduced to 50 mg if given through a central ommaya reservoir) Triple intrathecal chemotherapy with cytarabine 30 mg, methotrexate 15 mg and hydrocortisone 15 mg on (Day 1, 8, 15 and 22 (+/-1 day)).

Who may qualify

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

Key inclusion criteria (20 listed)

Male or female patients 18 years or older
Have relapsed B or T-precursor acute lymphocytic leukemia/lymphoma, lymphoblastic lymphoma or mixed phenotype acute leukemia with increased bone marrow or peripheral blood blasts by morphology with or without CNS involvement
Prior therapy: At least two prior treatment attempts to induce remission with no limit on the number of prior treatment regimens.
Patients are eligible after allogeneic stem cell transplantation
Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Key exclusion criteria (14 listed)

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:
Patients who are Ph+ ALL who are naive to therapy with an approved tyrosine kinase inhibitor.
Prior exposure to ≥350 mg/m2 of anthracycline (in doxorubicin equivalent dosing), or left ventricular fractional shortening less than 50%.
Failure to have fully recovered (ie, ≤ Grade 2 toxicity) from the effects of prior chemotherapy regardless of the interval since last treatment.
Major surgery within 14 days before enrollment.

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
MLN9708Also: Ixazomib	Drug	(modified VXLD) plus MLN9708
VincristineAlso: Oncovin	Drug	(modified VXLD) plus MLN9708
DoxorubicinAlso: Doxil, hydroxydaunorubicin	Drug	(modified VXLD) plus MLN9708
DexamethasoneAlso: Decadron, Dexasone, Solurex, Baycadron	Drug	(modified VXLD) plus MLN9708

Primary outcome

Adverse Events.
Time frame: Baseline to 30 days post treatment; approximately 8 weeks
Safety, tolerability will be assessed by counting the number of participants experiencing adverse events at 8 weeks post treatment.
Optimal Dose of MLN9708
Time frame: 8 Weeks
This measure will be the maximum tolerated dose (MTD) at which no more than 1 Dose Limiting Toxicity (DLT) is observed. The starting dose of MLN9708 will be 2.3 mg orally on days 1, 8 and 15. If no DLT is seen in the first 3 patients, the dose will be increased to 3 mg and then to 4 mg orally 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). 0 of 3 DLTs would allow escalation to the next dose level. 1 of 3 DLTs will require expanding to six patients; 1 of 6 DLTs will allow escalation again. 2 DLTs will require dose de-escalation.

Results and safety

Results posted to the registry on 22 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
(Modified VXLD) Plus MLN9708	5	5

Primary outcome: Adverse Events.

Time frame: Baseline to 30 days post treatment; approximately 8 weeks. Number. Unit: participants

Measure	(Modified VXLD) Plus MLN9708 n = 5
Value	5

Population analysed: At dose level one, 3 patients who were enrolled. The protocol was amended to remove PEGaspargase from the regimen. Two additional patients were enrolled on dose level one.

Primary outcome: Optimal Dose of MLN9708

Time frame: 8 Weeks. Number. Unit: mg

Measure	Modified VXLD Plus MLN9708 n = 5
Value	2.3

Population analysed: All five subjects received the same 2.3 mg oral dose of MLN9708.

Adverse events

Time frame: 8 weeks following last dose.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
(Modified VXLD) Plus MLN9708	4 of 5 (80%)	0 of 5 (0%)	1 of 5

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2020.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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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 L 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?

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 20 inclusion and 14 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: stopped early, as of the sponsor's last update on 22 Jan 2020. 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?

Yes. Results are posted in the registry (first posted 22 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?

Adverse Events. (time frame: Baseline to 30 days post treatment; approximately 8 weeks). 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 NCT01887587.

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 22 Jan 2020.