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

NCT00866749 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2006-0375NCI-2012-01650
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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. 1.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.
2. 2.To prospectively evaluate gene hypermethylation status in this group of patients.
3. 3.To prospectively analyze asparaginase activity and anti-asparaginase antibody formation in this population of patients.

Conditions

Lymphoblastic Leukemia; Lymphoblastic Lymphoma

Keywords

acute lymphoblastic leukemia; acute lymphoblastic lymphoma; Leukemia; ALL; 6-Thioguanine; Cyclophosphamide; Cytarabine; Daunorubicin; Doxorubicin; Methotrexate; PEG-L-Asparaginase; Vincristine; Intrathecal Methotrexate; Mercaptopurine

Outcome Measures

Primary Outcomes (3)

• 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%.

  3 Years

• Overall Survival

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

  Up to 12 years

• Participants With a Complete Response (CR)

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

  Up to 1 year

Secondary Outcomes (1)

• Participants Achieving Negative Minimal Residual Disease (MRD)

  up to 3 months

Study Arms (1)

Augmented BFM Therapy

EXPERIMENTAL

Induction + Maintenance: Daunorubicin, Vincristine, PEG-asparaginase, Intrathecal Methotrexate, Cyclophosphamide, Cytarabine, Mercaptopurine, Doxorubicin, Thioguanine

Drug: Daunorubicin; Drug: Vincristine; Drug: PEG-asparaginase; Drug: Intrathecal Methotrexate; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Doxorubicin; Drug: Thioguanine

Interventions

Daunorubicin DRUG

Starting Dose 25 mg/m\^2 by vein weekly

Also known as: Cerubidine®

Augmented BFM Therapy

Vincristine DRUG

Starting Dose 2 mg by vein weekly

Also known as: Vincasar®

Augmented BFM Therapy

PEG-asparaginase DRUG

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

Also known as: Oncaspar®

Augmented BFM Therapy

Intrathecal Methotrexate DRUG

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

Also known as: Rheumatrex®

Augmented BFM Therapy

Cyclophosphamide DRUG

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

Also known as: Cytoxan®

Augmented BFM Therapy

Cytarabine DRUG

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

Also known as: Cytosar-U®

Augmented BFM Therapy

Mercaptopurine DRUG

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

Also known as: Purinethol®

Augmented BFM Therapy

Methotrexate DRUG

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

Also known as: Rheumatrex®

Augmented BFM Therapy

Doxorubicin DRUG

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

Also known as: Adriamycin®

Augmented BFM Therapy

Thioguanine DRUG

60 mg/m2 by mouth daily for two weeks

Also known as: Thioguanine Tabloid®

Augmented BFM Therapy

Eligibility Criteria

• Age: 12 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia

Interventions

Daunorubicin; Vincristine; pegaspargase; Methotrexate; Cyclophosphamide; Cytarabine; Mercaptopurine; Doxorubicin; Thioguanine

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Aminopterin; Pterins; Pteridines; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Sulfhydryl Compounds; Sulfur Compounds; Purines

Results Point of Contact

• Title: Michael Andreeff MD./Professor
• Organization: The University of Texas MD Anderson Cancer Center

mandreeff@mdanderson.org

713-792-7261

Study Officials

• Michael E. Rytting, M.D.

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2009
• First Posted: March 20, 2009
• Study Start: September 12, 2006
• Primary Completion: July 26, 2018
• Study Completion: July 26, 2018
• Last Updated: September 10, 2019
• Results First Posted: September 10, 2019

Record last verified: 2019-08

Locations

US (1)