A Phase II Trial of Ifosfamide, Etoposide, Cytarabine, and Methotrexate (IVAM) Chemotherapy for Refractory or Relapsed Diffuse Large B Cell Lymphoma (IVAM)

A phase II trial of ifosfamide, etoposide, cytarabine, and methotrexate (IVAM) chemotherapy for refractory or relapsed diffuse large B cell lymphoma

Study Overview

• Status: Enrolling by invitation
• Conditions: Diffuse Large B Cell Lymphoma
• Intervention / Treatment: Drug: Ifosfamide, Etoposide, Cytarabine, and Methotrexate (IVAM) Chemotherapy

Detailed Description

Diffuse Large B-Cell lymphoma is currently used as a standard treatment, with a combination of chemotherapy (R-CHOP), which includes Rituximab. However, the survival rate is very poor if the primary treatment is refractory or relapsed within a year or less. The duration of these patients ' lives is around one year and the five-year survival rate is 15-20 %. Thus, a new treatment strategy is needed to improve the survival of the patient with DLBCL, which are either refractory and relapsed.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent
• Histologically confirmed adult patients diagnosed with DLBCL refractory or relapsed.
• Large scale B cell lymphoma not received ASCT(autologous stem-cell transplantation ) after primary chemotherapy

• At least one measurable lesion

  • ≥1 cm in greatest transverse diameter by spiral CT
  • ≥2 cm in greatest transverse diameter by conventional CT
  • ≥1 cm in visible skin lesion
  • ≥2 cm in digital exploration
• Performance status: Eastern Cooperative Oncology Group (ECOG) 0-2.
• Age 19~59yrs
• MUGA(multiple gated acquisition scan ): Non-Clinical significant and 2D-Echo( Cardiac Index ≥ 50 % )
• Adequate renal function: serum creatinine level < 2.0 mg/dL(177μmol/L) Adequate liver functions: Transaminase (AST/ALT) < 3 X upper limit of normal value (or < 5 x ULN in the presence of DLBCL involvement of the liver), bilirubin < 2 X upper normal value (or < 5 x upper limit of normal in the presence of DLBCL involvement of the liver)
• Adequate hematological function: hemoglobin ≥ 9.0 g/dL absolute neutrophil count (ANC) ≥ 1,500/μL and platelet count ≥ 75,000/μL,
• A negative serum or urine pregnancy test prior to treatment must be available both for pre menopausal women and for women who are < 1 years after the onset of menopause.

Exclusion Criteria:

• Pre-treatment for ASCT
• Central nervous system (CNS) involvement by lymphoma
• Prior history of malignancies other than lymphoma (except for treated Non Melanoma Skin Cancer, early gastric cancer or carcinoma in situ of the cervix or breast or untreated prostatic cancer without any plan for a treatment) unless the patient has been free of the disease for ≥ 5 years
• Pregnant or lactating woman, Childbearing potential not employing adequate contraception
• Active uncontrolled infections(Bacterial, Viral, Fungus)
• Other serious illness or medical conditions
• Other experimental drug under investigation, or concomitant chemotherapy, hormonal therapy, or immunotherapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: I Ifosfamide, Etoposide, Cytarabine, and Methotrexate (IVAM)	Drug: Ifosfamide, Etoposide, Cytarabine, and Methotrexate (IVAM) Chemotherapy; Every cycle(4weeks) Subject will receive Ifosfamide 1.5 g/m2 over 2 hours for Day1~Day5 by Intravenous infusion, Etoposide 150 mg/m2 over 3 hours on Day1~Day3 by Intravenous infusion, Cytarabine 100 mg/m2 over 1 hour on Day1~Day3 by Intravenous infusion.; Other Names: IVAM

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response	CT, PET-CT(positron emission computed tomography )	2 to 3 weeks after completion of the 2nd cycle of treatment (each cycle is 28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess response rate	CT, PET-CT	4 to 5 weeks after completion of the 4th cycle of treatment(each cycle is 28 days)
Assess response rate	CT, PET-CT	6 to 8 weeks after completion of the 6th cycle of treatment(each cycle is 28 days)
Assess response rate	CT, PET-CT	After completion of the treatment, up to 24weeks
Assess response rate	CT, PET-CT	After 1year completion of the treatment up to 1year
Assess response rate	CT, PET-CT	Afer 2years completion of the treatment up to 3years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assess overall survival	CT, PET-CT	The time from the 1st day of treatment to death of any cause or the date of last follow-up, assessed up to 66 months

Collaborators and Investigators

• Sponsor: Asan Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Anticipated): December 31, 2025
• Study Completion (Anticipated): December 31, 2025

Study Registration Dates

• First Submitted: October 30, 2017
• First Submitted That Met QC Criteria: December 22, 2017
• First Posted (Actual): December 26, 2017

Study Record Updates

• Last Update Posted (Actual): December 26, 2017
• Last Update Submitted That Met QC Criteria: December 22, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Dermatologic Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Etoposide; Ifosfamide; Cytarabine; Methotrexate
• Other Study ID Numbers: AsanMC_LMP2017-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No