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Acute Lymphoblastic LeukemiaPhase 1NCT02228772

Phase I Study of MLN 9708 in Addition to Chemotherapy for the Treatment of Acute Lymphoblastic Leukemia in Older Adults

A Phase 1 study testing MLN 9708, Vincristine and Cytarabine in people with Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma, run by Massachusetts General Hospital at 3 sites 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

This research study is evaluating a combination of drugs considered standard treatment for children and young adults with acute lymphoblastic leukemia (ALL), in combination with a new drug called MLN 9708. Read more about this study

Who is it for?
Ages 51 to 75 years
What is being tested?
MLN 9708, Vincristine and Cytarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
3 sitesUnited States
Study dates
Dec 2014to Nov 2019
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 51 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Acute lymphoblastic leukemia, excluding known mature B-cell ALL by the presence of any of the following: surface immunoglobulin, L3 morphology, t(8;14)(q24;q32), t(8;22), or t(2;8).
  • Patients with mature B-cell ALL will be removed from the protocol as soon as that diagnosis is made and should be treated on a B-cell leukemia (Burkitt's) protocol. NOTE: Patients with T-cell surface markers and a t(8;14)(q24;q11) remain eligible.
  • Patients with lymphoblastic lymphoma are also eligible
  • No prior anti-leukemic therapy except the following are allowed: <1 week of corticosteroids, or hydroxyurea or emergent leukopheresis. Longer steroid use for diseases other than leukemia is permitted.
  • Age 51- 75 years
  • Voluntary written consent must be given before performance of any study-related procedures not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care.
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  • If patient is known to be HIV positive, they will not be eligible for the protocol. HIV testing is not mandatory prior to protocol enrollment.
  • Patients whose comorbid medical condition, in the investigator's opinion, would make participation in this trial and adherence to the protocol guidelines difficult should be excluded.
  • Patients with an active psychiatric or mental illness making informed consent or careful clinical follow-up unlikely are excluded.
  • Ejection fraction ≥ 45%
  • Creatinine<2.0 times upper limit of normal
  • Total bilirubin < 1.5 times upper limit of normal except for known conjugation diseases such as Gilbert's, ALT and AST <3.0 times upper limit of normal. Direct bilirubin is not an inclusion criteria.
  • ECOG performance status of 0, 1, 2
  • Non pregnant and non lactating 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, 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 [eg, calendar, ovulation, symptothermal, post-ovulation methods] and withdrawal are not acceptable methods of contraception.)
  • Male patients, even if surgically sterilized (i.e., 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
  • 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 (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.
  • Female patients who are lactating or have a positive serum pregnancy test during the screening period.
  • Major surgery within 14 days before enrollment. Biopsies and line placement procedures are not exclusion criteria.
  • Radiotherapy within 14 days before enrollment. Radiotherapy is excluded during induction and consolidation 1 while receiving MLN 9708.
  • Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure, unstable angina, or myocardial infarction within the past 6 months.
  • Active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive. Hepatitis and HIV testing are not required prior to the start of treatment.
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  • Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
  • Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent.
  • Patient has ≥ Grade 3 peripheral neuropathy, or Grade 2 with pain on clinical examination during the screening period.
  • Known GI disease or GI procedure that could interfere with the oral absorption or tolerance of MLN9708 including difficulty swallowing.
  • 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.
  • Participation in other clinical trials, including those with other investigational agents not included in this trial, within 21days of the start of this trial and throughout induction and consolidation 1 portions of this trial (while on MLN 9708). Patients may enroll in transplant and post transplant studies after consolidation 1 treatment (See Section 6.5).
  • Systemic treatment, within 14 days before the first dose of MLN9708, with strong inhibitors of CYP1A2 (fluvoxamine, enoxacin), strong inhibitors of CYP3A (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. Ciprofloxocin should not be administered for at least 2 days before MLN 9708 administration. Extended release ciprofloxocin should not be administered for at least 3 days prior to MLN 9708 administration.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

This research study is evaluating a combination of drugs considered standard treatment for children and young adults with acute lymphoblastic leukemia (ALL), in combination with a new drug called MLN 9708. Additionally, the study is also evaluating if bone marrow or stem cell transplantation, which will be given to some participants, helps to prevent ALL from returning.

Read the detailed description

In this research study, the investigators are studying the optimal dose of the drug MLN 9708 when given with a standard multi-drug regimen. In the first part of the study, up to 18 participants will be enrolled at different doses of MLN 9708. Once the maximally tolerated (highest, safest dose) is established, an additional 10 participants will be enrolled.

Additionally, bone marrow (tissue found in the inside of bones) or stem cell transplantation will be given to some participants to study whether it helps to prevent ALL from returning.

The study treatment consists of several different stages

  • Induction
  • Consolidation 1
  • Or Stem Cell or Bone Marrow Transplant (if you are eligible based on your medical condition and the availability of a matched stem cell donor)
  • Or If you do not have a transplant:
  • CNS Therapy
  • Consolidation 2
  • Continuation Therapy
Being tested
MLN 9708, Vincristine, Cytarabine, Doxorubicin, Mercaptopurine
Keywords
Acute lymphoblastic Leukemia, Lymphoblastic lymphoma, B-cell Adult Acute Lymphoblastic Leukemia, T-cell Adult Acute Lymphoblastic Leukemia
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

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

  • MLN 9708Drug

    Also called Ixazomib

    Patients will received standard chemotherapy as well as MLN 9708 in escalating doses.

  • VincristineDrug

    Also called Oncovin, Vincasar PFS, Vincrex, Vincristine sulfate

    Standard chemotherapy dosage and duration

  • CytarabineDrug

    Also called Ara-C, Cytosar-U, Cytosine arabinoside

    Standard chemotherapy dosage and duration

  • DoxorubicinDrug

    Also called Adriamycin, Rubex

    Standard chemotherapy dosage and duration

  • MercaptopurineDrug

    Also called 6-MP, Purinethol, Purixan

    Standard chemotherapy dosage and duration

  • CyclophosphamideDrug

    Also called Cytoxan, Neosar, CTX

    Standard chemotherapy dosage and duration

  • MethotrexateDrug

    Also called Folex, Mexate, MTX, Methotrex (formerly Amethopterin)

    Standard chemotherapy dosage and duration

Study groups in NCT02228772
Study groupRoleWhat they receive
MLN 9708Experimental* Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation. * MLN 9708 will be given with standard multi-drug regimen for ALL . MLN 9708 will be administered on determined days during Induction therapy cycle and Consolidation cycle. If remission occurs and if eligible, the next stage with be either Stem Cell or Bone Marrow Transplant. * If not eligible to receive a transplant, the participant will continue on this study for the next 3 stages. * CNS Therapy * Consolidation 2 * Continuation Therapy No further MLN9708, the investigational drug, will be given after Consolidation 1 Standard chemotherapy -Vincristine, Cytarabine, Doxorubicin, Mercaptopurine, Cyclophosphamide, Methotrexate
Receives: Drug: MLN 9708; Drug: Vincristine; Drug: Cytarabine; Drug: Doxorubicin; Drug: Mercaptopurine; Drug: Cyclophosphamide; Drug: Methotrexate

What is being measured

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

  1. Maximum Dose Tolerated of MLN 9708

    Measured: 2 Years

Secondary outcomes (5)

  1. Percentage of Patient with Complete Remission (CR) rate at the end of induction therapy

    Measured: 30 Days

  2. Percentage of Participants with Disease Free Survival

    Measured: 2 Years

  3. Rate of Overall survival (OS)

    Measured: 1 Year, 2 Year, 3 Year

  4. Complete Remission Rate

    Measured: 2 Years

  5. Rate of Toxicity

    Assess adverse events, serious adverse events, neurotoxicity grading

    Measured: 2 Years

Timeline

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

  1. First posted29 Aug 2014 (estimated)
  2. Study startDec 2014
  3. Primary completionOct 2016
  4. Study completionNov 2019

Resources

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
19 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02228772
Sponsor's protocol ID
14-200
Status last verified
Nov 2019
First submitted
23 Aug 2014
Last updated
26 Nov 2019
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MLN 9708, Vincristine and Cytarabine in people with Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma, run by Massachusetts General Hospital at 3 sites 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 23 inclusion and 13 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 26 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites 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?

Maximum Dose Tolerated of MLN 9708 (time frame: 2 Years). 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 NCT02228772.

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 26 Nov 2019.

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