Gemcitabine Hydrochloride, Carboplatin, Dexamethasone, and Rituximab in Treating Patients With Previously Treated Lymphoid Malignancies

Study Overview
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Brief Summary
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This pilot phase II trial studies the side effects and how well giving gemcitabine hydrochloride, carboplatin, dexamethasone, and rituximab together works in treating patients with previously treated lymphoid malignancies. Drugs used in chemotherapy, such as gemcitabine hydrochloride, carboplatin, and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Giving more than one drug (combination chemotherapy) and giving monoclonal antibody therapy with chemotherapy may kill more cancer cells

Detailed Description
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OBJECTIVES: I. To determine the feasibility and safety of Gemcitabine/Carboplatin/Dexamethasone with or without Rituximab in previously treated lymphoid malignancies (rituximab will only be evaluated in CD20 positive malignancies). II. To determine the efficacy of the above regimen. III. To determine the ability to proceed to blood stem peripheral blood collection following the above regimens (the impact of above regimen on stem cell reserve). IV. To determine remission duration. All patients are treated with gemcitbine, carboplatin, and dexamethasone. Patients with CD20 + lymphomas also receive rituximab. After completion of study treatment, patients are followed up at 3-4 weeks and then every 6 months for 5 years.

Official Title
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A Phase II Study Evaluating the Efficacy of Gemcitabine, Carboplatin, and Dexamethasone and Rituximab for Previously Treated Lymphoid Malignancies

Conditions
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Adult Nasal Type Extranodal NK/T-cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Cutaneous B-cell Non-Hodgkin Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Hepatosplenic T-cell Lymphoma, Intraocular Lymphoma, Nodal Marginal Zone B-cell Lymphoma, Noncutaneous Extranodal Lymphoma, Peripheral T-cell Lymphoma, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Adult T-cell Leukemia/Lymphoma, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, Recurrent Small Lymphocytic Lymphoma, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, Testicular Lymphoma, Waldenstrom Macroglobulinemia

Intervention / Treatment
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* Drug: gemcitabine hydrochloride
* Drug: carboplatin
* Drug: dexamethasone
* Biological: rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have relapsed or primary refractory lymphoid malignancy (including B-cell, T-cell, or Hodgkin's Disease) Revised European American classification (REAL), or World Health Organization (WHO) classification of patients malignancies must be provided Patients must have measurable disease defined as lesions that can be accurately measured in two dimensions by computed tomography (CT), magnetic resonance imaging (MRI), medical photograph (skin or oral lesion), plain x-ray, or other conventional technique and a greatest transverse diameter of 1 cm or greater; or palpable lesions with both diameters >= 2 cm; Note: CT scans remain the standard for evaluation of nodal disease Patients must have a bone marrow aspirate and biopsy within 28 days of enrollment and no intervening anticancer therapy Patients must have a CT of chest, abdomen, and pelvis within 28 days of enrollment; patients with evidence of adenopathy in the neck must have a CT of neck Patients should not have evidence active central nervous system lymphoma Patients must have a Southwest Oncology Group (SWOG) performance status of 0, 1, or 2 Patients should have absolute neutrophil count (ANC) >= 1,500/uL; exception: patients with cytopenia thought to be due to disease in their bone marrow, that do not meet this criteria, may be enrolled on the protocol at the Study Chair's discretion Patients should have platelets >= 100,000/uL; exception: patients with cytopenia thought to be due to disease in their bone marrow, that do not meet this criteria, may be enrolled on the protocol at the Study Chair's discretion Serum bilirubin less than 2 times the upper limit of normal Serum creatinine less than 1.5 times the upper limit of normal and creatinine clearance greater than 50/ mL per minute Patients must have serum lactate dehydrogenase (LDH) performed within 14 days prior to treatment All patients must be informed of the investigational nature of this study and have given written consent in accordance with institutional and federal guidelines Must anticipate that patient will complete at least 2 cycles of chemotherapy Exclusion Criteria: Patients known to be human immunodeficiency virus (HIV) positive Pregnant or nursing women; men or women of reproductive potential may not participate unless they have agreed to use an effective contraceptive method Patients with other prior malignancies except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, cervical cancer in situ, or other cancer from which the patient has been disease-free for 5 years or greater unless approved by the Principal Investigator (PI) Patients that are refractory (i.e., not responded or progressed within 6 months) to a carboplatin or cisplatin-based regimen or a gemcitabine-based regimen Patients with active hepatitis B virus (HBV) infection or hepatitis Patients that have other medical conditions that would contraindicate treatment with aggressive chemotherapy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on days 1 and 8, carboplatin IV over 30-60 minutes on day 1, and dexamethasone orally (PO) on days 1-4. Treatment repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Patients with CD20-POSITIVE LYMPHOMAS also receive rituximab IV on day 8. | Drug: gemcitabine hydrochloride<br>* Given IV<br>* Other names: Gemzar;Drug: carboplatin<br>* Given IV<br>* Other names: Paraplatin;Drug: dexamethasone<br>* Given PO<br>* Other names: DXM;Biological: rituximab<br>* Given IV in CD20-POSITIVE LYMPHOMAS cases<br>* Other names: Rituxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ability to Successfully Deliver the Investigational Therapy Without Incurring the Protocol Suspension Rules | Count of participants that received the investigational therapy without incurring the protocol suspension rules. A stopping rule for safety was employed such that the study would be suspended if sufficient evidence indicated that the true grade 4-5 non-hematologic toxicity rate exceeded 10%. | At 3-4 weeks after completion of study treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall and Complete Response Rates | Response was assessed per standard criteria (Cheson BD, Horning SJ, Coiffier B, et al. Report of an international workshop to standardize response criteria fornon-Hodgkin's lymphomas. J Clin Oncol 1999;17:1244-1253.) | 3-4 weeks after completion of study treatment | 
| Hematologic and Non-hematologic Adverse Events. | Count of participants with grade 3/4 hematologic and non-hematologic adverse events. | 3-4 weeks after completion of study treatment | 
| Peripheral Blood Stem Cell Collection | Count of patients that attempted and had successful autologous peripheral blood stem cell (PBSC) collection. | Up to 12 weeks |