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OptiMATe: De-escalated Induction Treatment in Primary CNS Lymphoma (OptiMATe)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04931368
Recruitment Status : Recruiting
First Posted : June 18, 2021
Last Update Posted : March 3, 2022
Sponsor:
Collaborators:
German Federal Ministry of Education and Research
University Hospital Freiburg
Information provided by (Responsible Party):
Klinikum Stuttgart

Brief Summary:
This phase III study investigates if a de-escalated induction treatment in newly diagnosed primary CNS lymphoma is superior to the standard MATRix protocol in terms of event free survival.

Condition or disease Intervention/treatment Phase
Primary Central Nervous System Lymphoma Drug: Experimental Treatment: one course Rituximab/HD-Methotrexate, two courses of MATRix Drug: Control intervention: four courses of MATRix Phase 3

Detailed Description:
This phase III study investigates if a de-escalated induction treatment in newly diagnosed primary CNS lymphoma is superior to the standard MATRix protocol in terms of event free survival. Two arms are compared, in the experimental treatment group, participants receive one course of R/HD-MTX, followed by two courses of MATRix and autologous stem cell transplantation. In the control treatment, participants receive four coourses of MATRix followed by autologous stem cell transplantation.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 326 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Optimizing MATRix as Remission Induction in PCNSL: De-escalated Induction Treatment in Newly Diagnosed Primary CNS Lymphoma - a Randomized Phase III Trial
Actual Study Start Date : June 7, 2021
Estimated Primary Completion Date : August 2027
Estimated Study Completion Date : May 2028


Arm Intervention/treatment
Active Comparator: Control treatment (Arm A)
Patients receive four courses of MATRix (Rituximab 2 x 375 mg/m2, HD-Methotrexate 3.5 g/m2, HD-Cytarabine 2 x 2 g/m2, Thiotepa 30 mg/m2; i.v.) as induction treatment. Response assessment with gadolinium-enhanced brain MRI (centrally reviewed) takes place after course two and four. Patient with at least PR proceed to 3rd course of MATRix after first response assessment and to HCT-ASCT (BCNU 400 mg/m2, Thiotepa 4 x 5 mg/kg; i.v.) after second response assessment. Collection of autologous stem cells is planed after the second course of MATRix.
Drug: Control intervention: four courses of MATRix
Patients receive four courses of MATRix as induction treatment.

Experimental: Experimental treatment (Arm B)
As induction treatment, patients receive one course of Rituximab/HD-Methotrexate (Rituximab 375 mg/m2, HD-Methotrexate 3.5 g/m2; i.v.). In the absence of clinical signs of progression, patients proceed to two courses of MATRix (Rituximab 2 x 375 mg/m2, HD-Methotrexate 3.5 g/m2, HD-Cytarabine 2 x 2 g/m2, Thiotepa 30 mg/m2; i.v.) followed by a response assessment with gadolinium-enhanced brain MRI (centrally reviewed). Patients with at least PR will proceed to HCT-ASCT (BCNU 400 mg/m2, thiotepa 4 x 5 mg/kg; i.v.). Collection of autologous stem cells is planed after the first course of MATRix
Drug: Experimental Treatment: one course Rituximab/HD-Methotrexate, two courses of MATRix
De-escalated induction treatment with R/HD-MTX and two courses of MATRix




Primary Outcome Measures :
  1. Event-free survival (EFS) [ Time Frame: up to 24 months after end of treatment ]
    time from randomization to premature end of treatment due to any reason, lymphoma progression or death, whichever occurs first


Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: up to 24 months after end of treatment ]
    time from randomization to death of any course

  2. Progression free survival (PFS) [ Time Frame: up to 24 months after end of treatment ]
    time from randomization until disease progression, relapse or death from any cause

  3. Remission rate prior to consolidation therapy [ Time Frame: assesed at RA II (Arm B: day 18-20 of cycle 2, each cycle is 21 days. Arm A: day 18-20 of cycle 4, each cycle is 21 days) ]
    Remission prior to consolidation therapy will be determined at RA II and will be divided in CR, uCR, PR, CD, PD according to IPCG criteria

  4. Remission rate after consolidation therapy [ Time Frame: 30 days after ASCT ]
    Remission after consolidation therapy will be determined on day 30 after ASCT and will be divided in CR, uCR, PR, SD, PD according to IPCG criteria

  5. rate of patients reaching consolidation therapy [ Time Frame: determined up to 4 weeks after response assessment II ]
    defined as obtaining at least the first dose of consolidation therapy, will be determined after the response assessment II (following 4 cycles of MATRix in the control arm and following 1 cycle of R/HD-MTX and 2 cycles of MATRix in the experimental arm)

  6. Quality of life (QOL), EORTC QLQ-C30, [ Time Frame: up to 24 months after end of treatment ]
    EORTC (European Organization for research and cancer treatment) QLQ-C30, measured during screening, at response assessment II, and with beginning of RA III every 12 months until end of follow-up

  7. Quality of life (QOL), QLQ-BN20 [ Time Frame: up to 24 months after end of treatment ]
    EORTC (European Organization for research and cancer treatment) QLQ-BN20; measured during screening, at response assessment II, and with beginning of RA III every 12 months until end of follow-up


Other Outcome Measures:
  1. Comparison of de-escalated regimen to standard induction therapy regarding safety [ Time Frame: up to 60 days after ASCT ]
    incidence of (Serious) adverse events, laboratory parameters:WBC <2.500/µl and platelets <80.000/μl , vital signs: blood pressure (mmHg), heart rate (bpm)

  2. Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity [ Time Frame: up to 24 months after end of treatment ]
    MoCA (Montreal Cognitive Assesment) performed at screening, EOT and every 12 months until end of follow-up

  3. Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity [ Time Frame: up to 24 months after end of treatment ]
    WAIS III (Wechsler Adult Intelligence scale) counting test performed at screening, EOT and every 12 months until end of follow-up

  4. Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity [ Time Frame: up to 24 months after end of treatment ]
    WAIS III (Wechsler Adult Intelligence scale) subtest similarities and verbal fluency test performed at screening, EOT and every 12 months until end of follow-up

  5. Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity [ Time Frame: up to 24 months after end of treatment ]
    Trail Making Test A and B, performed at screening, EOT and every 12 months until end of follow-up

  6. Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity [ Time Frame: up to 24 months after end of treatment ]
    Brief Test of Attention performed at screening, EOT and every 12 months until end of follow-up

  7. Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity [ Time Frame: up to 24 months after end of treatment ]
    Hopkins Verbal Learning Test performed at screening, EOT and every 12 months until end of follow-up

  8. Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity [ Time Frame: up to 24 months after end of treatment ]
    Grooved Pegboard Test, performed at screening, EOT and every 12 months until end of follow-up

  9. Comparison of de-escalated regimen to standard induction therapy regarding neurotoxicity [ Time Frame: up to 24 months after end of treatment ]
    Rey-Osterrieth-Complex-Figure-Test performed at screening, EOT and every 12 months until end of follow-up

  10. Unplanned hospital admissions [ Time Frame: up to 6 months after EOT visit ]
    Defined as in-patient hospitalization from randomization until 6 months after EOT visit (excluding those for study therapy and/or assessments, placement of an indwelling catheter, social/convenience admissions, respite care, elective or pre-planned treatment/surgery)

  11. Length of hospital stays [ Time Frame: up to 6 months after EOT visit ]
    Measured as number of nights in hospital from randomization and until 6 months after EOT. Hospitalization must be in relation to the disease or the administered treatment or due to toxicity



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Immunocompetent patients with newly diagnosed primary diffuse large B-cell lymphoma of the central nervous system (PCNSL).
  2. Male or female patients aged 18-65 years irrespective of ECOG or 66-70 years with ECOG Performance Status ≤2.
  3. Histologically or cytologically assessed diagnosis of B-cell lymphoma by local pathologist. Diagnostic sample obtained by stereotactic or surgical biopsy, CSF cytology examination or vitrectomy.
  4. Disease exclusively located in the CNS.
  5. At least one measurable lesion.
  6. Previously untreated patients (previous or ongoing steroid treatment admitted)
  7. Negative pregnancy test
  8. Written informed consent obtained according to international guidelines and local laws by patient or authorized legal representative in case patient is temporarily legally not competent due to his or her disease.
  9. Ability to understand the nature of the trial and the trial related procedures and to comply with them.

Exclusion Criteria:

  1. Congenital or acquired immunodeficiency including HIV infection and previous organ transplantation.
  2. Systemic lymphoma manifestation (outside the CNS).
  3. Primary vitreoretinal lymphoma without manifestation in the brain parenchyma or spinal cord
  4. Previous or concurrent malignancies with the exception of surgically cured carcinoma in situ of the cervix, carcinoma of the skin or other kinds of cancer without evidence of disease for at least 5 years.
  5. Previous Non-Hodgkin lymphoma at any time.
  6. Inadequate renal function (clearance < 60 ml/min).
  7. Inadequate bone marrow, cardiac, pulmonary or hepatic function according to investigator´s decision
  8. Active hepatitis B or C disease.
  9. Concurrent treatment with other experimental drugs or participation in an interventional clinical trial with study medication being administered within the last 30 days before the start of this study.
  10. Third space fluid accumulation > 500 ml.
  11. Hypersensitivity to study treatment or any component of the formulation.
  12. Taking any medications that are likely to cause interactions with the study medication
  13. Known or persistent abuse of medication, drugs or alcohol.
  14. Active COVID-19-infection or non-compliance with the prevailing hygiene measures regarding the COVID-19 pandemic
  15. Patients without legal capacity who are unable to understand the nature, significance and consequences of the trial and without designated legal representative.
  16. Previous participation in this trial.
  17. Persons who are in a relationship of dependency/employment with the sponsor and/or the investigator.
  18. Any familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
  19. Current or planned pregnancy, nursing period
  20. For fertile patients: Failure to use one of the following safe methods of contraception: intra-uterine device or hormonal contraception in combination with a mechanical method of contraception.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04931368


Contacts
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Contact: Gerald Illerhaus, Prof +4971127830400 g.illerhaus@klinikum-stuttgart.de
Contact: Elisabeth Schorb, MD +4976127035360 elisabeth.schorb@uniklinik-freiburg.de

Locations
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Germany
Klinikum Stuttgart Recruiting
Stuttgart, Baden-Württemberg, Germany, 70174
Contact: Illerhaus Gerald, Prof.         
Contact    +49711 278-30401    g.illerhaus@klinikum-stuttgart.de   
Sponsors and Collaborators
Klinikum Stuttgart
German Federal Ministry of Education and Research
University Hospital Freiburg
Investigators
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Principal Investigator: Gerald Illerhaus, Prof Klinikum Stuttgart
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Responsible Party: Klinikum Stuttgart
ClinicalTrials.gov Identifier: NCT04931368    
Other Study ID Numbers: SCC215
First Posted: June 18, 2021    Key Record Dates
Last Update Posted: March 3, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: After approval through ethics committee publication of study protocol. Anonymised patient data can be provided upon project related request.
Supporting Materials: Study Protocol
Time Frame: Study protocol: 1st quarter 2021 Not before 2nd quarter 2028: Anonymised patient data
Access Criteria: To get access to anonymised patient data, a research proposal/project plan is required.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Methotrexate
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Nucleic Acid Synthesis Inhibitors