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Lymphoblastic LeukemiaPhase 2NCT00866749

Augmented Berlin-Frankfurt-Munster (BFM) Therapy for Adolescent/Young Adults With Acute Lymphoblastic Leukemia or Acute Lymphoblastic Lymphoma

A Phase 2 study testing Daunorubicin, Vincristine and PEG-asparaginase in people with Lymphoblastic Leukemia and Lymphoblastic Lymphoma, run by M.D. Anderson 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

Objectives: A. Primary objective: 1 To assess the feasibility and the effectiveness of pediatric type therapy (augmented BFM) in patients age 12 through 40 with untreated precursor-B or T acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL). B. Secondary objective: 1. Read more about this study

Who is it for?
Ages 12 to 40 years
What is being tested?
Daunorubicin, Vincristine and PEG-asparaginase
Could I receive a placebo?
No, everyone receives an active treatment
How many people
120 participants
Where
1 siteUnited States
Study dates
12 Sep 2006to 26 Jul 2018
Phase
Phase 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 12 to 40 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Patients must have precursor-B or T-lymphoblastic leukemia or lymphoblastic lymphoma.
  • Patients must be untreated or have had only one prior chemotherapy regimen for ALL or LL . Previously treated patients will be analyzed separately.
  • Age between 12 to 40 years old
  • Patients with Central Nervous System (CNS) disease or testicular disease are eligible.
  • Intrathecal therapy with cytarabine is allowed prior to registration for patient convenience. This is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture. Systemic chemotherapy must begin within 72 hours of the first intrathecal treatment.
  • Signed informed consent prior to the start of systemic therapy. In the event of enrollment of a minor patient, an attempt to obtain assent from the patient must be documented, and parental consent must be signed.
Show all 10Show fewer
  • Echocardiogram should be done within 72 hours of starting therapy if there are cardiac risk factors (e.g., history of hypertension or of myocardial infarction)
  • Creatinine should be < 3 mg/dL bilirubin < 3 mg/dl unless felt to be due to disease
  • Zubrod Performance status of <3
  • Patients who received steroids more than 72 hours prior to study enrollment are eligible but will be analyzed separately

Who cannot join

  • Age less than twelve years of age or greater than 40 years.
  • More than one prior treatment regimen for ALL or LL.
  • The patient is pregnant or unwilling to practice appropriate birth control.
  • Presence of the Philadelphia chromosome t(9;22)

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Augmented Berlin-Frankfurt-Munster Therapy for Adolescents/Young Adults With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

Objectives:

  1. Primary objective:

1 To assess the feasibility and the effectiveness of pediatric type therapy (augmented BFM) in patients age 12 through 40 with untreated precursor-B or T acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LL).

  1. Secondary objective:
  2. To evaluate the prognostic significance of minimal residual disease in bone marrow samples at the end of induction and at the end of consolidation in this group of patients.
  3. To prospectively evaluate gene hypermethylation status in this group of patients.
  4. To prospectively analyze asparaginase activity and anti-asparaginase antibody formation in this population of patients.
Read the detailed description

Induction:

During Induction, you will receive augmented Berlin-Frankfurt-Munster chemotherapy, which is made up of a combination of Cerubidine®, Daunorubicin Hydrochloride (daunorubicin), Oncovin® (vincristine), prednisone, dexamethasone, Oncaspar® (PEG Asparaginase), and MTX amethopterin (methotrexate). All of these drugs are designed to interfere with the multiplication of cancer cells to cause them to die and to keep the cancer from coming back.

If you are found to be eligible to take part in this study, on Day 1 or during the spinal tap procedure, you will be given cytarabine as an injection in your spinal fluid. Within 3 days, you will begin the Induction course, which will last for 4 weeks.

Daunorubicin and vincristine will be given through a needle in your vein on Days 1, 8,15, and 22. During the first week of therapy, you will be given 1 infusion of PEG Asparaginase by vein. You will take prednisone by mouth on Days 1-28. Methotrexate will be injected into your spinal fluid on Weeks 2 and 5 during your spinal tap. Cerebrospinal fluid (CSF) studies will be sent with each spinal tap to test the fluid for leukemia. If there is disease in your spinal fluid before starting the treatment, you will be given additional methotrexate doses once a week until there is no disease present. You will continue to receive methotrexate in spinal taps every other week for 8 doses, then monthly for 6 doses.

Blood (about 3 teaspoons) will be drawn multiple times during the study for routine tests. You will have a bone marrow aspirate or biopsy on Days 15 and 29 and then as needed to confirm remission.

If you have less than 5% immature cells in the bone marrow, 1 week after Induction, you will continue treatment with Consolidation 1. If you achieved remission after 4 weeks of Induction treatment, you will then have treatment with Consolidation 1, which will be discussed in a separate informed consent document.

If you have LL and had no bone marrow involvement at screening, you will have a chest x-ray, CT scans, and PET scans to measure the disease. Consolidation 1 and other phases of chemotherapy will be discussed in a separate informed consent document.

If you still have more than 5% leukemia cells in the bone marrow after Induction therapy, you will receive 2 extra weeks of therapy called "Extended Induction" before going to the next phase of therapy. You will receive daunorubicin by vein on Day 1. You will receive vincristine on Weeks 1 and 2 by vein. You will take prednisone by mouth on Days 1-14. You will receive PEG Asparaginase by vein in the first week of the Extended Induction. Blood (about 3 teaspoons) will be drawn weekly during the Extended Induction period for routine tests.

At the end of the Extended Induction period, you will have a physical exam and a bone marrow aspirate or biopsy to learn your response to treatment.

After Extended Induction, if the disease is in remission, then you will have 1 course of Consolidation 1, 2 courses of Consolidation 2, and 2 courses of Consolidation 3 before proceeding to Maintenance therapy. A separate discussion and informed consent document for Consolidation and Maintenance will be provided.

Length of Study:

You may remain on study for as long as you are benefiting. However, if after Extended Induction, the disease is not in remission, you will be taken off study, and your doctor will discuss other treatment options with you.

You may be taken off study if the disease gets worse or comes back during treatment, intolerable side effects occur, new information becomes available to your study doctor, if your doctor thinks it is in your best interest, or if you do not attend your appointments, which are scheduled at least once every 3 months.

This is an investigational study. The chemotherapy drugs used in this study are FDA approved and commercially available. Up to 125 patients will take part in this study. All will be enrolled at MD Anderson.

Consolidation and Maintenance:

During Consolidation, you will receive cyclophosphamide, cytarabine, 6-mercaptopurine, vincristine, PEG asparaginase, methotrexate, doxorubicin, 6-thioguanine, and dexamethasone. During Maintenance, you will receive, vincristine, dexamethasone, 6-mercaptopurine, and methotrexate. All of these drugs are designed to interfere with the multiplication of cancer cells to cause them to die and to keep the cancer from coming back.

If you achieved remission after 4 weeks of induction treatment, you will have treatment with Consolidation 1, Consolidation 2, Consolidation 3 (Parts A and B), and then you will proceed to Maintenance therapy.

If the level of blast cells in your blood is above a certain level at Day 15 of Induction but you achieved complete remission by Day 29, or if you achieved remission after 6 weeks of induction plus extended induction, then you will receive 1 course of Consolidation 1, 2 courses of Consolidation 2, 2 courses of Consolidation 3 (Parts A and B), and then you will proceed to maintenance therapy.

Consolidation 1 will last for 8 weeks (2 months). You will receive cyclophosphamide through a needle in your vein on Weeks 1 and 5. Cytarabine will be given as an injection just beneath the skin or by vein on or around Days 1-4 and Days 8-11 of each month. 6-Mercaptopurine will be taken by mouth on Days 1-14 of each month. Vincristine will be given by vein on Weeks 3-4 of each month. PEG Asparaginase will be given by vein on Week 3 and 6 of each month. You will receive methotrexate through a needle through your spine weekly during Month 1 only. Blood (about 3 teaspoons) will be drawn for routine tests. You will have a spinal tap with spinal fluid tests during the intrathecal methotrexate dose. A spinal tap (also called a lumbar puncture) is when a special needle is inserted into the lower back through the space between the bones to draw a sample of the fluid that surrounds the spinal cord. You will have a bone marrow aspiration at the end of Month 2. To collect a bone marrow aspirate, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow is withdrawn through a large needle.

Consolidation 2 will last for 7 weeks. You will receive vincristine and methotrexate by vein every 10 plus or minus 2 days for 5 doses. You will receive PEG Asparaginase by vein in Weeks 1 and 4. You will receive intrathecal methotrexate in Weeks 1 and 5. You will have a spinal tap with spinal fluid tests during the intrathecal methotrexate dose. Blood (about 3 teaspoons) will be drawn every 2 weeks for routine tests.

Consolidation 3 (Part A) will last for 4 weeks. You will receive vincristine and Doxorubicin by vein in Weeks 1, 2 and 3. Dexamethasone will be taken by mouth on Days 1-7 and Days 15-21. You will receive PEG Asparaginase by vein on Week 1. You will receive intrathecal methotrexate in Week 1.

Consolidation 3 (Part B) will last for 4 weeks. You will receive cyclophosphamide by vein in Week 1. You will receive cytarabine by vein or as an injection for 4 days in a row in Weeks 1-2. You will take 6-Thioguanine by mouth every day for the first 2 weeks. You will receive intrathecal methotrexate in Weeks 1 and 2. You will receive vincristine by vein on Weeks 3 and 4. You will receive PEG Asparaginase by vein on Week 3.

During Consolidation 3 (Part A and B), blood (about 3 teaspoons) will be drawn at least weekly for routine tests. Spinal fluid tests will be sent with each intrathecal methotrexate dose. Spinal taps will be done during each intrathecal chemotherapy dose

Once you finish Consolidation, you will proceed to maintenance therapy.

The Maintenance period for ALL patients will last for 24 months. If you have ALL, you will receive vincristine by vein every month. You will take dexamethasone by mouth for 5 days every month. You will take 6-Mercaptopurine by mouth once daily. You will take methotrexate by mouth every week. You will receive intrathecal methotrexate every 3 months for the first 12 months of maintenance. You will have a spinal tap with spinal fluid tests during the intrathecal methotrexate dose.

Maintenance for patients with LL will also last for 24 months. If you have LL, you will receive vincristine by vein every month. You will take dexamethasone by mouth for 5 days every month.

You will take 6-Mercaptopurine by mouth once daily. You will take methotrexate by mouth every week.

During the Maintenance period, all participants will have blood samples (about 1 to 3 teaspoons each time) drawn every 3 months for routine tests.

If you have LL, you will have an additional positron emission tomography (PET) scan and computed tomography (CT) scan at the end of the Maintenance period.

Follow-Up Visits:

Your study doctor will inform you of your follow-up visits in the clinic. At each follow-up visit there will be a physical exam and complete blood count. You will be followed-up for the next 3 years after your the last dose of your chemotherapy.

Length of Study:

You may remain on study for as long as you are benefiting. You may be taken off study if the disease gets worse or comes back during treatment, intolerable side effects occur, new information becomes available to your study doctor, if your doctor thinks it is in your best interest, or if you do not attend your appointments, which are scheduled at least once every 3 months.

This is an investigational study. The chemotherapy drugs used in this study are all FDA approved and commercially available. Up to 125 patients will take part in this study. All will be enrolled at MD Anderson.

Being tested
Daunorubicin, Vincristine, PEG-asparaginase, Intrathecal Methotrexate, Cyclophosphamide
Keywords
acute lymphoblastic leukemia, acute lymphoblastic lymphoma, Leukemia, ALL, 6-Thioguanine, Cyclophosphamide, Cytarabine, Daunorubicin, Doxorubicin, Methotrexate, PEG-L-Asparaginase, Vincristine, Intrathecal Methotrexate, Mercaptopurine
Medical subject headings
Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia

What participants receive

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

  • DaunorubicinDrug

    Also called Cerubidine®

    Starting Dose 25 mg/m^2 by vein weekly

  • VincristineDrug

    Also called Vincasar®

    Starting Dose 2 mg by vein weekly

  • PEG-asparaginaseDrug

    Also called Oncaspar®

    Starting Dose 2000 International units/m2 by vein in week 1

  • Intrathecal MethotrexateDrug

    Also called Rheumatrex®

    Starting Dose 12 mg on week 2 and week 5 injected into spinal fluid

  • CyclophosphamideDrug

    Also called Cytoxan®

    Starting Dose 1g/m2 by vein in weeks 1 and 5

  • CytarabineDrug

    Also called Cytosar-U®

    75 mg/m2 subcutaneous or by vein for four consecutive days on days 1-4 and days 8-11 of both months

  • MercaptopurineDrug

    Also called Purinethol®

    Starting Dose 60 mg/m2 by mouth on days 1-14 of each month

  • MethotrexateDrug

    Also called Rheumatrex®

    Starting Dose at 100 mg/m2 by vein and escalating by 50 mg/m2/dose every 10

    +/- 2 days for 5 doses to toxicity (e.g myelosuppression or mucositis grade 3

  • DoxorubicinDrug

    Also called Adriamycin®

    25 mg/m2 by vein in weeks 1, 2 and 3

  • ThioguanineDrug

    Also called Thioguanine Tabloid®

    60 mg/m2 by mouth daily for two weeks

Study groups in NCT00866749
Study groupRoleWhat they receive
Augmented BFM TherapyExperimentalInduction + Maintenance: Daunorubicin, Vincristine, PEG-asparaginase, Intrathecal Methotrexate, Cyclophosphamide, Cytarabine, Mercaptopurine, Doxorubicin, Thioguanine
Receives: Drug: Daunorubicin; Drug: Vincristine; Drug: PEG-asparaginase; Drug: Intrathecal Methotrexate; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Doxorubicin; Drug: Thioguanine

What is being measured

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

  1. 3-Year Event-Free Survival (EFS)

    3-year EFS was calculated based on the participants with a complete response (CR). Study regimen considered successful if it exhibits a 3-year EFS rate greater than 60% and response rate no less than 90% with Grade III-IV infectious toxicity rate in induction no more than 33%.

    Measured: 3 Years

  2. Overall Survival

    Overall Survival defined: Time from date of treatment start until date of death due to any cause or last Follow-up.

    Measured: Up to 12 years

  3. Participants With a Complete Response (CR)

    Complete Response defined as: Bone Marrow blasts </= 5%, Platelets >/= 100 and an Absolute Neutrophil Count (ANC) >/= 1000

    Measured: Up to 1 year

Secondary outcomes (1)

  1. Participants Achieving Negative Minimal Residual Disease (MRD)

    To evaluate the prognostic significance of minimal residual disease (MRD) in bone marrow samples of participants who achieved a complete response (CR) at the end of induction (day 29) and at the end of consolidation (day 84) in this group of patients.

    Measured: up to 3 months

Timeline

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

  1. First posted20 Mar 2009 (estimated)
  2. Study start12 Sep 2006
  3. Primary completion26 Jul 2018
  4. Study completion26 Jul 2018

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
120 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00866749
Sponsor's protocol ID
2006-0375
Other IDs
NCI-2012-01650
Status last verified
Aug 2019
First submitted
19 Mar 2009
Last updated
10 Sep 2019
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Daunorubicin, Vincristine and PEG-asparaginase in people with Lymphoblastic Leukemia and Lymphoblastic Lymphoma, run by M.D. Anderson 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 10 inclusion and 4 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 10 Sep 2019. 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 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 10 Sep 2019). 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?

3-Year Event-Free Survival (EFS) (time frame: 3 Years). The study lists 3 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 NCT00866749.

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 10 Sep 2019.

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