Cilengitide (EMD 121974) in Treating Patients With Advanced Solid Tumors or Lymphoma

National Cancer Institute (NCI)

Status and phase: Completed; Phase 1

Conditions: AIDS-related Peripheral/Systemic Lymphoma; Stage IV Small Lymphocytic Lymphoma; Stage III Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Splenic Marginal Zone Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Stage III Grade 3 Follicular Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Recurrent Mantle Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Recurrent Small Lymphocytic Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Grade 2 Follicular Lymphoma; AIDS-related Primary CNS Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Stage III Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Recurrent Adult Hodgkin Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Anaplastic Large Cell Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Intraocular Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Stage IV Adult Immunoblastic Large Cell Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Mantle Cell Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Stage IV Grade 1 Follicular Lymphoma

Treatments: Drug: cilengitide

Study type: Interventional

Funder types: NIH

Identifiers

NCT00077155

CDR0000349535 (Registry Identifier)

NCI-2012-02569

UCCRC-12774A

Details and patient eligibility

About

This phase I trial is studying the side effects and best dose of EMD 121974 in treating patients with solid tumors or lymphoma. Cilengitide (EMD 121974) may stop the growth of cancer cells by stopping blood flow to the cancer

Full description

PRIMARY OBJECTIVES:

I. Determine the dose-limiting toxicity, maximum feasible dose, and recommended phase II dose of cilengitide (EMD 121974) in patients with advanced solid tumors or lymphoma.

II. Determine the safety and tolerability of this drug in these patients.

SECONDARY OBJECTIVES:

I. Determine the pharmacokinetics of this drug in these patients. II. Determine the antineoplastic activity of this drug in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive cilengitide (EMD 121974) IV continuously on weeks 1-4. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of EMD 121974 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.

Enrollment: 45 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Histologically confirmed solid tumor or lymphoma

• Refractory to standard therapy or no standard therapy exists

• Measurable or evaluable disease

• No active brain metastases

  • Previously treated brain metastases allowed provided the patient is not currently receiving corticosteroids
  • Primary brain neoplasms allowed, regardless of corticosteroid use

• Performance status - Karnofsky 70-100%

• WBC ≥ 3,000/mm^3

• Absolute neutrophil count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• No life-threatening bleeding diathesis within the past 6 months

• Bilirubin normal (unless due to Gilbert's syndrome)

• No symptomatic congestive heart failure

• No unstable angina pectoris

• No cardiac arrhythmia

• No prior proven gastric or duodenal ulcer

• No clinically significant gastrointestinal blood loss within the past 6 weeks

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No prior CNS hemorrhage

• No psychiatric illness or social situation that would preclude study compliance

• No other concurrent uncontrolled illness

• No ongoing or active infection

• No prior cilengitide (EMD 121974)

• No other concurrent biologic therapy

• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered

• No concurrent chemotherapy

• See Disease Characteristics

• More than 4 weeks since prior radiotherapy and recovered

• No concurrent palliative radiotherapy

• No other concurrent anticancer agents or therapies intended to treat the malignancy

• No other concurrent investigational agents

• No concurrent anticoagulation therapy that increases INR or aPTT above the normal range

  • Line prophylaxis allowed

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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45 participants in 1 patient group

Treatment (cilengitide)

Experimental group

Description:

Patients receive cilengitide (EMD 121974) IV continuously on weeks 1-4. Courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of EMD 121974 until the 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.

Treatment:

Drug: cilengitide