Cyclosporine in Treating Patients With Recurrent or Refractory Angioimmunoblastic T-Cell Lymphoma

A Phase II Study of Cyclosporine in the Treatment of Angioimmunoblastic T-Cell Lymphoma

RATIONALE: Cyclosporine may help the immune system slow the growth of angioimmunoblastic T-cell lymphoma.

PURPOSE: This phase II trial is studying how well cyclosporine works in treating patients with recurrent or refractory angioimmunoblastic T-cell lymphoma.

Study Overview

• Status: Terminated
• Conditions: Lymphoma
• Intervention / Treatment: Drug: cyclosporine

Detailed Description

OBJECTIVES:

Primary

• Determine the response rate (complete and partial) in patients with recurrent or refractory angioimmunoblastic T-cell lymphoma treated with cyclosporine.

Secondary

• Determine the disease-free, progression-free, and overall survival of patients treated with this drug.
• Determine the toxicity of this drug in these patients.

OUTLINE: Patients receive oral cyclosporine twice daily for up to 36 weeks in the absence of unacceptable toxicity or disease progression during weeks 1-6. Patients experiencing disease progression during weeks 7-36, receive an additional 36 weeks of therapy.

Patients are followed every 3 months for 2 years and then every 6 months for 1 year.

PROJECTED ACCRUAL: A total of 27 patients will be accrued for this study within 2.5 years.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305-5824
      • Stanford Cancer Center
  • Illinois
    • Aurora, Illinois, United States, 60504
      • Rush-Copley Cancer Care Center
    • Berwyn, Illinois, United States, 60402
      • Hematology Oncology Associates of Illinois - Berwyn
    • Chicago, Illinois, United States, 60611-3013
      • Robert H. Lurie Comprehensive Cancer Center at Northwestern University
    • Chicago, Illinois, United States, 60611
      • Hematology and Oncology Associates
    • Chicago, Illinois, United States, 60657
      • Saint Joseph Hospital
    • Joliet, Illinois, United States, 60435
      • Joliet Oncology-Hematology Associates, Limited - West
    • Joliet, Illinois, United States, 60432
      • Midwest Center for Hematology/Oncology
    • Libertyville, Illinois, United States, 60048
      • North Shore Oncology and Hematology Associates, Limited - Libertyville
    • Naperville, Illinois, United States, 60563
      • La Grange Oncology Associates - Geneva
    • Niles, Illinois, United States, 60714
      • Cancer Care and Hematology Specialists of Chicagoland - Niles
    • Skokie, Illinois, United States, 60076
      • Hematology Oncology Associates - Skokie
    • Urbana, Illinois, United States, 61801
      • Carle Cancer Center at Carle Foundation Hospital
    • Urbana, Illinois, United States, 61801
      • CCOP - Carle Cancer Center
  • Indiana
    • Michigan City, Indiana, United States, 46360
      • Saint Anthony Memorial Health Centers
  • Iowa
    • Sioux City, Iowa, United States, 51101
      • Siouxland Hematology-Oncology Associates, LLP
    • Sioux City, Iowa, United States, 51104
      • St. Luke's Regional Medical Center
    • Sioux City, Iowa, United States, 51104
      • Mercy Medical Center - Sioux City
  • Maryland
    • Baltimore, Maryland, United States, 21231-2410
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Michigan
    • Kalamazoo, Michigan, United States, 49007
      • Bronson Methodist Hospital
    • Kalamazoo, Michigan, United States, 49001
      • Borgess Medical Center
    • Kalamazoo, Michigan, United States, 49007-3731
      • West Michigan Cancer Center
  • Ohio
    • Lima, Ohio, United States, 45801
      • St. Rita's Medical Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosis of angioimmunoblastic T-cell lymphoma (recurrent or refractory) based on histologic examination.
• At least one objective measurable or evaluable disease parameter.
• Have failed at least one type of treatment: chemotherapy, auto-transplant, or steroid treatment. Patients may not receive concurrent chemotherapy.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Adequate renal function as indicated by creatinine <= 1.5 the upper limit of normal (ULN).
• Adequate liver function as indicated by alkaline phosphatase, Aspartate Aminotransferase (AST), and Alanine Aminotransferase (ALT) <= 2x the upper limit of normal.
• Total bilirubin <= 2x the upper limit of normal.
• Age 18 or older.

Exclusion Criteria:

• Prior cyclosporine or Tacrolimus (FK506).
• Prior allogeneic transplant.
• Evidence of active infection.
• Congestive heart failure, kidney failure, liver failure, or other severe co-morbidities.
• Evidence of active neurological impairment.
• Previous history of hypersensitivity to cyclosporine and/or Cremorphor EL (polyoxyethylated oil).
• History of other malignancies (other than cured carcinomas in situ of the cervix or basal cell carcinoma of the skin).
• pregnant or breastfeeding women.
• Human immunodeficiency virus (HIV) positive.

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: Cyclosporine; High dose cyclosporine weeks 1-6, then maintenance dose cyclosporine weeks 7-36. If CR, PR, or SD at week 36 evaluation, treatment is complete. If progression occurs during weeks 7-36, patients will re-register to Step 2 at time of PD and begin high dose therapy (weeks 1-6), followed by maintenance therapy (weeks 7-36). At second progression patients will end protocol treatment.

Drug: cyclosporine; Cyclosporine doses will be based on actual body weight unless actual body weight is > 15 kg higher than the ideal body weight. Cyclosporine dose will be adjusted to maintain a trough whole blood level of 250-450 ng/mL during the high dose period (weeks 1 -6, starting dose will begin at cyclosporine 3 mg/kg by mouth two times a day (PO BID)) and 150-250 ng/mL during the maintenance period (weeks 7-36, maintenance dose will begin at cyclosporine 2 mg/kg PO BID) in the absence of renal toxicity; Other Names: CSA,; Neoral,; Gengraf

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate (Complete and Partial Response)	Response was assessed based upon the criteria from the International Workshop to Standardize Criteria for Non-Hodgkin's Lymphoma. Response included complete response and partial response. Complete response was defined as complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease related B-symptoms if present prior to therapy, as well as normalization of those biochemical abnormalities definitely attributed to NHL. All lymph nodes and nodal masses must have regressed to normal size. Partial response was defined as a decrease of > 50% in the SPD (sum of the products of the diameters) of the six largest (or less) dominant nodes or nodal masses, no increase in the size of the liver or the spleen, and no new sites of disease.	Assessed at weeks 6, 12, 24 and 36 from onset of treatment, and then at 1 year, 18 months, 2 years and 3 years from registration during follow-up.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall survival was defined as time from randomization to death from any cause.	Assessed every 3 months for 2 years, then every 6 months for 1 year.

Collaborators and Investigators

• Sponsor: Eastern Cooperative Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Ranjana Advani, MD, Stanford University

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2006
• Primary Completion (Actual): March 1, 2009
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: October 3, 2003
• First Submitted That Met QC Criteria: October 6, 2003
• First Posted (Estimated): October 7, 2003

Study Record Updates

• Last Update Posted (Actual): June 29, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: angioimmunoblastic T-cell lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphadenopathy; Lymphoma; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Immunoblastic Lymphadenopathy; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins
• Other Study ID Numbers: CDR0000331864; U10CA021115 (U.S. NIH Grant/Contract); E2402 (Other Identifier: Eastern Cooperative Oncology Group (ECOG))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No