Optimized Donor Selection, Nonmyeloablative BMT for B-cell Lymphomas With Post-transplantation Cy and Rituximab

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00946023
• Collaborator: (none)
• Enrollment: 135
• Location: 1
• Arm: 1
• Actual Duration (Months): 48.5
• Patients Per Site Per Month: 2.8

Study Details

Study Description

Brief Summary

This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation and rituximab works in treating patients with B-cell lymphoma or chronic lymphocytic leukemia who are undergoing an allogeneic (donor) bone marrow transplant. The type of bone marrow transplant is a less intensive or "mini" transplant using a relative as the bone marrow donor. The donated bone marrow stem cells may replace the patient's immune system cells and help destroy any remaining cancer (graft-versus-tumor effect). Patients undergoing this type of transplant often have more than one relative who could be a donor. The trial is also studying a new way of choosing amongst possible donors which might improve how the rituximab works.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma; B-cell Lymphoma; Non Hodgkin Lymphoma; Chronic Lymphocytic Leukemia	Drug: Fludarabine; Drug: Cyclophosphamide; Radiation: Total body irradiation; Drug: Tacrolimus; Drug: Mycophenolate Mofetil; Drug: Rituximab; Biological: Allogeneic Bone Marrow Transplant (BMT)	Phase 2

Detailed Description

This phase II for relapsed or refractory B-cell malignancies builds on the platform of nonmyeloablative, related-donor, HLA (human leukocyte antigen)-matched or HLA-haploidentical BMT with post-transplantation high-dose cyclosphosphamide administered for prophylaxis of graft-versus-host disease and graft rejection. Rituximab is added to the transplant regimen with the goal of augmenting anti-tumor activity. In patients with B-cell lymphomas, specific polymorphisms in the immunoglobulin Fc receptor have been associated with greater sensitivity to rituximab or rituximab-based therapies, translating in some series into higher response rates and improved progression-free survival. This raises the possibility of selecting donors who carry this permissive polymorphism. This trial identifies and selects donors who have the favorable polymorphism at FcgammaR3A-158, thereby potentially conferring greater sensitivity to rituximab in the host after BMT.

Study Design

• Study Type: Interventional
• Actual Enrollment: 135 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Nonmyeloablative BMT With Post-transplant Cyclophosphamide, Rituximab and Optimized Donor Selection for B-cell Lymphomas
• Actual Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Jul 1, 2013
• Actual Study Completion Date: Jul 17, 2013

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Transplant Non-myeloablative allogeneic bone marrow transplant (BMT) with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD (graft vs host disease) prophylaxis. Rituximab will be given as post-transplant maintenance.

Drug: Fludarabine; Days -6 through -2: 30 mg/m^2 IV daily; Other Names: Fludara ; Drug: Cyclophosphamide; Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily; Other Names: Cytoxan CTX Cy ; Radiation: Total body irradiation; Day -1: 200 centigray (cGy) in a single fraction; Other Names: TBI ; Drug: Tacrolimus; Start on Day 5 through Day 180; Other Names: FK-506 FK506 Prograf ; Drug: Mycophenolate Mofetil; Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day); Other Names: MMF CellCept ; Drug: Rituximab; Day 30 and every week after for 8 total doses: 375 mg/m^2 IV; Other Names: Rituxan ; Biological: Allogeneic Bone Marrow Transplant (BMT); Day 0: Donor bone marrow infusion

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival [1 year post-intervention]

   Percentage of participants alive and without relapse or disease progression.

Secondary Outcome Measures

1. Progression-free Survival [2 years post-intervention]

   Percentage of participants alive with and without relapse.

2. Overall Survival [1 year post intervention]

   Percentage of participants alive.

3. Overall Survival [2 years post intervention]

   Percentage of participants alive.

4. Relapse [1 year post intervention]

   Percentage of participants alive with relapse or disease progression.

5. Relapse [2 years post intervention]

   Percentage of participants alive with relapse or disease progression.

6. Non-relapse Mortality [1 year post intervention]

   Percentage of participants who died due to BMT-related reasons.

7. Incidence of Grades II-IV Acute Graft-versus-Host-Disease (GVHD) [1 year post intervention]

   Percentage of participants who experienced grade II, III, or IV acute GVHD. Acute GVHD is graded using the Przepiorka criteria.

8. Incidence of Grades III-IV Acute GVHD [1 year post intervention]

   Percentage of participants who experienced grade II, III, or IV acute GVHD. Acute GVHD is graded using the Przepiorka criteria.

9. Incidence of Chronic GVHD [1 year post intervention]

   Percentage of participants who experienced chronic GVHD. Chronic GVHD is graded using NIH consensus criteria and Seattle criteria.

10. Engraftment [Day 60]

    Percentage of patients who engrafted neutrophils and platelets.

11. Graft Failure [Day 60]

    Percentage of participants who failed to engraft.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Year to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Poor-risk CD20+, B-cell lymphoma, as follows:

• Low grade B-cell lymphoma that has failed at least two prior therapies (excluding single agent rituximab), or undergone histologic conversion (if histologic conversion, PR or CR is required):

1. Follicular grade 1 or 2 lymphoma

2. Follicular lymphoma not otherwise specified

3. Marginal zone (or MALT) lymphoma

4. Lymphoplasmacytic lymphoma / Waldenstrom's macroglobulinemia

5. Hairy cell leukemia

6. Small lymphocytic lymphoma / chronic lymphocytic leukemia (SLL/CLL)

7. Low grade B-cell lymphoma, unspecified

8. Nodular lymphocyte-predominant Hodgkin lymphoma

• Poor-risk small lymphocytic lymphoma or chronic lymphocytic leukemia, defined by a 17p deletion, 11q deletion, or histologic conversion (if histologic conversion, PR or CR is required)

• Aggressive B-cell non-Hodgkin's lymphoma that has failed at least one prior regimen of multiagent chemotherapy, is in PR (partial remission) or CR (complete remission), and patient is either ineligible for autologous hematopoietic BMT or autologous BMT is not recommended:

1. Follicular grade 3 lymphoma

2. Histoconversion of low-grade B-cell lymphoma (including SLL/CLL) to aggressive B-cell non-Hodgkin's lymphoma

3. Mantle cell lymphoma

4. Diffuse large B-cell lymphoma (excluding primary CNS [central nervous system] lymphoma)

5. "Gray zone" or composite lymphomas with combined features of primary mediastinal large B-cell and Hodgkin's lymphoma

6. Burkitt's lymphoma/leukemia

7. Atypical Burkitt's lymphoma/leukemia (high grade B-cell lymphoma, unclassified, including that with features intermediate between Burkitt's and diffuse large B-cell lymphoma)

• Must have a related donor who is at least HLA haploidentical

• Any previous BMT must have occurred at least 3 months prior

• Left ventricular ejection fraction at least 35%

• Bilirubin no more than 3.0 mg/dL (unless due to Gilbert's syndrome), and ALT (alanine aminotransferase) and AST (aspartate aminotransferase) no more than 5 x upper limit of normal

• FEV1 (forced expiratory volume in one second) and FVC (forced vital capacity) at least 40% of predicted

• Absence of uncontrolled infection

Exclusion Criteria:

• More than 20% involvement of bone marrow by chronic lymphocytic leukemia

• Active central nervous system lymphoma

• ECOG (Eastern Cooperative Oncology Group) performance status greater than 1 (2,3, and

• HIV positive

• Pregnant or breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231

Sponsors and Collaborators

• Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Investigators

• Principal Investigator: Yvette L Kasamon, MD, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• ClinicalTrials.gov Identifier: NCT00946023
• Other Study ID Numbers: J0941; NA_00025589
• First Posted: Jul 24, 2009
• Last Update Posted: Aug 27, 2018
• Last Verified: Jul 1, 2018

• Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins: lymphoma; non hodgkin lymphoma; allogeneic; bone marrow transplantation; nonmyeloablative; cyclophosphamide; rituximab
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Mycophenolic Acid; Cyclophosphamide; Rituximab; Fludarabine; Tacrolimus

Study Results

Participant Flow

Pre-assignment Detail	52 participants were screen failures and did not proceed on the study.

Arm/Group Title	Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Rituximab will be given as post-transplant maintenance. Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 180 Mycophenolate Mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day) Rituximab: Day 30 and every week after for 8 total doses: 375 mg/m^2 IV
Period Title: Overall Study
STARTED	83
COMPLETED	83
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Rituximab will be given as post-transplant maintenance. Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 180 Mycophenolate Mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day) Rituximab: Day 30 and every week after for 8 total doses: 375 mg/m^2 IV
Overall Participants	83
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	59
Age, Customized (Count of Participants)
>= 60 years old	39 47%
Sex: Female, Male (Count of Participants)
Female	27 32.5%
Male	56 67.5%
Region of Enrollment (participants) [Number]
United States	83 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival
Description	Percentage of participants alive and without relapse or disease progression.
Time Frame	1 year post-intervention

Outcome Measure Data

Analysis Population Description

Populations were analyzed as follows: All participants Recipients of haploidentical donors (69 participants) Recipients of VV, VF, and FF donors (17, 43, and 23 participants, respectively, totaling 83 participants)

Arm/Group Title	Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Rituximab will be given as post-transplant maintenance. Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 180 Mycophenolate Mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day) Rituximab: Day 30 and every week after for 8 total doses: 375 mg/m^2 IV
Measure Participants	83
All participants	71 85.5%
Haploidentical recipients	70 84.3%
VV donor	82 98.8%
VF donor	70 84.3%
FF donor	65 78.3%

2. Secondary Outcome

Title	Progression-free Survival
Description	Percentage of participants alive with and without relapse.
Time Frame	2 years post-intervention

Outcome Measure Data

Analysis Population Description

Populations were analyzed as follows: All participants Recipients of haploidentical donors (69 participants) Recipients of VV, VF, and FF donors (17, 43, and 23 participants, respectively, totaling 83 participants)

Arm/Group Title	Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Rituximab will be given as post-transplant maintenance. Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 180 Mycophenolate Mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day) Rituximab: Day 30 and every week after for 8 total doses: 375 mg/m^2 IV
Measure Participants	83
All participants	60 72.3%
Haploidentical recipients	63 75.9%
VV donor	68 81.9%
VF donor	59 71.1%
FF donor	56 67.5%

3. Secondary Outcome

Title	Overall Survival
Description	Percentage of participants alive.
Time Frame	1 year post intervention

Outcome Measure Data

Analysis Population Description

Populations were analyzed as follows: All participants Recipients of haploidentical donors (69 participants) Recipients of VV, VF, and FF donors (17, 43, and 23 participants, respectively, totaling 83 participants)

Arm/Group Title	Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Rituximab will be given as post-transplant maintenance. Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 180 Mycophenolate Mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day) Rituximab: Day 30 and every week after for 8 total doses: 375 mg/m^2 IV
Measure Participants	83
All participants	86 103.6%
Haploidentical recipients	83 100%
VV donor	94 113.3%
VF donor	86 103.6%
FF donor	78 94%

4. Secondary Outcome

Title	Overall Survival
Description	Percentage of participants alive.
Time Frame	2 years post intervention

Outcome Measure Data

Analysis Population Description

Populations were analyzed as follows: All participants Recipients of haploidentical donors (69 participants) Recipients of VV, VF, and FF donors (17, 43, and 23 participants, respectively, totaling 83 participants)

Arm/Group Title	Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Rituximab will be given as post-transplant maintenance. Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 180 Mycophenolate Mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day) Rituximab: Day 30 and every week after for 8 total doses: 375 mg/m^2 IV
Measure Participants	83
All participants	76 91.6%
Haploidentical recipients	73 88%
VV donor	87 104.8%
VF donor	76 91.6%
FF donor	69 83.1%

5. Secondary Outcome

Title	Relapse
Description	Percentage of participants alive with relapse or disease progression.
Time Frame	1 year post intervention

Outcome Measure Data

Analysis Population Description

Populations were analyzed as follows: All participants Recipients of haploidentical donors (69 participants) Recipients of VV, VF, and FF donors (17, 43, and 23 participants, respectively, totaling 83 participants)

Arm/Group Title	Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Rituximab will be given as post-transplant maintenance. Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 180 Mycophenolate Mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day) Rituximab: Day 30 and every week after for 8 total doses: 375 mg/m^2 IV
Measure Participants	83
All participants	20 24.1%
Haploidentical recipients	20 24.1%
VV donor	18 21.7%
VF donor	23 27.7%
FF donor	17 20.5%

6. Secondary Outcome

Title	Relapse
Description	Percentage of participants alive with relapse or disease progression.
Time Frame	2 years post intervention

Outcome Measure Data

Analysis Population Description

Populations were analyzed as follows: All participants Recipients of haploidentical donors (69 participants) Recipients of VV, VF, and FF donors (17, 43, and 23 participants, respectively, totaling 83 participants)

Arm/Group Title	Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Rituximab will be given as post-transplant maintenance. Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 180 Mycophenolate Mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day) Rituximab: Day 30 and every week after for 8 total doses: 375 mg/m^2 IV
Measure Participants	83
All participants	27 32.5%
Haploidentical recipients	23 27.7%
VV donor	25 30.1%
VF donor	31 37.3%
FF donor	22 26.5%

7. Secondary Outcome

Title	Non-relapse Mortality
Description	Percentage of participants who died due to BMT-related reasons.
Time Frame	1 year post intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Rituximab will be given as post-transplant maintenance. Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 180 Mycophenolate Mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day) Rituximab: Day 30 and every week after for 8 total doses: 375 mg/m^2 IV
Measure Participants	83
Number (95% Confidence Interval) [percentage of participants]	8 9.6%

8. Secondary Outcome

Title	Incidence of Grades II-IV Acute Graft-versus-Host-Disease (GVHD)
Description	Percentage of participants who experienced grade II, III, or IV acute GVHD. Acute GVHD is graded using the Przepiorka criteria.
Time Frame	1 year post intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Rituximab will be given as post-transplant maintenance. Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 180 Mycophenolate Mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day) Rituximab: Day 30 and every week after for 8 total doses: 375 mg/m^2 IV
Measure Participants	83
Number (95% Confidence Interval) [percentage of participants]	41 49.4%

9. Secondary Outcome

Title	Incidence of Grades III-IV Acute GVHD
Description	Percentage of participants who experienced grade II, III, or IV acute GVHD. Acute GVHD is graded using the Przepiorka criteria.
Time Frame	1 year post intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Rituximab will be given as post-transplant maintenance. Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 180 Mycophenolate Mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day) Rituximab: Day 30 and every week after for 8 total doses: 375 mg/m^2 IV
Measure Participants	83
Number (95% Confidence Interval) [percentage of participants]	5 6%

10. Secondary Outcome

Title	Incidence of Chronic GVHD
Description	Percentage of participants who experienced chronic GVHD. Chronic GVHD is graded using NIH consensus criteria and Seattle criteria.
Time Frame	1 year post intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Rituximab will be given as post-transplant maintenance. Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 180 Mycophenolate Mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day) Rituximab: Day 30 and every week after for 8 total doses: 375 mg/m^2 IV
Measure Participants	83
Number (95% Confidence Interval) [percentage of participants]	11 13.3%

11. Secondary Outcome

Title	Engraftment
Description	Percentage of patients who engrafted neutrophils and platelets.
Time Frame	Day 60

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Rituximab will be given as post-transplant maintenance. Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 180 Mycophenolate Mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day) Rituximab: Day 30 and every week after for 8 total doses: 375 mg/m^2 IV
Measure Participants	83
Neutrophil engraftment	98 118.1%
Platelet engraftment	98 118.1%

12. Secondary Outcome

Title	Graft Failure
Description	Percentage of participants who failed to engraft.
Time Frame	Day 60

Outcome Measure Data

Analysis Population Description

Two participants were not analyzed because they died prior to Day 60.

Arm/Group Title	Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Rituximab will be given as post-transplant maintenance. Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 180 Mycophenolate Mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day) Rituximab: Day 30 and every week after for 8 total doses: 375 mg/m^2 IV
Measure Participants	81
Count of Participants [Participants]	2 2.4%

Adverse Events

Time Frame	1 year
Adverse Event Reporting Description	Adverse events were assessed by the investigator and by labwork at each study visit as per protocol.
Arm/Group Title	Transplant
Arm/Group Description	Non-myeloablative bone marrow transplant with a fludarabine (Flu), cyclophosphamide (Cy), total body irradiation (TBI) preparative regimen and post-transplant Cy, mycophenolate mofetil (MMF), and tacrolimus as GVHD prophylaxis. Rituximab will be given as post-transplant maintenance. Fludarabine: Days -6 through -2: 30 mg/m^2 IV daily Cyclophosphamide: Days -6 and -5: 14.5 mg/kg IV daily; Days 3 and 4: 50 mg/kg IV daily Total body irradiation: Day -1: 200 centigray (cGy) in a single fraction Tacrolimus: Start on Day 5 through Day 180 Mycophenolate Mofetil: Days 5 through 35: 15 mg/kg PO three times daily (max 3 g/day) Rituximab: Day 30 and every week after for 8 total doses: 375 mg/m^2 IV
All Cause Mortality
	Transplant
	Affected / at Risk (%)	# Events
Total	34/83 (41%)
Serious Adverse Events
	Transplant
	Affected / at Risk (%)	# Events
Total	56/83 (67.5%)
Blood and lymphatic system disorders
Neutropenia	4/83 (4.8%)	4
Pancytopenia	1/83 (1.2%)	1
Thrombocytopenia	3/83 (3.6%)	3
Bleeding	3/83 (3.6%)	3
Deep vein thrombosis	4/83 (4.8%)	4
Cardiac disorders
Atrial fibrillation	2/83 (2.4%)	2
Left ventricular systolic dysfunction	1/83 (1.2%)	2
Hypotension	5/83 (6%)	5
Tachycardia	1/83 (1.2%)	1
Volume overload	3/83 (3.6%)	3
Gastrointestinal disorders
Dehydration	2/83 (2.4%)	2
Abdominal pain	4/83 (4.8%)	4
Cholelithiasis	1/83 (1.2%)	1
Diarrhea	8/83 (9.6%)	9
Vomiting	2/83 (2.4%)	2
Odynophagia	1/83 (1.2%)	1
Pancreatitis	2/83 (2.4%)	2
Colitis	1/83 (1.2%)	1
General disorders
Chest pain	2/83 (2.4%)	2
Rigors/chills	5/83 (6%)	5
Failure to thrive	1/83 (1.2%)	1
Fever	1/83 (1.2%)	1
Multiple organ dysfunction syndrome	1/83 (1.2%)	1
Hepatobiliary disorders
Liver failure	1/83 (1.2%)	1
Immune system disorders
Allergic reaction	3/83 (3.6%)	3
Hemophagocytic syndrome	1/83 (1.2%)	1
Infections and infestations
Infection	48/83 (57.8%)	132
Investigations
Hyperkalemia	1/83 (1.2%)	1
Hypogammaglobulinemia	1/83 (1.2%)	1
Metabolism and nutrition disorders
Metabolic acidosis	1/83 (1.2%)	1
Respiratory acidosis	1/83 (1.2%)	1
Musculoskeletal and connective tissue disorders
Hip fracture	1/83 (1.2%)	1
Knee pain	1/83 (1.2%)	1
Nervous system disorders
Altered consciousness	7/83 (8.4%)	9
Optic neuritis	1/83 (1.2%)	1
Renal and urinary disorders
Renal failure	8/83 (9.6%)	8
Respiratory, thoracic and mediastinal disorders
Pneumonitis	1/83 (1.2%)	1
Cough	3/83 (3.6%)	4
Respiratory failure	6/83 (7.2%)	7
Pulmonary embolism	3/83 (3.6%)	3
Dyspnea	2/83 (2.4%)	4
Pleural effusion	1/83 (1.2%)	1
Bronchitis	1/83 (1.2%)	1
Sinusitis	1/83 (1.2%)	1
Skin and subcutaneous tissue disorders
Rash	3/83 (3.6%)	4
Other (Not Including Serious) Adverse Events
	Transplant
	Affected / at Risk (%)	# Events
Total	62/83 (74.7%)
Blood and lymphatic system disorders
Neutropenia	5/83 (6%)	7
General disorders
Fever	5/83 (6%)	5
Infections and infestations
Infection	46/83 (55.4%)	86
Neutropenic fever	11/83 (13.3%)	13
Respiratory, thoracic and mediastinal disorders
Sinusitis	5/83 (6%)	5
Skin and subcutaneous tissue disorders
Rash	33/83 (39.8%)	43

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.