Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Published Results
Trial Contact Information
Related Information
Registry Information

Alternate Title

Siplizumab in Treating Patients With Lymphoproliferative Disorder

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase I	Treatment	Closed	18 and over	NCI, Pharmaceutical / Industry	NCI-04-C-0031 MEDIMMUNE-MI-CP094, NCT00075361

Objectives

Primary

1. Determine the maximum tolerated dose of siplizumab (MEDI-507) in patients with CD2-positive lymphoproliferative disorders.
2. Determine the safety and tolerability of this drug in these patients.

Secondary

1. Determine the time to MEDI-507 saturation of CD2-binding sites in peripheral blood and tumor aspirates of these patients.
2. Determine the serum pharmacokinetics of this drug in these patients.
3. Determine the time to T-cell and natural killer cell depletion and recovery in patients after treatment with this drug.
4. Determine the antitumor activity of this drug, in terms of response rate, time to progression, and overall survival, in these patients.

Entry Criteria

Disease Characteristics:

• Histologically confirmed lymphoproliferative disorder, including the following types:
  • Adult T-cell leukemia
    • No smoldering leukemia
  • Cutaneous T-cell lymphoma
    • All stages, excluding stage Ia
    • Patients with stage Ib, II, or III disease must have failed at least 1 prior standard therapy regimen
  • Peripheral T-cell lymphoma
    • Stage I-IV
    • Disease progression after standard chemotherapy
  • Large granular lymphocyte leukemia meeting the following criteria:
    • Must have 1 of the following:
      • Myelosuppression based on at least 1 of the following laboratory values:
        • Granulocyte count no greater than 1,500/mm³
        • Platelet count no greater than 75,000/mm³
        • Hemoglobin no greater than 10 g/dL
      • Requirement for hematopoietic support (e.g., transfusion or colony-stimulating factors, including filgrastim [G-CSF], interleukin-11, or epoetin alfa) to maintain blood levels or control systemic symptoms (e.g., fever, night sweats, or weight loss)
    • Disease unresponsive to 1 prior therapy regimen
    • Monoclonal and polyclonal forms of disease allowed



• CD2-positive by immunohistochemistry
  • At least 30% of tumor cells must express CD2



• Measurable or evaluable disease



• No history of CNS disease

Prior/Concurrent Therapy:

Biologic therapy

• At least 30 days since prior monoclonal antibody therapy
• No prior siplizumab (MEDI-507)
• No other concurrent monoclonal antibody therapies
• No other concurrent biologic response modifier therapy
• No concurrent gamma globulin
• Concurrent G-CSF, epoetin alfa, and interleukin-11 allowed for large granular lymphocyte leukemia

Chemotherapy

• See Disease Characteristics
• At least 3 weeks since prior cytotoxic chemotherapy and recovered
• No concurrent FDA-approved or investigational cancer chemotherapeutic agents

Endocrine therapy

• At least 3 weeks since prior prolonged cytolytic steroid therapy and recovered
• No concurrent steroids

Radiotherapy

• Not specified

Surgery

• At least 3 weeks since prior surgery and recovered

Other

• At least 30 days since other prior investigational anticancer drugs
• No other concurrent investigational anticancer drugs

Patient Characteristics:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• More than 2 months

Hematopoietic

• See Disease Characteristics
• Granulocyte count at least 1,000/mm³*
• Platelet count at least 50,000/mm³*

 [Note: *Requirement waived for patients with large granular lymphocyte leukemia]

Hepatic

• SGOT and SGPT ≤ 2.0 times upper limit of normal (ULN) (5 times ULN for patients with Gilbert's syndrome)
• Bilirubin ≤ 2.0 mg/dL (3.5 times ULN for patients with Gilbert's syndrome)
• Hepatitis B surface antigen negative
• No positive antibodies to hepatitis C virus

Renal

• Creatinine ≤ 1.5 mg/dL

  OR

• Creatinine clearance > 60 mL/ min by 24-hour urine collection

Cardiovascular

• No myocardial infarction within the past 6 months
• No uncontrolled hypertension within the past 6 months
• No stroke or transient ischemic attack within the past 6 months

Pulmonary

• Oxygen saturation level at least 90% by pulse oximetry
• No respiratory insufficiency requiring oxygen therapy

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative
• Symptomatic cytomegalovirus (CMV) negative or CMV PCR ≤ 1000 copies
• No history of significant adverse events related to previously administered monoclonal antibody
• No active infection requiring systemic anti-infective therapy
• No physical or general medical illness that would increase risk to the patient
• No psychological or behavioral condition that would increase risk to the patient or preclude study participation

Expected Enrollment

A total of 88 patients will be accrued for this study.

Outcomes

Safety and maximum tolerated dose at study completion then every 3 months for 1 year

Outline

This is an open-label, dose-escalation study.

Patients receive siplizumab (MEDI-507) IV over 4 hours on days 1 and 2 every 2 weeks for 16 weeks OR on days 1-3 every 2 weeks for 16 weeks OR on days 1 and 14, then weekly for 16 weeks in the absence of disease progression or unacceptable toxicity. Patients with a positive treatment response (e.g., stable disease, minor response, partial response, or complete response) after 16 weeks of treatment may continue to receive MEDI-507 as above in the absence of disease progression or unaccebtable toxicity.

Cohorts of 3-6 patients receive escalating doses of MEDI-507 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

After completion of treatment, patients are followed at 30 days and then every 3 months for 1 year.

Janik JE, Morris JC, Stetler-Stevenson M, et al.: Phase I trial of siplizumab in CD2-positive lymphoproliferative disease. [Abstract] J Clin Oncol 23 (Suppl 16): A-2533, 174s, 2005.

Trial Contact Information

Trial Lead Organizations

NCI - Center for Cancer Research

John Janik, MD, Principal investigator		Ph: 301-402-2913 Email: janikj@mail.nih.gov

Related Information

Featured trial article

Registry Information
Official Title		Phase I Trial Of Medi-507 In CD2-Positive Lymphoproliferative Disease
Trial Start Date		2003-11-10
Registered in ClinicalTrials.gov		NCT00075361
Date Submitted to PDQ		2003-11-10
Information Last Verified		2007-04-29

Back to Top