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Lymphoma, B-cellPhase 2NCT00482053

Phase 2 Poor Risk DLBCL of TLI and ATG Followed by Matched Allogeneic HT as Consolidation to Autologous HCT

A Phase 2 study testing Autologous hematopoietic stem cell transplantation (auto-HSCT), Allogeneic hematopoietic stem cell transplantation (allo-HSCT) and Total lymphoid irradiation (TLI) in people with Lymphoma, B-cell and Lymphoma, Non-Hodgkin, run by Stanford University at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

The purpose of this study is to determine if double autologous then allogeneic hematopoietic cell transplant may offer an improved treatment option for patients with relapsed diffuse large B-cell lymphoma (DLBCL) who are not likely to be cured by the conventional transplantation regimen. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Autologous hematopoietic stem cell transplantation (auto-HSCT), Allogeneic hematopoietic stem cell transplantation (allo-HSCT) and Total lymphoid irradiation (TLI)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
Oct 2006to May 2010
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 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age 18 to 70 years.
  • Histologically-proven diffuse large B-cell lymphoma (DLBCL) by the World Health Organization (WHO) classification.
  • Relapse after achieving initial remission or failure to achieve initial remission. Patients with residual radiographic abnormalities after primary therapy are eligible if abnormalities are postive by fluorodeoxyglucose (FDG)-positron emission tomography (PET) (FDG-PET).
  • Receipt of 2 cycles of second-line therapy and FDG-PET positive per Stanford (central) review. FDG-PET to be done 2 weeks after cycle 2 of second line chemotherapy.
  • Eastern Cooperative Oncology Group (ECOG) performance status < 2
  • Matched related or unrelated donor identified and available
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  • Bone marrow biopsy and cytogenetic analysis within 8 weeks of registration
  • Pretreatment serum bilirubin < 2 x the institutional upper limit of normal (ULN)
  • Serum creatinine < 2 x the institutional ULN and measured or estimated creatinine clearance > 60 mL/min by the following formula (all tests must be performed within 28 days prior to registration):
  • Estimated Creatinine Clearance = (140 age) x weight (kg) x 0.85 if female 72 x serum creatinine (mg/dL).
  • EKG within 42 days prior to registration with no significant abnormalities suggestive of active cardiac disease
  • Patients must have a radionuclide ejection fraction within 42 days of registration. If the ejection fraction is < 40%, the patient will not be eligible. If the ejection fraction is 40-50%, the patient will have a cardiology consult.
  • Corrected diffusion capacity > 55%.
  • Sexually active males are advised to use an accepted and effective method of birth control
  • Women of child-bearing potential are advised to use an accepted and effective method of birth control
  • Patients must sign and give written informed consent in accordance with institutional and federal guidelines. Patients must be informed of the investigational nature of this study.

Who cannot join

  • Known allergy to etoposide or a history of Grade 3 hemorrhagic cystitis with cyclophosphamide
  • Greater than Grade 2 sensory or motor peripheral neuropathy from prior vinca alkaloid use
  • Requiring therapy for coronary artery disease, cardiomyopathy, dysrhythmia, or congestive heart failure
  • Known to be human immunodeficiency virus (HIV)-positive. The antibody test for HIV must be performed within 42 days of registration.
  • Prior chemotherapy other than corticosteroids administered within 2 weeks of the initiation of protocol therapy.
  • Prior malignancy, except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer or other cancer for which the patients has been disease-free for five years.
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  • Prior diagnosis of non-Hodgkin's lymphoma
  • Active infection requiring oral or intravenous antibiotics
  • Prior autologous or allogeneic hematopoietic cell transplantation
  • Prior radioimmunotherapy
  • Pregnant
  • Lactating
  • DONOR ELIGIBILITY
  • Related or unrelated HLA-identical donors who are in good health and have no contra-indication to donation
  • No contra-indication for the donor to collection by apheresis of mononuclear cells mobilized by G-CSF at a dose of 16 µg/kg of body weight.
  • Donors will be evaluated with a full history and physical examination.
  • Virology testing including HIV; cytomegalovirus (CMV); Epstein-Barr virus (EBV); human T-lymphotropic virus (HTLV); rapid plasma reagin (RPR); Hepatitis A, B and C be performed within 30 days of donation.
  • Prospective donors will be screened for CMV seroreactivity and seronegative donors will be utilized if available.
  • If more than one human leukocyte antigen (HLA)-matched related donor exists, then the donor will be selected on the basis of CD31 allotype.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • Stanford University School of Medicine

    Stanford, California, 94305

Other trials in United States

About this study

Official title: A Phase 2 Study in Poor Risk Diffuse Large B-cell Lymphoma of Total Lymphoid Irradiation & Antithymocyte Globulin Followed by Matched Allogeneic Hematopoietic Transplantation as Consolidation to Autologous Hematopoietic Cell Transplantation

The purpose of this study is to determine if double autologous then allogeneic hematopoietic cell transplant may offer an improved treatment option for patients with relapsed diffuse large B-cell lymphoma (DLBCL) who are not likely to be cured by the conventional transplantation regimen.

Read the detailed description

This study tests a tandem transplant approach that starts with transplantation of the participant's own hematopoietic (blood) cells, eg, autologous hematopoietic cell transplant (auto-HCT) as preparation for an subsequent matched-donor allogeneic HCT (allo-HCT).

Participants will be have progenitor cells (stem cells) mobilized into the peripheral blood with rituximab, chemotherapy (cyclophosphamide or etoposide), and filgrastim (G-CSF); undergo apheresis to collect autologous peripheral blood stem cells (PBSC, aka hematopoietic cells); and be re-infused with ≥ 3 x 10e6 CD34+ cells/kg (auto-HCT). Subsequently, participants will receive therapeutic, non-myeloablative chemotherapy (carmustine + cyclophosphamide + etoposide), then transplant conditioning [total lymphoid irradiation (TLI) + anti-thymocyte globulin (ATG)] followed by ≥ 2 x 10e6 CD34+ cells/kg allogeneic PBSC obtained from a human leukocyte antigen (HLA)-matched or HLA single allele / antigen-mismatched donor (allo-HCT). Donors will be mobilized with 16 µg/kg filgrastim. Participant allo-HCT transplant is to occur within 150 days of auto-HCT. Post-allo-HCT infusion treatment includes cyclosporine and mycophenolate mofetil (MMF)

Subject's participation ends if a suitable matched donor is not identified within the 150 days.

Pre-medication treatments administered during this study may include acetaminophen; diphenhydramine; hydrocortisone; and methylprednisolone.

Being tested
Autologous hematopoietic stem cell transplantation (auto-HSCT), Allogeneic hematopoietic stem cell transplantation (allo-HSCT), Total lymphoid irradiation (TLI), Rituximab, Carmustine
Medical subject headings
Lymphoma, B-Cell, Lymphoma, Non-Hodgkin, Lymphoma, Large B-Cell, Diffuse

What participants receive

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

  • Autologous hematopoietic stem cell transplantation (auto-HSCT)Procedure or surgery

    Also called Autologous peripheral blood progenitor cell (PBPC) transplantation

    Auto-HCT involves an intravenous infusion of a participant's previously collected and frozen white blood cells collected after treatment with mobilizing agents

  • Allogeneic hematopoietic stem cell transplantation (allo-HSCT)Procedure or surgery

    Also called Allogeneic peripheral blood progenitor cell (PBPC) transplantation

    Allo-HCT involves an intravenous infusion of a donor's white blood cells collected after treatment with mobilization with filgrastim (G-CSF)

  • Total lymphoid irradiation (TLI)Procedure or surgery

    TLI is administered in 80cGy fractions on Days -11 to Day-7 relative to allo-HSCT

  • RituximabDrug

    Also called Rituxan, Mabthera

    375 mg/m2 IV days 1 and 7 over 4 to 8 hours

  • CarmustineDrug

    Also called BCNU, BiCNU

    Based on body weight, unless its more than 15 kg greater than the idal body 15mg/kg (max dose 550 mg/m2) day -6 over 2 hours.

    Males IBW = 50 kg + 2.3 kg/inch over 5 feet Females IBW = 45.5 kg + 2.3 kg/inch over 5 feet Adjusted IBW = IBW + 50% (actual weight - IBW)

  • EtoposideDrug

    Also called Eposin, Etopophos, Vepesid, VP-16

    60 mg/kg over 4 hours day -4 and alternatively VP-16 2 Gm/m² may be used (for mobilization)

  • FilgrastimDrug

    Also called Granulocyte colony-stimulating factor (G-CSF, GCSF), Colony-stimulating factor 3 (CSF-3)

    10 µg/kg/day subcutaneous starting Day 9 until last day of apheresis. 5 ug/kg actual body weight per day will be started at Day +6 after allo-HCT until hematologic recovery

  • Anti-thymocyte globulin (ATG)Drug

    1.5 mg/kg/day for 5 days

  • CyclosporineDrug

    Also called Cyclosporin, CSP

    5.0 mg/kg twice daily from day -3 until after day +56

  • Mycophenolate mofetil (MMF)Drug

    Also called CellCept

    250 mg (total) twice daily, oral

    15 mg/kg po on day 0, at 5-10 hours after mobilized PBPC infusion is complete. On day +1 MMF is taken at 15 mg/kg po b.i.d. (30 mg/kg/day) if transplantation was using a matched related donor and 15 mg/kg po t.i.d if from a matched unrelated donor or a one antigen mismatched donor.

  • CyclophosphamideDrug

    Also called Cytoxan, Neosar

    100 mg/kg will be administered over 2 hours on day -2

  • AcetaminophenDrug

    Also called Tylenol

    Pre-medication for rituximab and PBPC infusion. Administered at 650 mg by mouth 1 hour prior to infusion

  • DiphenhydramineDrug

    Also called Benadryl

    Pre-medication for rituximab and PBPC infusion. Administered at 50 mg intravenous 1 hour prior to infusion

  • HydrocortisoneDrug

    Also called Cortef

    Pre-medication for the PBPC infusion. Administered at 100 mg intravenous 1 hour prior to infusion

  • MethylprednisoloneDrug

    Also called Solu-Medrol

    Anti-reaction medication for the ATG infusion. Administered at 1 mg/kg, Day-11 to Day-7

Study groups in NCT00482053
Study groupRoleWhat they receive
Auto-HCT followed by Allo-HCT for Poor-risk DLBCLExperimentalParticipants will have peripheral blood stem cells (PBSC, aka progenitor / stem cells) mobilized to peripheral blood with rituximab, chemotherapy (cyclophosphamide or etoposide), and filgrastim; undergo apheresis to collect (self/autologous PBSC), and receive carmustine, etoposide, and cyclophosphamide as conditioning for PBSC infusion as a hematopoietic cell transplant (auto-HCT). Then participants will receive allogeneic HCT (allo-HCT) transplant conditioning [total lymphoid irradiation (TLI) + anti-thymocyte globulin (ATG)] followed by allogenic PBSC (allo-HCT) obtained from a human leukocyte antigen (HLA)-matched or single mismatch filgrastim-mobilized donor. Participant allo-HCT transplant is to occur within 150 days of auto-HCT. Post-allo-HCT treatment includes cyclosporine + mycophenolate mofetil (MMF). Subject's participation ends if donor is not identified within 150 days. Pre-medication includes acetaminophen; diphenhydramine; hydrocortisone; \& methylprednisolone.
Receives: Procedure: Autologous hematopoietic stem cell transplantation (auto-HSCT); Procedure: Allogeneic hematopoietic stem cell transplantation (allo-HSCT); Procedure: Total lymphoid irradiation (TLI); Drug: Rituximab; Drug: Carmustine; Drug: Etoposide; Drug: Filgrastim; Drug: Anti-thymocyte globulin (ATG); Drug: Cyclosporine; Drug: Mycophenolate mofetil (MMF); Drug: Cyclophosphamide; Drug: Acetaminophen; Drug: Diphenhydramine; Drug: Hydrocortisone; Drug: Methylprednisolone

What is being measured

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

  1. Event-free Survival (EFS) Per Protocol

    Event-free survival (EFS) through 4 years, as assessed in participants with poor-risk recurrent or primary refractory DLBCL treated with TLI and ATG followed by matched allogeneic hematopoietic cell transplantation as a consolidation to HCT. Event is defined as tumor progression or death.

    Measured: 48 months

Secondary outcomes (6)
  1. Median Time to Neutrophil Engraftment After Autologous Transplant

    Reported as neutrophil engraftment after autologous transplant, defined as absolute neutrophil count (ANC) > 500/µL, counting from the day of transplant.

    Measured: within 1 month

  2. Median Time to Platelet Engraftment After Autologous Transplant

    Reported as platelet engraftment after autologous transplant, defined as platelet count > 20,000/µL, counting from the day of transplant.

    Measured: within 1 month

  3. Median Time to Neutrophil Engraftment After Allogeneic Transplant

    Reported as neutrophil engraftment after allogeneic transplant, defined as absolute neutrophil count (ANC) > 500/µL, counting from the day of transplant.

    Measured: within 1 month

  4. Median Time to Platelet Engraftment After Allogeneic Transplant

    Reported as platelet engraftment after allogeneic transplant, defined as platelet count > 20,000/µL, counting from the day of transplant.

    Measured: within 1 month

  5. Incidence of Chronic Graft vs Host Disease (GvHD)

    The incidence of chronic graft vs host disease (GvHD) is reported as any events within 3 years. Note that GvHD was assessed per investigator judgement. There was no protocol-specified criteria of GvHD.

    Measured: 3 years

  6. Overall Survival (OS)

    To evaluate the overall and transplant related mortality rate, reported as the number of subjects remaining alive 3 years after transplant.

    Measured: 3 years

Timeline

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

  1. First posted4 Jun 2007 (estimated)
  2. Study startOct 2006
  3. Primary completionMay 2010
  4. Study completionMay 2010

Why it stopped: Low accrual

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
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00482053
Sponsor's protocol ID
IRB-06703
Other IDs
97355, BMT186
Status last verified
May 2018
First submitted
31 May 2007
Last updated
14 May 2018
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Autologous hematopoietic stem cell transplantation (auto-HSCT), Allogeneic hematopoietic stem cell transplantation (allo-HSCT) and Total lymphoid irradiation (TLI) in people with Lymphoma, B-cell and Lymphoma, Non-Hodgkin, run by Stanford University at 1 site 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 16 inclusion and 19 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: stopped early, as of the sponsor's last update on 14 May 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 14 May 2018). 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?

Event-free Survival (EFS) Per Protocol (time frame: 48 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 14 May 2018.

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