R-ICE and High-Dose Cyclophosphamide With PET/CT for Diffuse Large B-Cell Non-Hodgkin's Lymphoma

• ClinicalTrials.gov Identifier: NCT00809341
• Recruitment Status: Terminated
• First Posted: December 17, 2008
• Results First Posted: September 25, 2018
• Last Update Posted: September 25, 2018
• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Collaborator: Genentech, Inc.
• Information provided by (Responsible Party): Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Description

Brief Summary:

This research is being done to see if a PET scan that is obtained after 3 cycles of a standard chemotherapy regimen can help guide treatment for patients with a blood disease called Non-Hodgkin's Lymphoma.

The standard treatment for newly diagnosed lymphoma is 6 to 8 cycles of chemotherapy like the CHOP combination (Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone). This regimen can cure about half of patients with lymphoma, but in many others disease relapses (comes back). Relapses are generally treated with more chemotherapy.

We believe that a PET scan (a type of imaging study that "lights up" in areas of cells with high activity such as lymphoma), may identify patients early who are at high risk of relapse.

The purpose of this research study is to find out if people whose treatment is changed early to an intensification regimen (high dose chemotherapy) based on a positive PET scan will have longer remissions than they would if they did not receive that high dose chemotherapy.

Condition or disease	Intervention/treatment	Phase
Non-Hodgkin's Lymphoma	Biological: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Drug: Ifosfamide; Drug: Carboplatin; Drug: Etoposide; Drug: High-dose cyclophosphamide; Procedure: PET scan	Phase 2

Detailed Description:

Patients will receive 3 cycles of chemotherapy prior to mid-treatment PET-CT. Rituximab-CHOP, or an equivalent regimen must be used. During the third cycle of Rituximab-CHOP chemotherapy, a PET-CT scan will be performed. The PET scan will be designated as negative or positive. Based on the results, patients will either complete standard dose therapy or receive two cycles of R-ICE followed by high dose cyclophosphamide and rituximab.

A repeat PET-CT is required between 4 to 6 weeks following treatment completion. Patients will be followed-up every 4 months for 2 years, then every 6 months for one year, then annually until 5 years.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 27 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Treatment Intensification With R-ICE and High-Dose Cyclophosphamide for Diffuse Large B-Cell Non-Hodgkin's Lymphoma Based on Early [18F] FDG-PET Scanning
• Study Start Date: January 2009
• Actual Primary Completion Date: April 2014
• Actual Study Completion Date: April 2014

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: PET Negative; R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or an equivalent anthracycline-containing regimen for 3 cycles, followed by PET scan. Participants with a negative PET scan will complete their chemotherapy regimen as prescribed by their oncologist.	Biological: Rituximab; 375 mg/m^2 on Day 1 of each cycle as part of R-CHOP or R-ICE. Also given 375 mg/m^2 on Days 1, 30, and 37 as part of HiCy.; Other Name: Rituxan; Drug: Cyclophosphamide; 750 mg/m^2 on Day 1 of each cycle as part of R-CHOP.; Other Name: Cytoxan; Drug: Doxorubicin; 50 mg/m^2 on Day 1 of each cycle as part of R-CHOP.; Other Names: Adriamycin; Hydroxydaunorubicin; Drug: Vincristine; 1.4 mg/m^2 on Day 1 of each cycle as part of R-CHOP.; Other Name: Oncovin; Drug: Prednisone; 100 mg/day on Days 1-5 of each cycle as part of R-CHOP.; Procedure: PET scan; Performed once between Days 16-20 of cycle 3 of R-CHOP.; Other Name: FDG-PET
Active Comparator: PET Positive; R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) or an equivalent anthracycline-containing regimen for 3 cycles, followed by PET scan. Participants with a positive PET scan will receive two cycles of R-ICE (rituximab, ifosfamide, carboplatin, etoposide) followed by HiCy (high-dose cyclophosphamide).	Biological: Rituximab; 375 mg/m^2 on Day 1 of each cycle as part of R-CHOP or R-ICE. Also given 375 mg/m^2 on Days 1, 30, and 37 as part of HiCy.; Other Name: Rituxan; Drug: Cyclophosphamide; 750 mg/m^2 on Day 1 of each cycle as part of R-CHOP.; Other Name: Cytoxan; Drug: Doxorubicin; 50 mg/m^2 on Day 1 of each cycle as part of R-CHOP.; Other Names: Adriamycin; Hydroxydaunorubicin; Drug: Vincristine; 1.4 mg/m^2 on Day 1 of each cycle as part of R-CHOP.; Other Name: Oncovin; Drug: Prednisone; 100 mg/day on Days 1-5 of each cycle as part of R-CHOP.; Drug: Ifosfamide; 2000 mg/m^2/day on Days 1-3 of each cycle as part of R-CHOP.; Other Name: Ifex; Drug: Carboplatin; Given on Day 2 of each cycle as part of R-CHOP. Dosed according to renal function.; Other Name: Paraplatin; Drug: Etoposide; 100 mg/m^2/day on Days 1-3 of each cycle as part of R-CHOP.; Other Name: VP-16; Drug: High-dose cyclophosphamide; 50 mg/kg/day on Days 2-5 of HiCy.; Other Name: HiCy; Procedure: PET scan; Performed once between Days 16-20 of cycle 3 of R-CHOP.; Other Name: FDG-PET

Outcome Measures

Primary Outcome Measures :

1. Event-free Survival in Patient Receiving Early Treatment Intensification Based on a Positive Mid-treatment PET Scan [ Time Frame: 2 years ]

Secondary Outcome Measures :

1. Overall Survival in Patients Whose Treatment is Determined on the Basis of a Mid-treatment [18F] FDG-PET Scan Result. [ Time Frame: 5 years ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• One of the following Biopsy-confirmed, aggressive non-Hodgkin's lymphoma

  1. Diffuse large B-cell lymphoma
  2. Mediastinal (thymic) B-cell lymphoma
• Any stage (I through IV) as defined by the Ann Arbor staging system
• ECOG performance status of 0 to 2
• Radiographically measurable disease
• No more than 3 cycles of chemotherapy for lymphoma
• Greater than or equal to 18 years
• Adequate pulmonary, cardiac, hepatic, or renal function
• HIV antibody negative
• Women- Not pregnant or breastfeeding
• Men of reproductive potential must agree to use contraception

Exclusion Criteria:

• Patients with the following aggressive lymphomas are not eligible:

  1. Mantle cell
  2. Lymphoblastic
  3. Burkitt's
  4. Mycosis fungoides/Sezary's syndrome
  5. HTLV-1 associated T-cell leukemia/lymphoma
  6. Primary CNS lymphoma
  7. HIV-associated lymphoma
  8. Transformed lymphomas
  9. Immunodeficiency-associated lymphomas
• Previous diagnosis of another hematologic malignancies
• Progressive disease on CHOP or Rituximab-CHOP
• Active CNS involvement by lymphoma
• Serious co-morbid disease that could preclude full participation in study

Contacts and Locations

Locations

United States, Maryland

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States, 21231

Sponsors and Collaborators

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Genentech, Inc.

Investigators

• Principal Investigator: Lode Swinnen, MD; Johns Hopkins University

More Information

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT00809341
• Other Study ID Numbers: J0802; NA_00013656 ( Other Identifier: JHMIRB ); J0802 ( Other Identifier: SKCCCRO )
• First Posted: December 17, 2008
• Results First Posted: September 25, 2018
• Last Update Posted: September 25, 2018
• Last Verified: September 2018

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:

B-Cell; non-Hodgkin's; Lymphoma

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Prednisone; Cyclophosphamide; Ifosfamide; Rituximab; Carboplatin; Doxorubicin; Etoposide; Vincristine; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors