Rituximab in Treating Patients Undergoing Donor Peripheral Blood Stem Cell Transplant for Relapsed or Refractory B-cell Lymphoma

• ClinicalTrials.gov Identifier: NCT00867529
• Recruitment Status: Completed
• First Posted: March 23, 2009
• Results First Posted: May 22, 2017
• Last Update Posted: January 2, 2018
• Sponsor: Fred Hutchinson Cancer Research Center
• Collaborators: American Cancer Society, Inc.; National Cancer Institute (NCI)
• Information provided by (Responsible Party): David Maloney, Fred Hutchinson Cancer Research Center

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; B-cell Chronic Lymphocytic Leukemia; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Acute Lymphoblastic Leukemia; 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 Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell 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 Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia
• Interventions: Biological: rituximab; Procedure: peripheral blood stem cell transplantation; Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation; Other: pharmacological study; Other: laboratory biomarker analysis
• Enrollment: 63

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Treatment (Rituximab Pre- and Post-transplant)
Arm/Group Description	Patients receive rituximab IV, pre- and post-transplant, on days -3, 10, 24, and 38. Patients undergo donor peripheral blood stem cell transplant on day 0. Treatment continues in the absence of disease progression or unacceptable toxicity. rituximab: Given IV peripheral blood stem cell transplantation: Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation nonmyeloablative allogeneic hematopoietic stem cell transplantation: Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies
Period Title: Overall Study
Started	63
Completed	63
Not Completed	0

Baseline Characteristics

Arm/Group Title		Treatment (Rituximab Pre- and Post-transplant)
Arm/Group Description		Patients receive rituximab IV, pre- and post-transplant, on days -3, 10, 24, and 38. Patients undergo donor peripheral blood stem cell transplant on day 0. Treatment continues in the absence of disease progression or unacceptable toxicity. rituximab: Given IV peripheral blood stem cell transplantation: Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation nonmyeloablative allogeneic hematopoietic stem cell transplantation: Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies
Overall Number of Baseline Participants		63
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	63 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	57 90.5%
	>=65 years	6 9.5%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	63 participants
	Female	20 31.7%
	Male	43 68.3%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	63 participants
	Hispanic or Latino	5 7.9%
	Not Hispanic or Latino	58 92.1%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	63 participants
	American Indian or Alaska Native	1 1.6%
	Asian	2 3.2%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	58 92.1%
	More than one race	0 0.0%
	Unknown or Not Reported	2 3.2%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	63 participants
		63

Outcome Measures

1. Primary Outcome

Title	Disease Relapse Rate
Description	Number of patients with relapsed/progressive disease post-transplant. The effectiveness of pre- and post-transplant rituximab in decreasing the rate of relapse will be evaluated.
Time Frame	At 18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Rituximab Pre- and Post-transplant)
Arm/Group Description:	Patients receive rituximab IV, pre- and post-transplant, on days -3, 10, 24, and 38. Patients undergo donor peripheral blood stem cell transplant on day 0. Treatment continues in the absence of disease progression or unacceptable toxicity. rituximab: Given IV peripheral blood stem cell transplantation: Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation nonmyeloablative allogeneic hematopoietic stem cell transplantation: Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies
Overall Number of Participants Analyzed	63
Measure Type: Count of Participants; Unit of Measure: Participants
	18 28.6%

2. Secondary Outcome

Title	Incidence and Severity of Acute and Chronic GVHD Evaluated Per an Adapted Version of Common Terminology Criteria for Adverse Events (CTCAE) Version 2.0
Description	Number of patients who developed acute/chronic GVHD post-transplant. A chronic GVHD diagnosis ≥1 manifestation that is distinctive for chronic GVHD, as opposed to acute GVHD. aGVHD Stages Skin: a maculopapular eruption involving < 25% BSA a maculopapular eruption involving 25 - 50% BSA generalized erythroderma generalized erythroderma with bullous formation and often with desquamation Liver: bilirubin 2.0 - 3.0 mg/100 mL bilirubin 3 - 5.9 mg/100 mL bilirubin 6 - 14.9 mg/100 mL bilirubin > 15 mg/100 mL Gut: Diarrhea is graded 1 - 4 in severity. Nausea and vomiting and/or anorexia caused by GVHD is assigned as 1 in severity. The severity of gut involvement is assigned to the most severe involvement noted. Patients with visible bloody diarrhea are at least stage 2 gut and grade 3 overall. aGVHD Grades Grade III: Stage 2 - 4 gut involvement and/or stage 2 - 4 liver involvement Grade IV: Pattern and severity of GVHD similar to grade 3 with extreme constitutional symptoms or death
Time Frame	Through day +100 after transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Rituximab Pre- and Post-transplant)
Arm/Group Description:	Patients receive rituximab IV, pre- and post-transplant, on days -3, 10, 24, and 38. Patients undergo donor peripheral blood stem cell transplant on day 0. Treatment continues in the absence of disease progression or unacceptable toxicity. rituximab: Given IV peripheral blood stem cell transplantation: Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation nonmyeloablative allogeneic hematopoietic stem cell transplantation: Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies
Overall Number of Participants Analyzed	63
Measure Type: Count of Participants; Unit of Measure: Participants
	17 27.0%

3. Secondary Outcome

Title	Overall Survival and Progression-free Survival
Description	Number of patients surviving and number of patients surviving without progressive/relapsed disease, post-transplant.
Time Frame	At 6 months and then every year thereafter, up to 18 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Rituximab Pre- and Post-transplant)
Arm/Group Description:	Patients receive rituximab IV, pre- and post-transplant, on days -3, 10, 24, and 38. Patients undergo donor peripheral blood stem cell transplant on day 0. Treatment continues in the absence of disease progression or unacceptable toxicity. rituximab: Given IV peripheral blood stem cell transplantation: Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation nonmyeloablative allogeneic hematopoietic stem cell transplantation: Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies
Overall Number of Participants Analyzed	63
Measure Type: Count of Participants; Unit of Measure: Participants
PFS - 6 Months	48 76.2%
PFS - 1 Year	39 61.9%
PFS - 1.5 Years	34 54.0%
OS - 6 Months	52 82.5%
OS - 1 Year	44 69.8%
OS - 1.5 Years	36 57.1%

4. Secondary Outcome

Title	Rate of Graft Rejection and Graft Failure
Description	Number of patients experiencing graft rejection and/or graft failure
Time Frame	18 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Rituximab Pre- and Post-transplant)
Arm/Group Description:	Patients receive rituximab IV, pre- and post-transplant, on days -3, 10, 24, and 38. Patients undergo donor peripheral blood stem cell transplant on day 0. Treatment continues in the absence of disease progression or unacceptable toxicity. rituximab: Given IV peripheral blood stem cell transplantation: Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation nonmyeloablative allogeneic hematopoietic stem cell transplantation: Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies
Overall Number of Participants Analyzed	63
Measure Type: Count of Participants; Unit of Measure: Participants
Graft Rejection	1 1.6%
Graft Failure	0 0.0%

5. Secondary Outcome

Title	Time to Engraftment
Description	Median time from transplant to engraftment.
Time Frame	18 Months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Rituximab Pre- and Post-transplant)
Arm/Group Description:	Patients receive rituximab IV, pre- and post-transplant, on days -3, 10, 24, and 38. Patients undergo donor peripheral blood stem cell transplant on day 0. Treatment continues in the absence of disease progression or unacceptable toxicity. rituximab: Given IV peripheral blood stem cell transplantation: Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation nonmyeloablative allogeneic hematopoietic stem cell transplantation: Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies
Overall Number of Participants Analyzed	63
Median (Full Range); Unit of Measure: Days
	10; (0 to 48)

Adverse Events

Time Frame	AEs: Conditioning through Day 100; SAEs: Conditioning through Day 200
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Treatment (Rituximab Pre- and Post-transplant)
Arm/Group Description	Patients receive rituximab IV, pre- and post-transplant, on days -3, 10, 24, and 38. Patients undergo donor peripheral blood stem cell transplant on day 0. Treatment continues in the absence of disease progression or unacceptable toxicity. rituximab: Given IV peripheral blood stem cell transplantation: Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation nonmyeloablative allogeneic hematopoietic stem cell transplantation: Undergo nonmyeloablative allogeneic peripheral blood/hematopoietic stem cell transplantation pharmacological study: Correlative studies laboratory biomarker analysis: Correlative studies
All-Cause Mortality
	Treatment (Rituximab Pre- and Post-transplant)
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Treatment (Rituximab Pre- and Post-transplant)
	Affected / at Risk (%)	# Events
Total	5/63 (7.94%)
Infections and infestations
Death Due to Infection *	2/63 (3.17%)	2
Sepsis and Tachycardia *	1/63 (1.59%)	1
Sepsis, Respiratory Failure, Mental Status Change *	1/63 (1.59%)	1
Respiratory, thoracic and mediastinal disorders
Multiple Pulmonary Emboli *	1/63 (1.59%)	1
Suspected Pulmonary Embolism *	1/63 (1.59%)	1
* Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Treatment (Rituximab Pre- and Post-transplant)
	Affected / at Risk (%)	# Events
Total	15/63 (23.81%)
Hepatobiliary disorders
Elevated Bilirubin †	4/63 (6.35%)	4
Renal and urinary disorders
Elevated Creatinine †	5/63 (7.94%)	5
Respiratory, thoracic and mediastinal disorders
ARDS *	3/63 (4.76%)	3
Diffuse Alveolar Hemorrhage *	3/63 (4.76%)	3
Hypoxia *	11/63 (17.46%)	12
† Indicates events were collected by systematic assessment; * Indicates events were collected by non-systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: David G Maloney, MD PhD
• Organization: Fred Hutch
• EMail: dmaloney@fredhutch.org

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Shadman M, Maloney DG, Storer B, Sandmaier BM, Chauncey TR, Smedegaard Andersen N, Niederwieser D, Shizuru J, Bruno B, Pulsipher MA, Maziarz RT, Agura ED, Hari P, Langston AA, Maris MB, McSweeney PA, Storb R, Sorror ML. Rituximab-based allogeneic transplant for chronic lymphocytic leukemia with comparison to historical experience. Bone Marrow Transplant. 2020 Jan;55(1):172-181. doi: 10.1038/s41409-019-0660-8. Epub 2019 Sep 3.

• Responsible Party: David Maloney, Fred Hutchinson Cancer Research Center
• ClinicalTrials.gov Identifier: NCT00867529
• Other Study ID Numbers: 2226.00; NCI-2010-00107 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 2226; 2226.00 ( Other Identifier: Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium ); P01CA078902 ( U.S. NIH Grant/Contract ); P30CA015704 ( U.S. NIH Grant/Contract )
• First Submitted: March 20, 2009
• First Posted: March 23, 2009
• Results First Submitted: April 14, 2017
• Results First Posted: May 22, 2017
• Last Update Posted: January 2, 2018