AzTrials
AzTrials

Lymphoma, Non-HodgkinPhase 2NCT00481832

Autologous Followed by Non-myeloablative Allogeneic Transplantation for Non-Hodgkin's Lymphoma

A Phase 2 study testing Cyclophosphamide, BCNU and Etoposide in people with 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
Search all trials

Trial summary

The purpose of this trial is to develop an alternative treatment for patients with poor risk non-Hodgkin's lymphoma. This trial uses a combination of high dose chemotherapy with stem cell transplant using the patient's own cells. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Lymphoma, Non-Hodgkin
What is being tested?
Cyclophosphamide, BCNU and Etoposide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteUnited States
Study dates
Jan 2007to 30 Mar 2017
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 non-Hodgkin's lymphoma
  • Relapse after achieving initial remission or failure to achieve initial remission.
  • KPS > 70%
  • Matched related or unrelated donor identified and available. Donor must be a complete match or have only a single allele mismatch.
  • Recent Bone marrow biopsy and cytogenetic analysis
Show all 12Show fewer
  • Patients must have a pretreatment serum bilirubin < 2 x the institutional ULN, a serum creatinine < 2 x the institutional ULN and measured or estimated creatinine clearance > 50 cc/min by the following formula (all tests must be performed within 28 days prior to mobilization ): Estimated Creatinine Clearance = (140 age) X WT(kg) X 0.85 if female 72 X serum creatinine(mg/dl).
  • Patients must have an EKG within 42 days prior to registration that shows no significant abnormalities that are suggestive of active cardiac disease.
  • Patients must have an echocardiogram or MUGA scan within 42 days of registration. If the ejection fraction is < 40%, the patient will not be eligible. If the ejection fraction is 40-50%, patients must have an exercise echocardiogram or dobutamine-echo with a normal response to exercise.
  • Patients must have a corrected diffusion capacity > 50% prior to the autologous transplant and > 40% prior to the allogeneic transplant.
  • Patients with known allergy to etoposide or a history of Grade 3 hemorrhagic cystitis with cyclophosphamide are not eligible.
  • Patients must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines.

Who cannot join

  • Pregnant or breast-feeding women are ineligible due to the known birth defects association with the treatments used in this study.
  • Patients known to be human immunodeficiency virus (HIV)-positive are ineligible because the concern for opportunistic infection and hematologic reserve are considered to be significantly greater in this population.
  • Patients with prior maligancies diagnosed > 5 years ago without evidence of disease are eligible. Patients with a prior malignancy treated < 5 years ago but have a life expectancy of > 5 years for that malignancy are eligible.
  • Patients with uncontrolled infection.
  • No prior autologous or allogeneic hematopoietic cell transplantation.
  • Donor Selection/Evaluation:
Show all 10Show fewer
  • 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.
  • Virology testing including CMV, HIV, EBV, HTLV, RPR, Hepatitis A, B and C will be performed within 30 days of donation.
  • No prior malignancy is allowed except adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer or other cancer for which the donor has been disease-free for five years

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

The purpose of this trial is to develop an alternative treatment for patients with poor risk non-Hodgkin's lymphoma. This trial uses a combination of high dose chemotherapy with stem cell transplant using the patient's own cells. This is followed with non-myeloablative transplant using stem cells from a related or unrelated donor to try and generate an anti-lymphoma response from the new immune system.

Read the detailed description

Currently, patients with recurrent or primary refractory non-Hodgkin's lymphoma are treated with second-line chemotherapy (usually 2-3 courses) for the purpose of cytoreduction and to establish sensitivity to chemotherapy. Thereafter, peripheral blood progenitor cells are mobilized with cyclophosphamide and granulocyte colony stimulating factor, apheresed and cryopreserved. The standard high dose regimen consists of augmented carmustine, etoposide and cyclophosphamide. Unfortunately, there are subgroups of patients with poor outcomes using autologous transplantation including those with transformed lymphoma as well as patients who do not attain a minimal disease state due to chemoresistant disease.

These groups of patients have limited disease control and survival with standard chemotherapy regimens, and although they often have excellent cytoreduction with the high-dose chemotherapy regimen, relapse remains the primary cause of treatment failure. The current trial utilizes a similar approach that has been taken with patients with multiple myeloma, who appear to benefit from an allogeneic graft-versus-tumor effect, using a combined autologous and non-myeloablative allogeneic transplant regimen to reduce transplant-related complications. Eligible patients will be treated with high-dose chemotherapy using BCNU, etoposide and cyclophosphamide with autologous hematopoietic cell support as a method of cytoreduction. Approximately 60-120 days after the autologous transplant, patients will receive an allogeneic transplant using a preparative regimen of total lymphoid irradiation and anti-thymocyte globulin in an attempt to develop a graft-versus-lymphoma effect.

Being tested
Cyclophosphamide, BCNU, Etoposide, Filgrastim, Antithymocyte globulin
Medical subject headings
Lymphoma, Non-Hodgkin

What participants receive

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

  • CyclophosphamideDrug

    Also called Cytoxan, Neosar

    4 gm /m² IV over 2 hours on day 8

  • BCNUDrug

    Also called BiCNU, Carmustine

    The dose of BCNU will be based on actual body weight unless the actual body weight is more than 15 kg greater than the ideal body weight in which case the adjusted ideal body weight will be used:

    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, VP-16

    60mg/kg, IV over 4 hours on day -4 pre-transplant and for preparative regimen. The dose of etoposide for mobilization is 2 gm/ m².

  • FilgrastimDrug

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

    10µg/kg sc qd starting day following cyclosphamide (or VP-16) until last day of apheresis

  • Antithymocyte globulinDrug

    Also called ATG

    1.5 mg/kg/d, IV from day -11 to -7

  • CyclosporineDrug

    Also called cyclosporin, cyclosporin A

    5mg/kgbid,variable, po or IV

  • Mycophenolate mofetilDrug

    Also called MMF, CellCep

    15 mg/kg po on day 0, at 5-10 hours after mobilized PBPC infusion is complete. Thereafter, beginning 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. Doses will be rounded up to the nearest 250 mg (capsules are 250 mg). MMF will be stopped on day +28 for matched related donors. For one antigen mismatched related or unrelated donors, the taper will begin on day +40. MMF will be tapered by 10% weekly till off, typically by day +96. If there is nausea and vomiting at any time preventing the oral administration of MMF, MMF should be administered intravenously at an equal dose. MMF dosing is based on actual body weight.

  • RituximabDrug

    Also called Rituxan, MabThera

    375 mg/m2 IV (calculated based on actual body weight) on day 1 and day 7. Administered per current standard of care..

  • 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 irradiationProcedure or surgery

    Also called TLI

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

  • CD34+ CellsDrug

    2 x 10e6 CD34+ cells per kg actual body weight on Day 0

  • Solu-MedrolDrug

    Also called Methylprednisolone

    1 mg/kg, Day-11 to Day-7

Study groups in NCT00481832
Study groupRoleWhat they receive
T & B Cell Mobilization Auto & Allo HCTExperimentalA transplant regimen that conditions the subjects using total lymphoid irradiation (TLI) and anti-thymocyte globulin(ATG) which will reduce acute graft-vs-host disease to negligible rates while maintaining the anti-tumor graft vs lymphoma GvL benefit. Along with TLI/ATG regiment; Solumedrol will be used as pre-medication and anti-emetic for any side effects. For stem cell mobilization, participants will be given either B Cell NLH or T Cell NHL. Before the filgrastim (G-CSF) mobilized PBPC infusion: acetaminophen, diphenhydramine and hydrocortisone will also be given as another set of pre-medications. BCNU, Etoposide, and Cyclophosphamide will be used as a preparative regimen. Cyclosporine and mycophenolate mofetil will be administered as an immunosuppressant after transplantation. Lastly, rituximab will be infused at the end of the transplantation regimen.
Receives: Drug: Cyclophosphamide; Drug: BCNU; Drug: Etoposide; Drug: Filgrastim; Drug: Antithymocyte globulin; Drug: Cyclosporine; Drug: Mycophenolate mofetil; Drug: Rituximab; Procedure: Autologous hematopoietic stem cell transplantation (auto-HSCT); Procedure: Allogeneic hematopoietic stem cell transplantation (allo-HSCT); Procedure: Total lymphoid irradiation; Drug: CD34+ Cells; Drug: Solu-Medrol

What is being measured

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

  1. Event-free Survival (EFS)

    Event-free survival (EFS) as determined for participants who receive both planned transplants, for a minimum of 3 years.

    Events are defined as "disease progression/relapse" and "death of all causes".

    Measured: 3 years

Secondary outcomes (9)

  1. Incidence of Chemotherapy-associated Pneumonitis

    Interstitial pneumonitis (IP) is a risk associated with high-dose carmustine (BCNU) or other chemotherapy drugs used for transplantation. IP is diagnosed by 1) a decrease of >25% in DLCO compared with pre-transplant PFT DLCO values or 2) a drop of 7% or more in oxygen saturation after exertion.

    Measured: 3 years

  2. Relapse Rate

    Relapse rate (disease recurrence) 3 years after transplant, for participants who received both transplants, as determined by Kaplan-Meier estimation.

    Measured: 3 years

  3. Overall Survival (OS)

    Overall Survival (OS) 3 years after transplant, for participants who received both transplants, as determined by Kaplan-Meier estimation.

    Measured: 3 years

  4. Incidence of Acute Graft Versus Host Disease (GvHD)

    The development of GvHD in vaccinated patients of any grade and at 6 months.

    Measured: 6 Months

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

    The development of GvHD in vaccinated patients of any grade at 6 months.

    Measured: 3 years

  6. Overall Mortality Rate

    Overall mortality is determined by Kaplan-Meier estimation. The overall morality rate is expressed as the percentage of patients who died for any reason, including disease-related death.

    Measured: 3 years

  7. Median Time to Neutrophile Engraftment

    Complete blood counts were measured daily after allogeneic transplant. Time to neutrophil engraftment is defined as the number of days it takes to reach an absolute neutrophils count (ANC) >500, counting from the day of transplant.

    Measured: up to 45 days

  8. Achieving Full Donor Chimerism

    Achieving full donor chimerism (donor T cells >95%): Blood was sent for donor cell percentage measured by short tandem repeat (STR) at post-transplant Day 30; Day 60; Day 90; Day 120; Day 180; Day 270; and Day 360. Full donor chimerism is defined as donor CD3+ cells > 95%.

    Measured: Up to 1 year

  9. Median Time to Platelet Engraftment

    Complete blood counts were measured daily after allogeneic transplant. Time to platelet engraftment is defined as the number of days it takes to reach platelet count >20,000, counting from the day of transplant.

    Measured: Up to 45 days

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 startJan 2007
  3. Primary completion27 Oct 2014
  4. Study completion30 Mar 2017

Why it stopped: Accrual Factor

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
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00481832
Sponsor's protocol ID
IRB-05730
Other IDs
97623, BMT185
Status last verified
Jan 2018
First submitted
31 May 2007
Last updated
14 Feb 2018
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cyclophosphamide, BCNU and Etoposide in people with 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 12 inclusion and 10 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 Feb 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 Feb 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) (time frame: 3 years). 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 NCT00481832.

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 Feb 2018.

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