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Dose Augmented Rituximab and ICE for Pts With Primary Refractory and Poor Risk Relapsed Aggressive B-Cell NHL

Primary Purpose

Lymphoma, B-cell Non-Hodgkin's Lymphoma

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

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

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring Lymphoma, ASCT, B-cell non-Hodgkin's lymphoma, Cancer, Second line therapy, ICE, Stem cell transplant

Eligibility Criteria

18 Years - 72 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Memorial Sloan-Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment

Arm Description

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.

Outcomes

Primary Outcome Measures

Improve the Overall Response Rate

assessing the response rate (CR+PR)

Secondary Outcome Measures

Full Information

NCT ID

NCT00588094

First Posted

December 26, 2007

Last Updated

October 27, 2015

Sponsor

Memorial Sloan Kettering Cancer Center

1. Study Identification

Unique Protocol Identification Number

NCT00588094

Brief Title

Dose Augmented Rituximab and ICE for Pts With Primary Refractory and Poor Risk Relapsed Aggressive B-Cell NHL

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2015

Overall Recruitment Status

Completed

Study Start Date

October 2003 (undefined)

Primary Completion Date

March 2010 (Actual)

Study Completion Date

March 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Memorial Sloan Kettering Cancer Center

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lymphoma, B-cell Non-Hodgkin's Lymphoma

Keywords

Lymphoma, ASCT, B-cell non-Hodgkin's lymphoma, Cancer, Second line therapy, ICE, Stem cell transplant

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Treatment

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

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

Other Intervention Name(s)

ASCT,Rituxan, Ifex, Paraplatin®, etoposide, Vepesid®, Mesnex®, Neupogen, Neulasta

Intervention Description

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.

Primary Outcome Measure Information:

Title

Improve the Overall Response Rate

Description

assessing the response rate (CR+PR)

Time Frame

2 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

72 Years

Accepts Healthy Volunteers

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Craig Moskowitz, MD

Organizational Affiliation

Memorial Sloan Kettering Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Memorial Sloan-Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

12. IPD Sharing Statement

Links:

URL

http://www.mskcc.org

Description

Memorial Sloan-Kettering web site

Learn more about this trial

Dose Augmented Rituximab and ICE for Pts With Primary Refractory and Poor Risk Relapsed Aggressive B-Cell NHL

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