CHemoImmunotherapy With Early Central Nervous System (CNS) Prophylaxis (CHIC)

• ClinicalTrials.gov Identifier: NCT01325194
• Recruitment Status: Completed
• First Posted: March 29, 2011
• Last Update Posted: March 3, 2020
• Sponsor: Nordic Lymphoma Group
• Collaborators: Mundipharma Pte Ltd.; Amgen
• Information provided by (Responsible Party): Nordic Lymphoma Group

Study Description

Brief Summary:

The purpose is to test whether early central nervous system (CNS) prophylaxis given at the beginning of therapy for young high risk diffuse large B-cell lymphoma (DLBCL) patients is feasible and could reduce the risk of CNS relapses. Early CNS prophylaxis with two courses high dose methotrexate (HD-MTX) in combination with rituximab-cyclophosphamide-doxorubicin-vincristine-prednison (R-CHOP) is followed by four courses of R-CHOP14 and etoposide (E) and one course of HD-Ara-C. In addition the patients will receive three courses of liposomal cytarabine intrathecally. The results will be compared to a recent Nordic CRY-04 study. Shifting of CNS prophylaxis to the beginning of the therapy offers a potential to overcome the subclinical disease and thus reduce the risk of early clinical CNS recurrence. As flow cytometry (FCM) can improve the sensitivity for detecting occult leptomeningeal disease over cytology , FCM from cerebrospinal fluid will be incorporated into the staging procedures.

Condition or disease	Intervention/treatment	Phase
Primary Disease	Drug: liposomal cytarabine	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 143 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Dose Densified Chemoimmunotherapy With Early CNS Prophylaxis in Patients Less Than 65 Years With High Risk (aaIPI≥ 2) Diffuse Large B-Cell Lymphoma
• Actual Study Start Date: March 2011
• Actual Primary Completion Date: November 2018
• Actual Study Completion Date: December 31, 2019

Arms and Interventions

Arm	Intervention/treatment
Experimental: CNS prophylaxis	Drug: liposomal cytarabine; 50 mg intrathecally three times; Other Name: Depocyte

Outcome Measures

Primary Outcome Measures :

1. Time to treatment failure [ Time Frame: 3 and 5 years ]

Secondary Outcome Measures :

1. Maximal hematological, gastrointestinal, neuronal and other toxicities [ Time Frame: Treatment period (5 years) ]
2. Clinical response rate [ Time Frame: Treatment period (5 years) ]
3. Incidence of central nervous system(CNS) relapse in cerebrospinal fluid (CSF )cytology neg/flow cytometry positive cases [ Time Frame: 3 and 5 years ]
4. Incidence of CNS relapse in a subgroup of patients with more than one extranodal site and elevated lactate dehydrogenase (LDH) [ Time Frame: 3 and 5 years ]
5. Progression free survival [ Time Frame: 3 and 5 years ]
6. Overall survival [ Time Frame: 3 and 5 years ]
7. Molecular predictors [ Time Frame: 3 years ]
8. CNS relapse rate [ Time Frame: 1,5 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 64 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age ≥ 18 - < 65 years. Histologically confirmed CD20+ diffuse large B-cell lymphoma (DLBCL) based on WHO 2008 Lymphoma Classification
• Follicular lymphomas (FLs) grade 3b is allowed

Patients in at least stage II with age adjusted international prognostic score (IPI score) of 2 or 3:

• Stage III /IV and elevated LDH
• Stage III/IV and WHO performance status 2 - 3
• Stage II and elevated LDH and WHO performance status 2 - 3 And/or patients with
• More than one extranodal site
• Testicular lymphoma, stage IIE and higher
• Paranasal sinus and orbital lymphoma with destruction of bone
• Large cell infiltration of the bone marrow

Exclusion Criteria:

• Severe cardiac disease: cardiac function grade 3-4
• Impaired liver, renal or other organ function not caused by lymphoma, which will interfere with the treatment schedule
• Pregnancy/lactation
• Men and women of reproductive potential not agreeing to use an acceptable method of birth control during treatment and for six months after completion of treatment
• Patients with other severe medical problems and with an expected short survival for non-lymphoma reasons
• Known HIV positivity
• Uncontrolled infectious disease, including meningeal infection
• Active cancer except basal cell carcinoma and cervical carcinoma in situ during the last five years
• Earlier treatment containing anthracyclins
• Psychiatric or mental disorder which make the patient unable to give an informed consent and/or adhere to the protocol
• CNS disease as diagnosed by MRI or cerebrospinal fluid (CSF) cytology. Positive CSF flow cytometry below diagnostic threshold level by cytology is allowed
• Pleural or peritoneal fluid that cannot be drained safely
• Hypersensitivity to the active substance or any of the other ingredients
• Patients participating in other clinical studies, unless followed for survival

Contacts and Locations

Locations

Denmark

Department of Hematology, Århus University Hospital

Århus, Denmark

Finland

Department of Oncology, Helsinki University Central Hospital

Helsinki, Finland

Norway

Department of Oncology, Oslo University Hospital

Oslo, Norway

Sweden

Department of Oncology, Lund University Hospital

Lund, Sweden

Sponsors and Collaborators

Nordic Lymphoma Group

Mundipharma Pte Ltd.

Amgen

More Information

Additional Information:

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Leppä S, Jørgensen J, Tierens A, Meriranta L, Østlie I, de Nully Brown P, Fagerli UM, Larsen TS, Mannisto S, Munksgaard L, Maisenhölder M, Vasala K, Meyer P, Jerkeman M, Björkholm M, Fluge Ø, Jyrkkiö S, Liestøl K, Ralfkiaer E, Spetalen S, Beiske K, Karjalainen-Lindsberg ML, Holte H. Patients with high-risk DLBCL benefit from dose-dense immunochemotherapy combined with early systemic CNS prophylaxis. Blood Adv. 2020 May 12;4(9):1906-1915. doi: 10.1182/bloodadvances.2020001518.

Autio M, Leivonen SK, Brück O, Mustjoki S, Mészáros Jørgensen J, Karjalainen-Lindsberg ML, Beiske K, Holte H, Pellinen T, Leppä S. Immune cell constitution in the tumor microenvironment predicts the outcome in diffuse large B-cell lymphoma. Haematologica. 2021 Mar 1;106(3):718-729. doi: 10.3324/haematol.2019.243626.

• Responsible Party: Nordic Lymphoma Group
• ClinicalTrials.gov Identifier: NCT01325194
• Other Study ID Numbers: NLG-LBC-05
• First Posted: March 29, 2011
• Last Update Posted: March 3, 2020
• Last Verified: March 2020

Keywords provided by Nordic Lymphoma Group:

DLBCL; FL grade 3B; high risk; CNS prophylaxis; chemoimmunotherapy

Additional relevant MeSH terms:

Cytarabine; Antimetabolites, Antineoplastic; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antiviral Agents; Anti-Infective Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs