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Evaluation of the Safety and Efficacy of Nipent, Cytoxan, and Rituxan

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Astex Pharmaceuticals
Pharmatech
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00496873
First received: July 3, 2007
Last updated: September 23, 2014
Last verified: September 2014
  Purpose

Primary Objective:

To determine the objective response rate, following treatment with pentostatin, rituximab, and cyclophosphamide, of patients with zero or one prior treatment regimen for stage III or IV, low-grade B-cell non-Hodgkin's lymphoma (NHL) or bulky lymphoma.

Secondary Objectives:

  1. To determine the duration of response, time to progression, and time to treatment failure of patients with previously untreated or first line treated NHL
  2. To evaluate the toxicity of combination pentostatin, rituximab, and cyclophosphamide therapy
  3. To evaluate the incidence and severity of adverse events graded according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0
  4. To correlate disease response of SLL/CLL with tumor ZAP70 expression and immunoglobulin heavy chain mutations.

Condition Intervention Phase
Lymphoma
Drug: Cytoxan
Drug: Nipent
Drug: Rituxan
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single-Center, Open-Label Study to Evaluate the Safety and Efficacy of Nipent, Cytoxan, and Rituxan ("PCR") in the Treatment of Previously Untreated and Treated, Stage III or IV, Low-Grade B-Cell Non-Hodgkin's Lymphoma or Bulky Lymphoma

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Patient Objective Response Rate (OR=CR+PR) [ Time Frame: Evaluated after treatment in Cycles 3, 6 and 9 (1 Cycle = 21 Days). ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 100
Study Start Date: June 2005
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cytoxan + Rituxan + Nipent
Cytoxan 600 mg/m^2 on Day 1 of 21-day cycle. Rituxan 375 mg/m^2 on Day 1 of 21 Day Cycle. Nipent 4 mg/m^2 on Day 1 of 21 Day Cycle.
Drug: Cytoxan
600 mg/m^2 on Day 1 of 21-day cycle.
Other Names:
  • Cyclophosphamide
  • Neosar
Drug: Nipent
4 mg/m^2 on Day 1 of 21 Day Cycle.
Other Names:
  • Pentostatin
  • Deoxycoformycin
  • DCF
Drug: Rituxan
375 mg/m^2 on Day 1 of 21 Day Cycle.
Other Name: Rituximab

Detailed Description:

All of the drugs [Cytoxan (cyclophosphamide), Rituxan (rituximab) and Nipent (pentostatin)] in this study are commonly used in the treatment of this cancer. However, using these drugs in combination is investigational.

Before you can start treatment on this study, you will have what are called "screening tests". These tests will help the doctor decide if you are eligible to take part in the study. You will have a complete medical history and physical exam. You will have blood collected (around 2-3 tablespoons) for routine tests. You will have a chest x-ray and CT scans of the chest, abdomen (stomach), and pelvis (waist area). Tumors will be measured using x-rays. You will have a sample of bone marrow collected. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle. If your doctor feels it is necessary, you may also have lymph node biopsy samples taken for special tests. Women who are able to have children must have a negative blood or urine pregnancy test.

During treatment you will be given a combination of three drugs in a 21 day (3 weeks) cycle. All drugs will be given through a needle in a vein over 4-6 hours. You will receive pentostatin first, then rituximab, and lastly cyclophosphamide. For each treatment cycle cyclophosphamide, rituximab, and pentostatin will be given on Day 1, followed by 20 days of rest.

During treatment, you will have around 2-3 tablespoons of blood collected at least once a week for routine tests. You will also provide a urine sample for routine urine tests. Depending on how the disease responds, treatment may be stopped after 3, 6, or 9 cycles. You will be taken off treatment if your disease gets worse. If your treatment is delayed for more than 2 weeks due to any side effect related to the treatment or for more than 3 weeks for any reason, you will be taken off of this study. If your doctor feels that you are having serious or intolerable side effects that are not improved by standard supportive care methods (such as medicine to control nausea or a transfusion to treat anemia) you will be taken off of this study.

After Cycles 3, 6, and 9, tumors will be measured using x-rays or other scans (CT or MRI). Bone marrow samples will be taken if they are needed to find out if the drug combination is working to control your disease.

The maximum number of cycles that you can receive is 9. If you wish to continue using this drug treatment, and it is beneficial to do so, you may continue to receive these drugs. However, these drugs are commercially available, so you will be financially responsible for the cost of these drugs.

After you receive the last cycle of chemotherapy, your doctor will decide your schedule of follow-up exams. You will have follow-up exams every 3 months for one year, every 6 months for 2nd year, then once after 1 year. During these exams, you will have a chest x-ray and CT scans of the chest, abdomen (stomach), and pelvis (waist area). You will also have blood collected (2-3 tablespoons) for routine tests.

This is an investigational study. All of the study drugs are approved by the FDA for cancer treatment and are commercially available. However, the use of the drugs in combination is investigational. Up to 100 patients will take part in this study. All enrolled will be at M. D. Anderson.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically or cytologically proven, stage III or IV, low-grade B-cell NHL, as defined by the updated WHO modification of the REAL classification for peripheral B-cell neoplasms: B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma; Lymphoplasmacytic lymphoma/immunocytoma; Follicular lymphoma; Extranodal marginal zone B-cell lymphoma of MALT type; Nodal marginal zone B-cell lymphoma (+/- monocytoid B-cells); Lymphoma with primarily bone marrow-only disease are considered eligible
  2. Bulky lymphoma or Stage II disease requiring chemotherapy will be considered for enrollment with documented Sponsor Investigator approval prior to registration.
  3. CT or MRI scans confirming measurable tumor size (lymph node must be >1cm in its longest transverse diameter). Measurement by physical exam is acceptable in the case of palpable and reproducibly measurable axillary or other superficial tumors.
  4. Positive expression of CD20 by biopsy or circulating lymphocytes.
  5. Zero or one prior chemotherapeutic or immunotherapeutic treatment regimen for B-cell NHL.
  6. Male or female greater than or equal to 18 years of age.
  7. ECOG performance status of 0-2.
  8. Adequate renal function: Creatinine less than 1.5 mg/dL; BUN less than 30 mg/dL or a creatinine clearance greater than or equal to 60 mL/min based on calculation of creatinine clearance using the Cockcroft-Gault method or from a 24-hour urine collection. Creatinine clearance 40- 59 mL/min from a 24-hour urine collection would require a Nipent dose reduction of 25%. Patients with a Creatinine clearance <40 mL/min from a 24-hour urine collection will be excluded.
  9. Adequate bone marrow function: ANC greater than or equal to 1,000 cells/µL; Platelet count greater than or equal to 75,000 cells/µL; Hemoglobin greater than or equal to 9 g/dL. Patients with idiopathic thrombocytopenia or autoimmune hemolytic anemia are eligible with prior approval of Sponsor Investigator.
  10. Adequate liver function: Bilirubin less than or equal to 2.0 mg/dL; AST and ALT less than or equal to 5 times ULN.
  11. Adequate cardiac function in the judgment of the Investigator, including NYHA classification of I or II.
  12. Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration.
  13. Patient agrees to use an acceptable method of birth control, if fertile patient (male or female), to avoid pregnancy for the duration of the study and for at least 3 months thereafter.
  14. Completed Patient Informed Consent Form.

Exclusion Criteria:

  1. Previous or current intermediate or high-grade lymphoma.
  2. WBC greater than 30,000 cells/µL.
  3. Received prior therapy using Rituxan, unless such therapy was completed at least 6 months prior to study registration. Patients whose disease was non-responsive to prior Rituxan therapy will be excluded.
  4. Known sensitivity to Nipent, Rituxan, Cytoxan or any component of these drugs.
  5. Patient received replacement steroid therapy less than 4 weeks prior to study registration.
  6. History of other malignancy that could affect the diagnosis or assessment of the study treatment.
  7. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) illness.
  8. Known prior history of and/or active viral hepatitis (HBV or HCV).
  9. Patient is unable to comply with the requirements of this study.
  10. Patients with Richter's transformation will be excluded.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00496873

Locations
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Astex Pharmaceuticals
Pharmatech
Investigators
Principal Investigator: Felipe Samaniego, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00496873     History of Changes
Other Study ID Numbers: 2004-0818, NCI-2010-00635
Study First Received: July 3, 2007
Last Updated: September 23, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Non-Hodgkin's Lymphoma
NHL
Lymphoma
B-cell chronic lymphocytic leukemia
SLL
Small Lymphocytic Lymphoma
Lymphoplasmacytic lymphoma/immunocytoma
Follicular lymphoma
Extranodal marginal zone B-cell lymphoma of MALT type
Nodal marginal zone B-cell lymphoma
Chronic Lymphocytic Leukemia
CLL
Bulky Lymphoma
Nipent
Cytoxan
Rituxan
Cyclophosphamide
Rituximab
Pentostatin

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Pentostatin
Rituximab
Adenosine Deaminase Inhibitors
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014