Autologous Transplant in HIV Patients (BMT CTN 0803)

• Sponsor: Medical College of Wisconsin (Other)
• Overall Status: Completed
• CT.gov ID: NCT01141712
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH), National Cancer Institute (NCI) (NIH), Blood and Marrow Transplant Clinical Trials Network (Other), National Marrow Donor Program (Other)
• Enrollment: 43
• Locations: 16
• Arm: 1
• Duration (Months): 74
• Patients Per Site: 2.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

This study is a Phase II, multicenter trial assessing overall survival after autologous hematopoietic stem cell transplantation using a BEAM transplant regimen (carmustine, etoposide, cytarabine, melphalan) in lymphoma patients with HIV.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma; HIV	Procedure: Autologous transplant; Drug: BCNU; Drug: Etoposide; Drug: Cytarabine; Drug: Melphalan	Phase 2

Detailed Description

BACKGROUND:

Non-Hodgkin lymphoma (NHL) is an AIDS-defining diagnosis for patients infected with the Human Immunodeficiency Virus (HIV). While the incidence of NHL has decreased amongst HIV-infected patients since the advent of highly-active anti-retroviral therapy (HAART), lymphoma remains a significant cause of death for this patient population. The prognosis for patients with AIDS-related lymphoma is dramatically different in the era of HAART therapy. In a comparison of treatment outcomes for patients treated before and after the advent of HAART, there is a statistically significant improvement in the overall survival of patients treated with HAART. Unfortunately, despite considerable advances in the treatment of AIDS-related NHL, induction-failure and disease relapse remain key challenges. The prognosis for patients with refractory and relapsed NHL is poor with overall survival rates of less than 20 percent for patients treated with non-transplant salvage therapies. Based upon a randomized trial and numerous phase II trials, high-dose therapy with autologous hematopoietic cell transplantation (HCT) has been established as the standard of care for patients with chemotherapy-sensitive relapsed non-Hodgkin lymphoma.

DESIGN NARRATIVE:

All patients must have chemosensitive disease as demonstrated by response to induction or salvage chemotherapy. Patients must also have less than or equal to 10percent bone marrow involvement after their most recent salvage therapy. Patients cannot have had prior autologous or allogeneic HCT. Patients must initiate conditioning therapy within 3 months of mobilization or bone marrow harvest.

Mobilization therapy may be employed per institutional guidelines. Patients must have an adequate autograft to be eligible for the protocol. Patients may not have HIV refractory to pharmacologic therapy. Patients must not have opportunistic infection that is not responding to therapy. Patients will receive Carmustine (BCNU) 300 mg/m^{2 Day -6, Etoposide 100 mg/m}2 twice a day (BID) on Days -5 to -2, Cytarabine 100 mg/m2 BID on Days -5 to -2, and Melphalan 140 mg/m2 Day -1 followed by autologous HCT.

Patients will be followed for 2 years post-transplant. Survival data, time to progression data, progression-free survival data, time to progression after Complete Remission (CR) data, lymphoma disease-free survival data, time to hematopoietic recovery data, hematologic function data, toxicity data, incidence of infections, treatment-related mortality data, immunologic reconstitution data, data assessing the impact of therapy on the HIV reservoir and microbial gut translocation will be recorded and reported periodically to the BMT CTN Data and Coordinating Center (DCC).

Study Design

• Study Type: Interventional
• Actual Enrollment: 43 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: High Dose Chemotherapy With Autologous Stem Cell Rescue for Aggressive B Cell Lymphoma and Hodgkin Lymphoma in HIV-infected Patients (BMT CTN #0803)
• Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: Jun 1, 2016

Arms and Interventions

Arm

Intervention/Treatment

Other: Autologous transplant Patients will receive BCNU 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 BID Days -5 to -2, Cytarabine 100 mg/m^2 BID Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by autologous HCT.

Procedure: Autologous transplant; Participants will receive the BEAM conditioning regimen followed by autologous HCT.; Drug: BCNU; Participants will receive BCNU 300 mg/m^2 Day -6; Other Names: Carmustine ; Drug: Etoposide; Participants will receive Etoposide 100 mg/m^2 BID Days -5 to -2; Other Names: VP-16 ; Drug: Cytarabine; Participants will receive Cytarabine 100 mg/m^2 BID Days -5 to -2; Other Names: Depocyt ; Drug: Melphalan; Participants will receive Melphalan 140 mg/m^2 Day -1; Other Names: Alkeran

Outcome Measures

Primary Outcome Measures

1. Overall Survival (OS) [Year 1 and 2]

   Assess the OS after autologous hematopoietic stem cell transplantation (HCT) for chemotherapy-sensitive aggressive B cell lymphoma or Hodgkin's lymphoma in patients with HIV using BEAM for pre-transplant conditioning. The primary analysis will consist of estimating the 1 year OS probability from the time of transplantation based on the Kaplan-Meier product limit estimator. The 1 year and 2 year OS and confidence interval will be calculated.

Secondary Outcome Measures

1. Relapse/Progression [Year 2]

   Relapse is defined as the appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size. Progression is defined as a lymph node with a diameter of the short axis of less than 1.0 cm must increase by >= 50% and to a size of 1.5 x 1.5 cm or more than 1.5 cm in the long axis.

2. Progression-Free Survival (PFS) [Year 2]

   The time to this event is the time from enrollment until death, relapse/progression, receipt of anti-lymphoma therapy, or last follow up, whichever comes first. Progression-free survival (PFS) will be estimated using the Kaplan Meier product limit estimator. The PFS probability and confidence interval will be calculated at two years post-transplant.

3. Complete Remission (CR) and/or Partial Response (PR) [Day 100]

   The frequencies and proportions of patients who have a CR or PR. CR is defined as the disappearance of all evidence of disease, and PR is defined as the regression of measurable disease and no new sites.

4. Time to Progression After CR [Year 2]

   This will be assessed in patients with CR. Patients are considered failure for this end point if they relapse after complete remission. Surviving patients with no history of relapse/progression are censored at time of last follow-up.

5. Lymphoma Disease-free Survival [Year 2]

   This will be assessed in patients with CR. Patients are considered failure for this end point if they die or if they relapse after complete remission. Patients with no history of relapse or death after complete remission are censored at time of last follow up.

6. Cumulative Incidence of Neutrophil Recovery [Day 28]

   Neutrophil recovery is defined as two consecutive days of absolute neutrophil count (ANC) > 500 neutrophils/μL following the expected nadir.

7. Cumulative Incidence of Platelet Recovery [Day 100]

   Platelet recovery is defined as a platelet count greater than 20,000/μL for the first of two consecutive labs with no platelet transfusions 7 days prior.

8. Hematologic Function [Days 100 and 365]

   Hematologic function will be defined as ANC > 1500 neutrophils/μL, Hemoglobin> 10g/dL without transfusion support, and platelets > 100,000/μL

9. Number of Participants Experiencing Toxicity [Year 2]

   Toxicities will be defined by using the version 3.0 NCI Common Terminology Criteria for Adverse Events (CTCAE) criteria. Only grade 3 and higher toxicities will be collected.

10. Number of Participants Experiencing Infections [Year 1]

    Microbiologically documented infections will be reported by site of disease, date of onset, severity, and resolution, if any.

11. Treatment-Related Mortality (TRM) [Day 100]

    TRM is defined as death occurring in a patient from causes other than relapse or progression. A cumulative incidence curve will be computed along with a 95% confidence interval at 100 days post-transplant.

12. Immunologic Reconstitution [Year 1]

    Immunologic Reconstitution will be assessed by quantitative immunoglobulin measurement (IgM, IgG and IgA)

13. HIV Single-Copy Polymerase Chain Reaction (PCR) [Baseline, Days 100, 180, 365, and 730]

    HIV RNA assay will be performed at the specified time points and summarize the assessments of the viral copy number using descriptive statistics.

14. Microbial Translocation Markers [Day 30 and 100]

    Level of microbial translocation markers will be determined by nonparametric Mann-Whitney tests comparing the distribution of prior microbial translocation markers between patients.

15. Ig and Epstein-Barr Virus (EBV) DNA in Blood [Day 100, 180, and 365]

    The presence of clonal Ig DNA in plasma will be assessed, as will EBV copy number in plasma and in peripheral blood

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of persistent or recurrent World Health Organization (WHO) classification diffuse large B-cell lymphoma, composite lymphoma with > 50% diffuse large B-cell lymphoma, mediastinal B-cell lymphoma, immunoblastic, plasmablastic, Burkitt's or Burkitt-like or classical Hodgkin's lymphoma. Patients transformed from follicular lymphoma are eligible for the study, pending fulfillment of other criteria.

• 15 years old or older

• Three or fewer prior regimens of chemotherapy over the entire course of their disease treatment (including one induction chemotherapy and no more than 2 salvage chemotherapies). Monoclonal antibody therapy and involved field radiation therapy will not be counted as prior therapies.

• All patients must have chemosensitive disease as demonstrated by at least a partial response to induction or salvage therapy.

• Less than or equal to 10% bone marrow involvement.

• Patients with adequate organ function as measured by: a)Cardiac: American Heart Association Class I: Patients with cardiac disease but without resulting limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea, or anginal pain. Additionally, all patients must have a left ventricular ejection fraction at rest greater than or equal to 40% demonstrated by Multi Gated Acquisition Scan (MUGA) or echocardiogram; b)Hepatic: (i) Bilirubin less than 2.0 mg/dL (except for isolated hyperbilirubinemia attributed to Gilbert syndrome or antiretroviral therapy) and alanine transaminase (ALT) and aspartate transaminase (AST) greater than 3x the upper limit of normal; (ii) Concomitant Hepatitis: Patients with chronic hepatitis B or C may be enrolled on the trial providing the above criteria are met. In addition, no active viral replication - undetectable (viral load less than 500 copies/ml) hepatitis B DNA level by PCR and no clinical or pathologic evidence of irreversible chronic liver disease; c)Renal: Creatinine clearance (calculated creatinine clearance is permitted) greater than 40 mL/min; d)Pulmonary: Carbon Monoxide Diffusing Capacity (DLCO), forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) greater than or equal to 45% of predicted (corrected for hemoglobin).

• Autologous peripheral stem cell graft with a minimum of greater than or less than 1.5 x 10^{6 CD 34+ cells/kg (target greater than or less than 2.0 x 10}6 CD 34+ cells/kg) or if peripheral blood stem cell (PBSC) mobilization fails, cells can be obtained by bone marrow harvest per institutional practices (in cases where bone marrow will be used for transplantation, the required CD34+ dose does not apply and institutional requirements for total nucleated cell dose should apply).

• Initiate conditioning therapy within 3 months of mobilization or bone marrow harvest.

• Signed informed consent.

• Patients on antiretroviral therapies (ARVs) can either have: a) Undetectable HIV viral load (VL less than 50 copies); b) If VL detectable at less than 2000 copies/mL must have review of previous antiretroviral regimens or previous genotypic or phenotypic testing which indicate the ability to fully suppress virus by addition of sensitive drugs. This review will be carried out by the Infectious Disease (ID) specialist caring for the patient; c)If VL detectable at greater than 2000 copies/mL, a current HIV genotype and/or phenotype must be obtained. If a HAART regimen to which the patient's virus is sensitive can be determined based on genotype and previous antiretroviral experience, then the patient will be considered eligible in this regard. This review will be carried out by the ID specialist caring for the patient.

Exclusion Criteria:

• Karnofsky performance score less than 70%.

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

• Prior malignancy in the 5 years prior to enrollment except resected basal cell carcinoma, treated cervical carcinoma in situ or Kaposi's sarcoma: a)Symptomatic Kaposi's sarcoma currently requiring therapy is excluded (patients receiving topical therapy for minimal disease are not included in this definition); b)Prior treatment with topical agents, local radiation, or up to 6 cycles of cytotoxic chemotherapy at least six months prior is permitted; c) Other cancers treated with curative intent less than 5 years previously will not be allowed unless approved by the Medical Monitor or Protocol Chair; d)Cancer treated with curative intent more than 5 years previously will be allowed.

• Pregnant (positive β-HCG) or breastfeeding.

• Fertile men or women unwilling to use contraceptive techniques from the time of initiation of mobilization until six-months post-transplant.

• Prior autologous or allogeneic HCT.

• Patients with evidence of Myelodysplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML) or abnormal cytogenetic analysis indicative of MDS on the pre-transplant bone marrow examination. Pathology report documentation need not be submitted.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope National Medical Center	Duarte	California	United States	91010-3000
2	University of California San Diego Medical Center	La Jolla	California	United States	92093
3	UCLA	Los Angeles	California	United States	90035
4	University of CA, SF	San Francisco	California	United States	94143
5	University of Florida College of Medicine	Gainesville	Florida	United States	32610
6	H. Lee Moffitt Cancer Center	Tampa	Florida	United States	33624
7	Emory University	Atlanta	Georgia	United States	30322
8	BMT Program at Northside Hospital	Atlanta	Georgia	United States	30342
9	University of Maryland Medical Systems, Greenebaum Cancer Center	Baltimore	Maryland	United States	21201
10	Johns Hopkins Medical Institution	Baltimore	Maryland	United States	21231
11	Washington University/Barnes Jewish Hospital	Saint Louis	Missouri	United States	63110
12	Weill Cornell Medical College	New York	New York	United States	10065
13	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10174
14	University of Rochester	Rochester	New York	United States	14642
15	Ohio State University Medical Center	Columbus	Ohio	United States	43210
16	University of Texas/MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• Medical College of Wisconsin
• National Heart, Lung, and Blood Institute (NHLBI)
• National Cancer Institute (NCI)
• Blood and Marrow Transplant Clinical Trials Network
• National Marrow Donor Program

Investigators

• Study Director: Mary Horowitz, MD, Center for International Blood and Marrow Transplant Research

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Blood and Marrow Transplant Clinical Trials Network Website
• National Marrow Donor Program

Publications

None provided.

• Responsible Party: Medical College of Wisconsin
• ClinicalTrials.gov Identifier: NCT01141712
• Other Study ID Numbers: BMTCTN0803; U01HL069294; U01HL069294-06; U01CA121947
• First Posted: Jun 10, 2010
• Last Update Posted: Jan 27, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Medical College of Wisconsin: HIV; B-cell Lymphoma; Burkitt's Lymphoma; Follicular Lymphoma; Hodgkin's Lymphoma
• Additional relevant MeSH terms: Lymphoma; Cytarabine; Etoposide; Melphalan; Carmustine

Study Results

Participant Flow

Recruitment Details	Participants were enrolled between April 2010 and March 2013 from 16 different transplant centers.
Pre-assignment Detail	Three patients did not undergo transplantation due to disease progression prior to conditioning.

Arm/Group Title	Autologous Transplant
Arm/Group Description	Patients will receive BCNU 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 twice a day from Days -5 to -2, Cytarabine 100 mg/m^2 twice a day from Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by autologous HCT.
Period Title: Overall Study
STARTED	43
COMPLETED	40
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Autologous Transplant
Arm/Group Description	Patients will receive BCNU 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 twice a day (BID) on Days -5 to -2, Cytarabine 100 mg/m^2 BID Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by autologous HCT.
Overall Participants	40
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	46.9
Sex: Female, Male (Count of Participants)
Female	5 12.5%
Male	35 87.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	9 22.5%
Not Hispanic or Latino	29 72.5%
Unknown or Not Reported	2 5%
Race/Ethnicity, Customized (participants) [Number]
Black or African American	13 32.5%
White	24 60%
Unknown	3 7.5%
Karnofsky Performance Score (participants) [Number]
100	11 27.5%
90	20 50%
80	7 17.5%
70	2 5%
Participant Diagnosis (participants) [Number]
Hodgkin's Lymphoma	15 37.5%
Diffuse Large B-cell Lymphoma	16 40%
Plasmablastic Lymphoma	2 5%
Burkitt's Lymphoma	7 17.5%
Disease Status (participants) [Number]
Complete Remission	30 75%
Partial Remission	9 22.5%
Relapsed or Progressive Disease	1 2.5%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	Assess the OS after autologous hematopoietic stem cell transplantation (HCT) for chemotherapy-sensitive aggressive B cell lymphoma or Hodgkin's lymphoma in patients with HIV using BEAM for pre-transplant conditioning. The primary analysis will consist of estimating the 1 year OS probability from the time of transplantation based on the Kaplan-Meier product limit estimator. The 1 year and 2 year OS and confidence interval will be calculated.
Time Frame	Year 1 and 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Autologous Transplant
Arm/Group Description	Patients will receive BCNU 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 BID Days -5 to -2, Cytarabine 100 mg/m^2 BID Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by autologous HCT.
Measure Participants	40
1 year	87.3 218.3%
2 years	82 205%

2. Secondary Outcome

Title	Relapse/Progression
Description	Relapse is defined as the appearance of any new lesion more than 1.5 cm in any axis during or at the end of therapy, even if other lesions are decreasing in size. Progression is defined as a lymph node with a diameter of the short axis of less than 1.0 cm must increase by >= 50% and to a size of 1.5 x 1.5 cm or more than 1.5 cm in the long axis.
Time Frame	Year 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Autologous Transplant
Arm/Group Description	Patients will receive BCNU 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 BID Days -5 to -2, Cytarabine 100 mg/m^2 BID Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by autologous HCT.
Measure Participants	40
Number (95% Confidence Interval) [percentage of participants]	12.5 31.3%

3. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	The time to this event is the time from enrollment until death, relapse/progression, receipt of anti-lymphoma therapy, or last follow up, whichever comes first. Progression-free survival (PFS) will be estimated using the Kaplan Meier product limit estimator. The PFS probability and confidence interval will be calculated at two years post-transplant.
Time Frame	Year 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Autologous Transplant
Arm/Group Description	Patients will receive BCNU 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 BID Days -5 to -2, Cytarabine 100 mg/m^2 BID Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by autologous HCT.
Measure Participants	40
Number (95% Confidence Interval) [percentage of participants]	79.8 199.5%

4. Secondary Outcome

Title	Complete Remission (CR) and/or Partial Response (PR)
Description	The frequencies and proportions of patients who have a CR or PR. CR is defined as the disappearance of all evidence of disease, and PR is defined as the regression of measurable disease and no new sites.
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

One participant died at day 64 and was not included in analysis

Arm/Group Title	Autologous Transplant
Arm/Group Description	Patients will receive BCNU 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 BID Days -5 to -2, Cytarabine 100 mg/m^2 BID Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by autologous HCT.
Measure Participants	39
CR	36 90%
PR	1 2.5%
Relapse/Progression	2 5%

5. Secondary Outcome

Title	Time to Progression After CR
Description	This will be assessed in patients with CR. Patients are considered failure for this end point if they relapse after complete remission. Surviving patients with no history of relapse/progression are censored at time of last follow-up.
Time Frame	Year 2

Outcome Measure Data

Analysis Population Description

No data collected to analyze this outcome measure

Arm/Group Title	Autologous Transplant
Arm/Group Description	Patients will receive BCNU 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 BID Days -5 to -2, Cytarabine 100 mg/m^2 BID Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by autologous HCT.
Measure Participants	0

6. Secondary Outcome

Title	Lymphoma Disease-free Survival
Description	This will be assessed in patients with CR. Patients are considered failure for this end point if they die or if they relapse after complete remission. Patients with no history of relapse or death after complete remission are censored at time of last follow up.
Time Frame	Year 2

Outcome Measure Data

Analysis Population Description

No data collected to analyze this outcome measure.

Arm/Group Title	Autologous Transplant
Arm/Group Description	Patients will receive BCNU 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 BID Days -5 to -2, Cytarabine 100 mg/m^2 BID Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by autologous HCT.
Measure Participants	0

7. Secondary Outcome

Title	Cumulative Incidence of Neutrophil Recovery
Description	Neutrophil recovery is defined as two consecutive days of absolute neutrophil count (ANC) > 500 neutrophils/μL following the expected nadir.
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Autologous Transplant
Arm/Group Description	Patients will receive BCNU 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 BID Days -5 to -2, Cytarabine 100 mg/m^2 BID Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by autologous HCT.
Measure Participants	40
Number (95% Confidence Interval) [percentage of participants]	97.5 243.8%

8. Secondary Outcome

Title	Cumulative Incidence of Platelet Recovery
Description	Platelet recovery is defined as a platelet count greater than 20,000/μL for the first of two consecutive labs with no platelet transfusions 7 days prior.
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Autologous Transplant
Arm/Group Description	Patients will receive BCNU 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 BID Days -5 to -2, Cytarabine 100 mg/m^2 BID Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by autologous HCT.
Measure Participants	40
Number (95% Confidence Interval) [percentage of participants]	92.5 231.3%

9. Secondary Outcome

Title	Hematologic Function
Description	Hematologic function will be defined as ANC > 1500 neutrophils/μL, Hemoglobin> 10g/dL without transfusion support, and platelets > 100,000/μL
Time Frame	Days 100 and 365

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Autologous Transplant
Arm/Group Description	Patients will receive BCNU 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 BID Days -5 to -2, Cytarabine 100 mg/m^2 BID Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by autologous HCT.
Measure Participants	40
Day 100	11 27.5%
Day 365	23 57.5%

10. Secondary Outcome

Title	Number of Participants Experiencing Toxicity
Description	Toxicities will be defined by using the version 3.0 NCI Common Terminology Criteria for Adverse Events (CTCAE) criteria. Only grade 3 and higher toxicities will be collected.
Time Frame	Year 2

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Autologous Transplant
Arm/Group Description	Patients will receive BCNU 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 BID Days -5 to -2, Cytarabine 100 mg/m^2 BID Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by autologous HCT.
Measure Participants	40
Number [participants]	9 22.5%

11. Secondary Outcome

Title	Number of Participants Experiencing Infections
Description	Microbiologically documented infections will be reported by site of disease, date of onset, severity, and resolution, if any.
Time Frame	Year 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Autologous Transplant
Arm/Group Description	Patients will receive BCNU 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 BID Days -5 to -2, Cytarabine 100 mg/m^2 BID Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by autologous HCT.
Measure Participants	40
Number [participants]	22 55%

12. Secondary Outcome

Title	Treatment-Related Mortality (TRM)
Description	TRM is defined as death occurring in a patient from causes other than relapse or progression. A cumulative incidence curve will be computed along with a 95% confidence interval at 100 days post-transplant.
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Autologous Transplant
Arm/Group Description	Patients will receive BCNU 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 BID Days -5 to -2, Cytarabine 100 mg/m^2 BID Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by autologous HCT.
Measure Participants	40
Number (95% Confidence Interval) [percentage of participants]	5.2 13%

13. Secondary Outcome

Title	Immunologic Reconstitution
Description	Immunologic Reconstitution will be assessed by quantitative immunoglobulin measurement (IgM, IgG and IgA)
Time Frame	Year 1

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Autologous Transplant
Arm/Group Description	Patients will receive BCNU 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 BID Days -5 to -2, Cytarabine 100 mg/m^2 BID Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by autologous HCT.
Measure Participants	40
IgG	1090
IgA	123
IgM	48.5

14. Secondary Outcome

Title	HIV Single-Copy Polymerase Chain Reaction (PCR)
Description	HIV RNA assay will be performed at the specified time points and summarize the assessments of the viral copy number using descriptive statistics.
Time Frame	Baseline, Days 100, 180, 365, and 730

Outcome Measure Data

Analysis Population Description

Participants with an undetectable (<50 copies/mL) viral load are not included in this analysis (Baseline = 32, Day 100 = 19, Day 180 = 20, Day 365 = 19, and Day 730 = 21)

Arm/Group Title	Autologous Transplant
Arm/Group Description	Patients will receive BCNU 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 BID Days -5 to -2, Cytarabine 100 mg/m^2 BID Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by autologous HCT.
Measure Participants	32
Baseline	80
Day 100	298
Day 180	84
Day 365	97
Day 730	130

15. Secondary Outcome

Title	Microbial Translocation Markers
Description	Level of microbial translocation markers will be determined by nonparametric Mann-Whitney tests comparing the distribution of prior microbial translocation markers between patients.
Time Frame	Day 30 and 100

Outcome Measure Data

Analysis Population Description

No data collected to analyze this outcome measure.

Arm/Group Title	Autologous Transplant
Arm/Group Description	Patients will receive BCNU 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 BID Days -5 to -2, Cytarabine 100 mg/m^2 BID Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by autologous HCT.
Measure Participants	0

16. Secondary Outcome

Title	Ig and Epstein-Barr Virus (EBV) DNA in Blood
Description	The presence of clonal Ig DNA in plasma will be assessed, as will EBV copy number in plasma and in peripheral blood
Time Frame	Day 100, 180, and 365

Outcome Measure Data

Analysis Population Description

No data collected to analyze this outcome measure.

Arm/Group Title	Autologous Transplant
Arm/Group Description	Patients will receive BCNU 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 BID Days -5 to -2, Cytarabine 100 mg/m^2 BID Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by autologous HCT.
Measure Participants	0

Adverse Events

Time Frame	2 years post-transplant
Adverse Event Reporting Description	Serious Adverse Events (AE) are defined as events associated with death, life-threatening event, disability, congenital anomaly, required intervention to prevent permanent impairment or damage, hospitalization or other serious adverse event. Only unexpected grades 3-5 adverse events were required to be reported through the AE system per protocol.
Arm/Group Title	Autologous Transplant
Arm/Group Description	Patients will receive BCNU 300 mg/m^2 Day -6, Etoposide 100 mg/m^2 BID Days -5 to -2, Cytarabine 100 mg/m^2 BID Days -5 to -2, and Melphalan 140 mg/m^2 Day -1 followed by autologous HCT.
All Cause Mortality
	Autologous Transplant
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Autologous Transplant
	Affected / at Risk (%)	# Events
Total	6/40 (15%)
Blood and lymphatic system disorders
Febrile neutropenia	1/40 (2.5%)	1
Cardiac disorders
Angina pectoris	1/40 (2.5%)	1
Gastrointestinal disorders
Odynophagia	1/40 (2.5%)	1
Infections and infestations
Septic shock	1/40 (2.5%)	1
Vascular disorders
Deep vein thrombosis	2/40 (5%)	2
Other (Not Including Serious) Adverse Events
	Autologous Transplant
	Affected / at Risk (%)	# Events
Total	3/40 (7.5%)
Infections and infestations
Appendicitis	1/40 (2.5%)	1
Metabolism and nutrition disorders
Hyperglycaemia	1/40 (2.5%)	1
Hypernatraemia	1/40 (2.5%)	1

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.