Rituximab, Combination Chemotherapy, Filgrastim (G-CSF), and Plerixafor in Treating Patients With Non-Hodgkin Lymphoma Undergoing Mobilization of Autologous Peripheral Blood Stem Cells

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01097057
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 20
• Location: 1
• Arm: 1
• Actual Duration (Months): 85.6
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This phase II trial is studying how well giving rituximab; ifosfamide, carboplatin, and etoposide (ICE) combination chemotherapy; and filgrastim (G-CSF) together with plerixafor works in treating patients with non-Hodgkin lymphoma undergoing mobilization of autologous peripheral blood stem cells. Giving chemotherapy (ICE) with monoclonal antibodies, such as rituximab, stops the growth of cancer cells by stopping them from dividing or by killing them and helps get better autologous stem cell product. Giving colony-stimulating factors, such as G-CSF, and plerixafor helps stem cells move from the patient's bone marrow to the blood so they can be collected and stored for future autologous transplant.

Condition or Disease	Intervention/Treatment	Phase
Non-Hodgkin Lymphoma	Drug: Carboplatin; Drug: Etoposide; Biological: Filgrastim; Drug: Ifosfamide; Procedure: Leukapheresis; Drug: Plerixafor; Biological: Rituximab	Phase 2

Detailed Description

OBJECTIVES:

1. Evaluate the efficacy of combining RICE (rituximab-ifosfamide-carboplatin-etoposide regimen [R-ICE regimen]), G-CSF, and plerixafor to collect autologous peripheral blood stem cell (PBSC) for non-Hodgkin's lymphoma (NHL) patients by: the number of days of apheresis required to reach >= 5 x 10^{6 cluster of differentiation (CD)34 cells/kg and by the total number of CD34 cells/kg collected in a maximum of 4 days if >= 5 x 10}6 CD34 cells/kg is not obtained.

OUTLINE:

Patients receive rituximab intravenously (IV) on day 1, etoposide IV on days 2-4, carboplatin IV on day 3, and ifosfamide IV on day 3 over 24 hours. Patients also receive filgrastim subcutaneously (SC) once daily beginning on day 6 and continuing until apheresis is completed and plerixafor SC once daily for up to 4 days beginning 24 hours after recovery from nadir and continuing until apheresis is completed. Patients may undergo up to 4 apheresis procedures until the optimal number of CD34+ cells are collected.

After completion of study treatment, patients are followed up at 30 days and then periodically for up to 12 months.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Mobilization of Autologous Peripheral Blood Stem Cells (PBSC) in CD20+ Lymphoma Patients Using RICE, G-CSF (Granulocyte-Colony Stimulating Factor), and Plerixafor
• Actual Study Start Date: Nov 9, 2010
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Dec 26, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (rituximab, etoposide, carboplatin, ifosfamide) Patients receive rituximab IV on day 1, etoposide IV on days 2-4, carboplatin IV on day 3, and ifosfamide IV on day 3 over 24 hours. Patients also receive G-CSF SC once daily beginning on day 6 and continuing until apheresis is completed and plerixafor SC once daily for up to 4 days beginning 24 hours after recovery from nadir and continuing until apheresis is completed. Patients may undergo up to 4 apheresis procedures until the optimal number of CD34+ cells are collected.

Drug: Carboplatin; Given IV; Other Names: Blastocarb Carboplat Carboplatin Hexal Carboplatino Carbosin Carbosol Carbotec CBDCA Displata Ercar JM-8 Nealorin Novoplatinum Paraplat Paraplatin Paraplatin AQ Paraplatine Platinwas Ribocarbo ; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16-213 VP-16 VP-16-213 ; Biological: Filgrastim; Given SC; Other Names: Filgrastim XM02 G-CSF Neupogen r-metHuG-CSF Recombinant Methionyl Human Granulocyte Colony Stimulating Factor rG-CSF Tbo-filgrastim Tevagrastim ; Drug: Ifosfamide; Given IV; Other Names: Asta Z 4942 Asta Z-4942 Cyfos Holoxan Holoxane Ifex IFO IFO-Cell Ifolem Ifomida Ifomide Ifosfamidum Ifoxan IFX Iphosphamid Iphosphamide Iso-Endoxan Isoendoxan Isophosphamide Mitoxana MJF 9325 MJF-9325 Naxamide Seromida Tronoxal Z 4942 Z-4942 ; Procedure: Leukapheresis; Given through catheter; Other Names: Leukocytopheresis Therapeutic Leukopheresis ; Drug: Plerixafor; Given SC; Other Names: AMD 3100 JM-3100 Mozobil SDZ SID 791 ; Biological: Rituximab; Given IV; Other Names: BI 695500 C2B8 Monoclonal Antibody Chimeric Anti-CD20 Antibody IDEC-102 IDEC-C2B8 IDEC-C2B8 Monoclonal Antibody MabThera Monoclonal Antibody IDEC-C2B8 PF-05280586 Rituxan Rituximab Biosimilar BI 695500 Rituximab Biosimilar PF-05280586 Rituximab Biosimilar RTXM83 RTXM83

Outcome Measures

Primary Outcome Measures

1. Number of Patients to Mobilize ≥5 x 10^6 CD34 Cells/kg Autologous PBSC (Efficacy) [One Month]

   Number of patients who achieved ≥5 x 10^6 CD34 cells/kg autologous PBSC collection by apheresis.

2. Number of Patients Who Achieved ≥5 x 10^6 CD34 Cells/kg in ≤4 Apheresis Days [Up to Four Apheresis Days]

   Number of patients to collect at least 5 x 10^6 CD34 cells/kg in under 4 apheresis procedures.

3. Number of Participants Requiring One or Two Apheresis Collection Days to Reach ≥5 x 10^6 CD34 Cells/kg [Up to Four Apheresis Days]

   Number of participants requiring one or two apheresis collection days to reach collection goal.

4. Total Number of Participants Who Did Not Collect ≥5 x 10^6 CD34 Cells/kg in a Maximum of Four Apheresis Days [Up to Four Apheresis Days]

   Number of participants who did not collect ≥5 x 10^6 CD34 cells/kg in up to four apheresis days

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of CD20+ non-Hodgkin's lymphoma

• Left ventricular ejection fraction at rest >= 50% demonstrated by multi gated acquisition scan (MUGA) or echocardiogram

• Bilirubin =< 2.0 mg/dL (except for isolated hyperbilirubinemia attributed to Gilbert syndrome)

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 3 times the upper limit of normal

• Creatinine clearance (calculated creatinine clearance is permitted) > 50 mL/min

• Signed informed consent

• Planned autologous transplant within 3 months after collection of peripheral blood stem cells (PBSCs)

Exclusion Criteria:

• Karnofsky performance score < 70%

• Uncontrolled bacterial, viral, or fungal infection (currently taking medication and with progression or no clinical improvement)

• Prior other malignancies except resected basal cell carcinoma or treated cervical carcinoma or breast cancer in situ; cancer treated with curative intent > 5 years previously will be allowed

• Pregnant or breastfeeding

• Fertile men or women unwilling to use contraceptive techniques from the time of chemo-mobilization

• Prior autologous or allogeneic hematopoietic stem cell transplant (HSCT)

• Human immunodeficiency virus (HIV) positive

• Plan to be treated on another investigational therapy within 4 weeks of enrolling on this study

• Hepatitis B carriers

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Fred Hutchinson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Leona Holmberg, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Leona Holmberg, Principal Investigator, Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT01097057
• Other Study ID Numbers: 2310.00; NCI-2009-01562; 2310.00; P30CA015704
• First Posted: Apr 1, 2010
• Last Update Posted: Jan 23, 2018
• Last Verified: Dec 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Plerixafor; Rituximab; Antineoplastic Agents, Immunological; Carboplatin; Etoposide; Etoposide phosphate; Ifosfamide; Isophosphamide mustard; Podophyllotoxin; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Lenograstim

Study Results

Participant Flow

Arm/Group Title	Treatment (Rituximab, Etoposide, Carboplatin, Ifosfamide)
Arm/Group Description	Patients receive rituximab IV on day 1, etoposide IV on days 2-4, carboplatin IV on day 3, and ifosfamide IV on day 3 over 24 hours. Patients also receive G-CSF SC once daily beginning on day 6 and continuing until apheresis is completed and plerixafor SC once daily for up to 4 days beginning 24 hours after recovery from nadir and continuing until apheresis is completed. Patients may undergo up to 4 apheresis procedures until the optimal number of CD34+ cells are collected. Carboplatin: Given IV Etoposide: Given IV Filgrastim: Given SC Ifosfamide: Given IV Leukapheresis: Given through catheter Plerixafor: Given SC Rituximab: Given IV
Period Title: Overall Study
STARTED	20
COMPLETED	17
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Treatment (Rituximab, Etoposide, Carboplatin, Ifosfamide)
Arm/Group Description	Patients receive rituximab IV on day 1, etoposide IV on days 2-4, carboplatin IV on day 3, and ifosfamide IV on day 3 over 24 hours. Patients also receive G-CSF SC once daily beginning on day 6 and continuing until apheresis is completed and plerixafor SC once daily for up to 4 days beginning 24 hours after recovery from nadir and continuing until apheresis is completed. Patients may undergo up to 4 apheresis procedures until the optimal number of CD34+ cells are collected. Carboplatin: Given IV Etoposide: Given IV Filgrastim: Given SC Ifosfamide: Given IV Leukapheresis: Given through catheter Plerixafor: Given SC Rituximab: Given IV
Overall Participants	20
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	8 40%
>=65 years	12 60%
Age (Years) [Median (Full Range) ]
Median (Full Range) [Years]	66
Sex: Female, Male (Count of Participants)
Female	6 30%
Male	14 70%
Region of Enrollment (participants) [Number]
United States	20 100%

Outcome Measures

1. Primary Outcome

Title	Number of Patients to Mobilize ≥5 x 10^6 CD34 Cells/kg Autologous PBSC (Efficacy)
Description	Number of patients who achieved ≥5 x 10^6 CD34 cells/kg autologous PBSC collection by apheresis.
Time Frame	One Month

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Rituximab, Etoposide, Carboplatin, Ifosfamide)
Arm/Group Description	Patients receive rituximab IV on day 1, etoposide IV on days 2-4, carboplatin IV on day 3, and ifosfamide IV on day 3 over 24 hours. Patients also receive G-CSF SC once daily beginning on day 6 and continuing until apheresis is completed and plerixafor SC once daily for up to 4 days beginning 24 hours after recovery from nadir and continuing until apheresis is completed. Patients may undergo up to 4 apheresis procedures until the optimal number of CD34+ cells are collected. Carboplatin: Given IV Etoposide: Given IV Filgrastim: Given SC Ifosfamide: Given IV Leukapheresis: Given through catheter Plerixafor: Given SC Rituximab: Given IV
Measure Participants	17
Count of Participants [Participants]	17 85%

2. Primary Outcome

Title	Number of Patients Who Achieved ≥5 x 10^6 CD34 Cells/kg in ≤4 Apheresis Days
Description	Number of patients to collect at least 5 x 10^6 CD34 cells/kg in under 4 apheresis procedures.
Time Frame	Up to Four Apheresis Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Rituximab, Etoposide, Carboplatin, Ifosfamide)
Arm/Group Description	Patients receive rituximab IV on day 1, etoposide IV on days 2-4, carboplatin IV on day 3, and ifosfamide IV on day 3 over 24 hours. Patients also receive G-CSF SC once daily beginning on day 6 and continuing until apheresis is completed and plerixafor SC once daily for up to 4 days beginning 24 hours after recovery from nadir and continuing until apheresis is completed. Patients may undergo up to 4 apheresis procedures until the optimal number of CD34+ cells are collected. Carboplatin: Given IV Etoposide: Given IV Filgrastim: Given SC Ifosfamide: Given IV Leukapheresis: Given through catheter Plerixafor: Given SC Rituximab: Given IV
Measure Participants	17
Count of Participants [Participants]	17 85%

3. Primary Outcome

Title	Number of Participants Requiring One or Two Apheresis Collection Days to Reach ≥5 x 10^6 CD34 Cells/kg
Description	Number of participants requiring one or two apheresis collection days to reach collection goal.
Time Frame	Up to Four Apheresis Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Rituximab, Etoposide, Carboplatin, Ifosfamide)
Arm/Group Description	Patients receive rituximab IV on day 1, etoposide IV on days 2-4, carboplatin IV on day 3, and ifosfamide IV on day 3 over 24 hours. Patients also receive G-CSF SC once daily beginning on day 6 and continuing until apheresis is completed and plerixafor SC once daily for up to 4 days beginning 24 hours after recovery from nadir and continuing until apheresis is completed. Patients may undergo up to 4 apheresis procedures until the optimal number of CD34+ cells are collected. Carboplatin: Given IV Etoposide: Given IV Filgrastim: Given SC Ifosfamide: Given IV Leukapheresis: Given through catheter Plerixafor: Given SC Rituximab: Given IV
Measure Participants	17
One apheresis collection day	15 75%
Two apheresis collection days	2 10%
Three apheresis collection days	0 0%
Four apheresis collection days	0 0%

4. Primary Outcome

Title	Total Number of Participants Who Did Not Collect ≥5 x 10^6 CD34 Cells/kg in a Maximum of Four Apheresis Days
Description	Number of participants who did not collect ≥5 x 10^6 CD34 cells/kg in up to four apheresis days
Time Frame	Up to Four Apheresis Days

Outcome Measure Data

Analysis Population Description

Note: No patients were in this category.

Arm/Group Title	Treatment (Rituximab, Etoposide, Carboplatin, Ifosfamide)
Arm/Group Description	Patients receive rituximab IV on day 1, etoposide IV on days 2-4, carboplatin IV on day 3, and ifosfamide IV on day 3 over 24 hours. Patients also receive G-CSF SC once daily beginning on day 6 and continuing until apheresis is completed and plerixafor SC once daily for up to 4 days beginning 24 hours after recovery from nadir and continuing until apheresis is completed. Patients may undergo up to 4 apheresis procedures until the optimal number of CD34+ cells are collected. Carboplatin: Given IV Etoposide: Given IV Filgrastim: Given SC Ifosfamide: Given IV Leukapheresis: Given through catheter Plerixafor: Given SC Rituximab: Given IV
Measure Participants	17
Count of Participants [Participants]	0 0%

Adverse Events

Arm/Group Title	Treatment (Rituximab, Etoposide, Carboplatin, Ifosfamide)
Arm/Group Description	Patients receive rituximab IV on day 1, etoposide IV on days 2-4, carboplatin IV on day 3, and ifosfamide IV on day 3 over 24 hours. Patients also receive G-CSF SC once daily beginning on day 6 and continuing until apheresis is completed and plerixafor SC once daily for up to 4 days beginning 24 hours after recovery from nadir and continuing until apheresis is completed. Patients may undergo up to 4 apheresis procedures until the optimal number of CD34+ cells are collected. Carboplatin: Given IV Etoposide: Given IV Filgrastim: Given SC Ifosfamide: Given IV Leukapheresis: Given through catheter Plerixafor: Given SC Rituximab: Given IV
All Cause Mortality
	Treatment (Rituximab, Etoposide, Carboplatin, Ifosfamide)
	Affected / at Risk (%)	# Events
Total	5/20 (25%)
Serious Adverse Events
	Treatment (Rituximab, Etoposide, Carboplatin, Ifosfamide)
	Affected / at Risk (%)	# Events
Total	2/20 (10%)
Blood and lymphatic system disorders
Febrile Neutropenia	1/20 (5%)
Cardiac disorders
Atrial Fibrillation	1/20 (5%)
Other (Not Including Serious) Adverse Events
	Treatment (Rituximab, Etoposide, Carboplatin, Ifosfamide)
	Affected / at Risk (%)	# Events
Total	3/20 (15%)
Infections and infestations
Cellulitis	1/20 (5%)
Metabolism and nutrition disorders
Hyperglycemia	2/20 (10%)
Vascular disorders
DVT	1/20 (5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.