Dose Augmented Rituximab and Ice for Patients With Primary Refractory and Poor Risk Relapsed Aggressive B-Cell Non-Hodgkin's Lymphoma - Full Text View

Sponsored by:	Memorial Sloan-Kettering Cancer Center
Information provided by:	Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:	NCT00588094

Purpose

The purpose of this research is to study a treatment program for patients with aggressive lymphoma that has come back after initial or first therapy (called relapsed) or that has not responded to first therapy (called refractory). Since 1993, we have used a combination of chemotherapy known as ICE (Ifosfamide, Carboplatin, and Etoposide) for your type of lymphoma. In many patients, this treatment helps the disease to shrink before giving high-dose therapy and autologous stem cell transplant (ASCT). Only patients who respond to these types of treatments have a chance of their disease going away (remission) with an ASCT. In 1999, we studied the same treatment but added another medicine for your type of lymphoma, Rituximab (Rituxan), to the ICE treatment (RICE). More patients had lymphoma shrinkage from this treatment (chemosensitive disease) than with ICE alone. These patients then received high dose therapy and autologous stem cell transplant and have an improved chance of having a remission. ICE chemotherapy is standard chemotherapy used at Memorial Sloan-Kettering Cancer Center. However, it is different in this study because of the higher doses. We are testing higher doses of RICE treatment for patients in this study.

In our current study in Hodgkin's lymphoma, we are giving these higher doses of ICE (called augmented ICE) to patients who also have higher risk. We hope to show in this study that by using Rituximab and augmented ICE that we can improve your ability to achieve a remission (that is, to have the disease go away).

Condition	Intervention	Phase
Lymphoma B-Cell Non-Hodgkin's Lymphoma	Drug: Rituximab, Ifosfamide, Carboplatin, VP-16, Mesna, G-CSF, Stem Cell Transplant	Phase II

MedlinePlus related topics: Cancer Lymphoma

Drug Information available for: Mesna Etoposide Carboplatin Etoposide phosphate Granulocyte colony-stimulating factor Rituximab Ifosfamide

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Non-Randomized, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Phase II Study of Dose Augmented Rituximab and Ice for Patients With Primary Refractory and Poor Risk Relapsed Aggressive B-Cell Non-Hodgkin's Lymphoma Undergoing Second-Line Therapy Prior to Stem Cell Transplantation

Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:

To assess the ability R-ICEesc chemotherapy to improve the overall response rate in primary refractory or poor risk relapsed aggressive B cell lymphoma patients from 50% to 70% [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To assess the ability of RICEesc to effectively mobilize PBPCs; To assess the hematologic and non-hematologic toxicity of the treatment program [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Enrollment:	20
Study Start Date:	October 2003
Estimated Study Completion Date:	October 2010
Estimated Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Treatment: Experimental R-ICEesc will be administered with the intent of administering 2 cycles, each 21 days apart admixed with 4 doses of rituximab. G-CSF will be administered at 960 ug or 10 ug/kg if patient is > 100 kg after cycles one and two for PBPC collection for the first 10 patients enrolled. G-CSF will be administered in standard dosing for cycle one and then at 960 ug or 10 ug/kg (if patient is > 100 kg) after cycle two for PBPC collection for the remaining 22 patients. All responding patients who make at least 2 x 106 CD34+ cells/kg will receive high dose therapy and ASCT on other protocols.	Drug: Rituximab, Ifosfamide, Carboplatin, VP-16, Mesna, G-CSF, Stem Cell Transplant ANC must be ≥1000/µl and platelet count must be ≥50,000/µl. Rituximab will be administered at a dose of 375 mg/m2 IV on days 1 and 3 of the each cycle. Premedication will be given.ICE will be administered as follows: Day 3: Etoposide 200 mg/m2 IV q12 hrs x 3. Day 4: Ifosfamide 10 g/m2 and MESNA 10 g/m2 mixed and infused together as a continuous infusion over 48 hours. Day 5: Carboplatin IV dosed by the Calvert formula using an AUC of 5. Carboplatin dose (mg) = 5 x (Clcr + 25) For the first ten patients enrolled, G CSF will be administered beginning on day seven of each cycle and G CSF will continue until stem cell collection is completed. The dose will be 960 ug or 10 ug/kg if weight is greater than 100 kg. For the remaining patients, G-CSF will be administered for 10 days beginning on day 7 for cycle 1. The dose will be 300-480 ug/d. For cycle 2 the dose will be 960 ug or 10ug/kg if weight is > 100kg. Leukapheresis will continue.

Arms

Assigned Interventions

Treatment: Experimental

R-ICEesc will be administered with the intent of administering 2 cycles, each 21 days apart admixed with 4 doses of rituximab. G-CSF will be administered at 960 ug or 10 ug/kg if patient is > 100 kg after cycles one and two for PBPC collection for the first 10 patients enrolled. G-CSF will be administered in standard dosing for cycle one and then at 960 ug or 10 ug/kg (if patient is > 100 kg) after cycle two for PBPC collection for the remaining 22 patients. All responding patients who make at least 2 x 106 CD34+ cells/kg will receive high dose therapy and ASCT on other protocols.

Drug: Rituximab, Ifosfamide, Carboplatin, VP-16, Mesna, G-CSF, Stem Cell Transplant

ANC must be ≥1000/µl and platelet count must be ≥50,000/µl. Rituximab will be administered at a dose of 375 mg/m2 IV on days 1 and 3 of the each cycle.

Premedication will be given.ICE will be administered as follows: Day 3: Etoposide 200 mg/m2 IV q12 hrs x 3. Day 4: Ifosfamide 10 g/m2 and MESNA 10 g/m2 mixed and infused together as a continuous infusion over 48 hours. Day 5: Carboplatin IV dosed by the Calvert formula using an AUC of 5.

Carboplatin dose (mg) = 5 x (Clcr + 25) For the first ten patients enrolled, G CSF will be administered beginning on day seven of each cycle and G CSF will continue until stem cell collection is completed. The dose will be 960 ug or 10 ug/kg if weight is greater than 100 kg. For the remaining patients, G-CSF will be administered for 10 days beginning on day 7 for cycle 1. The dose will be 300-480 ug/d. For cycle 2 the dose will be 960 ug or 10ug/kg if weight is > 100kg. Leukapheresis will continue.

Detailed Description:

The purpose of this study is to determine if dose escalation of the rituximab-ICE (RICEesc) program can improve the overall response rate of patients with primary refractory or poor risk relapsed aggressive B cell lymphoma. R-ICEesc will be administered for 2 cycles with peripheral blood progenitor cells (PBPCs) collected after cycle 2.

A two-stage design will be employed, such that the study will be terminated if in the first cohort of patients it appears that the overall response rate is <50% or if >25% patients fail to mobilize at least 2 x 106 CD34+ cells/kg.

Eligibility

Ages Eligible for Study:	18 Years to 72 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Histologic diagnosis of the one of the following B cell aggressive lymphomas, confirmed by an MSKCC pathologist: Diffuse Large, Immunoblastic, Mantle cell, Anaplastic Large Cell, De novo transformation of follicular lymphoma, or classical Hodgkin's lymphoma which is CD20 antigen positive.
Tumors must stain positive for CD20.
Primary refractory disease proven by biopsy or fine needle aspiration (cytology) of an involved site
Relapsed diffuse large, immunoblastic, anaplastic, de novo transformation of follicular lymphoma, or classical Hodgkin's lymphoma which is CD20 antigen positive proven by biopsy or fine needle aspiration (cytology) of an involved field site and at least two of the three following risk factors: LDH> upper limit of normal, KPS < 80%, Stage III or IV disease.
All mantle cell lymphoma patients in first relapse
Failure of doxorubicin or mitoxantrone containing front-line therapy
Bidimensionally measurable disease.
Cardiac ejection fraction of greater than 50%, measured since last chemotherapy.
Serum creatinine <1.5 mg/dl; if creatinine >1.5 mg/dl then the measured 12- or 24-hour creatinine clearance must be >60 ml/minute.
ANC>1000/µl and Platelets>50,000/µl
Total bilirubin < 2.0 mg/dl in the absence of a history of Gilbert's disease.
Females of childbearing age must be on an acceptable form of birth control.
Age between 18 and 72
HIV I and II negative.
Patients or their guardians must be capable of providing informed consent.

Exclusion Criteria:

Any lymphoma subtype other than those described among the inclusion criteria.
All patients with relapsed diffuse large, immunoblastic, anaplastic, de novo transformation of follicular lymphoma, or classical Hodgkin's lymphoma which is CD20 antigen positive disease who have <2 of following risk factors: LDH> upper limit of normal, KPS < 80%, Stage III or IV disease.
History of second-line chemotherapy
Presence of CNS involvement.
Prior treatment with carboplatin, cisplatin, ifosfamide, or etoposide
Hepatitis B surface antigen positive.
Known pregnancy or breast-feeding.
Medical illness unrelated to NHL, which in the opinion of the attending physician and/or principal investigator will preclude administering chemotherapy safely.
History of any malignancy for which the disease-free interval is <5 years, excluding curatively treated cutaneous basal cell or squamous cell carcinoma and carcinoma in-situ of the cervix

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00588094

Locations

United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065

Sponsors and Collaborators

Memorial Sloan-Kettering Cancer Center

Investigators

Principal Investigator:

Craig Moskowitz, MD

Memorial Sloan-Kettering Cancer Center

More Information

Additional Information:

Memorial Sloan-Kettering web site This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Memorial Sloan-Kettering Cancer Center ( Craig Moskowitz, MD )
Study ID Numbers:	03-075
Study First Received:	December 26, 2007
Last Updated:	March 17, 2009
ClinicalTrials.gov Identifier:	NCT00588094 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Memorial Sloan-Kettering Cancer Center:

Lymphoma
ASCT
B-cell non-Hodgkin's lymphoma
Cancer

Second line therapy
ICE
Stem cell transplant

Study placed in the following topic categories:

Immunoproliferative Disorders
Immunologic Factors
Rituximab
Carboplatin
Etoposide phosphate
Lymphoma, B-Cell
Lymphoma, Small Cleaved-cell, Diffuse
Lymphatic Diseases
Ifosfamide
B-cell Lymphomas

Antineoplastic Agents, Alkylating
Antirheumatic Agents
Lymphoma, Non-Hodgkin
Aggression
Lymphoproliferative Disorders
Alkylating Agents
Mesna
Lymphoma
Etoposide
Isophosphamide mustard

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Immunoproliferative Disorders
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Antineoplastic Agents
Rituximab
Physiological Effects of Drugs
Carboplatin
Pharmacologic Actions
Lymphoma, B-Cell

Lymphatic Diseases
Neoplasms
Ifosfamide
Therapeutic Uses
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Alkylating Agents
Lymphoma

ClinicalTrials.gov processed this record on May 07, 2009