AzTrials
AzTrials

LymphomaPhase 2NCT01141712

Autologous Transplant in HIV Patients (BMT CTN 0803)

A Phase 2 study testing Autologous transplant, BCNU and Etoposide in people with Lymphoma and HIV, run by Medical College of Wisconsin at 16 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 15 years and older
Conditions the study is for
Lymphoma, HIV
What is being tested?
Autologous transplant, BCNU and Etoposide
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
16 sitesUnited States
Study dates
Apr 2010to Jun 2016
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 15 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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).
Show all 10Show fewer
  • 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.

Who cannot join

  • 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.

Trial locations and contacts

16 sites in 1 country.

16 sites in 1 country

United States16 sites

  • Emory University

    Atlanta, Georgia, 30322

  • BMT Program at Northside Hospital

    Atlanta, Georgia, 30342

  • University of Maryland Medical Systems, Greenebaum Cancer Center

    Baltimore, Maryland, 21201

  • Johns Hopkins Medical Institution

    Baltimore, Maryland, 21231

  • Ohio State University Medical Center

    Columbus, Ohio, 43210

  • City of Hope National Medical Center

    Duarte, California, 91010-3000

  • University of Florida College of Medicine

    Gainesville, Florida, 32610

  • University of Texas/MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of California San Diego Medical Center

    La Jolla, California, 92093

  • UCLA

    Los Angeles, California, 90035

  • Weill Cornell Medical College

    New York, New York, 10065

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10174

  • University of Rochester

    Rochester, New York, 14642

  • University of CA, SF

    San Francisco, California, 94143

  • Washington University/Barnes Jewish Hospital

    St Louis, Missouri, 63110

  • H. Lee Moffitt Cancer Center

    Tampa, Florida, 33624

Other trials in United States

About this study

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)

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.

Read the 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).

Conditions
Lymphoma, HIV
Being tested
Autologous transplant, BCNU, Etoposide, Cytarabine, Melphalan
Keywords
HIV, B-cell Lymphoma, Burkitt's Lymphoma, Follicular Lymphoma, Hodgkin's Lymphoma
Medical subject headings
Lymphoma, Lymphoma, B-Cell, Burkitt Lymphoma, Lymphoma, Follicular, Hodgkin Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Autologous transplantProcedure or surgery

    Participants will receive the BEAM conditioning regimen followed by autologous HCT.

  • BCNUDrug

    Also called Carmustine

    Participants will receive BCNU 300 mg/m^2 Day -6

  • EtoposideDrug

    Also called VP-16

    Participants will receive Etoposide 100 mg/m^2 BID Days -5 to -2

  • CytarabineDrug

    Also called Depocyt

    Participants will receive Cytarabine 100 mg/m^2 BID Days -5 to -2

  • MelphalanDrug

    Also called Alkeran

    Participants will receive Melphalan 140 mg/m^2 Day -1

Study groups in NCT01141712
Study groupRoleWhat they receive
Autologous transplantOtherPatients 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.
Receives: Procedure: Autologous transplant; Drug: BCNU; Drug: Etoposide; Drug: Cytarabine; Drug: Melphalan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Survival (OS)

    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.

    Measured: Year 1 and 2

Secondary outcomes (15)

  1. Relapse/Progression

    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.

    Measured: Year 2

  2. Progression-Free Survival (PFS)

    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.

    Measured: Year 2

  3. Complete Remission (CR) and/or Partial Response (PR)

    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.

    Measured: Day 100

  4. Time to Progression After CR

    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.

    Measured: Year 2

  5. Lymphoma Disease-free Survival

    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.

    Measured: Year 2

  6. Cumulative Incidence of Neutrophil Recovery

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

    Measured: Day 28

  7. Cumulative Incidence of Platelet Recovery

    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.

    Measured: Day 100

  8. Hematologic Function

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

    Measured: Days 100 and 365

  9. Number of Participants Experiencing Toxicity

    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.

    Measured: Year 2

  10. Number of Participants Experiencing Infections

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

    Measured: Year 1

  11. Treatment-Related Mortality (TRM)

    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.

    Measured: Day 100

  12. Immunologic Reconstitution

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

    Measured: Year 1

  13. HIV Single-Copy Polymerase Chain Reaction (PCR)

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

    Measured: Baseline, Days 100, 180, 365, and 730

  14. Microbial Translocation Markers

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

    Measured: Day 30 and 100

  15. Ig and Epstein-Barr Virus (EBV) DNA in Blood

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

    Measured: Day 100, 180, and 365

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jun 2010 (estimated)
  2. Study startApr 2010
  3. Primary completionMay 2015
  4. Study completionJun 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01141712
Sponsor's protocol ID
BMTCTN0803
Other IDs
U01HL069294, U01HL069294-06, U01CA121947
Status last verified
Dec 2022
First submitted
9 Jun 2010
Last updated
4 Jan 2023
Data monitoring committee
Yes
Individual data sharing
Yes: Findings will be published in a manuscript

Publications

  • Alvarnas JC, Le Rademacher J, Wang Y, Little RF, Akpek G, Ayala E, Devine S, Baiocchi R, Lozanski G, Kaplan L, Noy A, Popat U, Hsu J, Morris LE Jr, Thompson J, Horowitz MM, Mendizabal A, Levine A, Krishnan A, Forman SJ, Navarro WH, Ambinder R. Autologous hematopoietic cell transplantation for HIV-related lymphoma: results of the BMT CTN 0803/AMC 071 trial. Blood. 2016 Aug 25;128(8):1050-8. doi: 10.1182/blood-2015-08-664706. Epub 2016 Jun 13.

    PubMed 27297790

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Autologous transplant, BCNU and Etoposide in people with Lymphoma and HIV, run by Medical College of Wisconsin at 16 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 16 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall Survival (OS) (time frame: Year 1 and 2). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01141712, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jan 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in