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Diffuse, Large B-Cell, LymphomaPhase 2NCT01181271

Tandem Auto-Allo Transplant for Lymphoma

A Phase 2 study testing Busulfan (conditioning for AUTO transplant), Etoposide (conditioning for AUTO transplant) and Cyclophosphamide (conditioning for AUTO transplant) in people with Diffuse, Large B-Cell, Lymphoma and Lymphoma, Low-Grade, run by Massachusetts General Hospital at 2 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

Relapse remains a principle cause of treatment failure for patients with aggressive lymphoma after autologous transplantation. Non-myeloablative allogeneic transplantation allows patients to receive an infusion of donor cells in an attempt to induce a graft versus lymphoma effect. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Busulfan (conditioning for AUTO transplant), Etoposide (conditioning for AUTO transplant) and Cyclophosphamide (conditioning for AUTO transplant)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
42 participants
Where
2 sitesUnited States
Study dates
Aug 2010to Feb 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 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients with high-risk diffuse large B cell or transformed low grade lymphoma defined as:
  • Residual disease after at least 6 cycles of anthracycline-based chemotherapy (with residual disease defined as persistent bone marrow involvement and/or persistent measurable lymph node or solid organ masses that are PET or gallium avid)
  • Progressive disease after at least 2 cycles of anthracycline-based chemotherapy
  • Patients with an initial complete response but subsequent relapse within 6 months after completion of anthracycline-based chemotherapy
  • Patients with any T-cell non-Hodgkin's lymphoma as defined as:
  • Peripheral T-cell lymphoma (ALK negative PTCL-U) including PTCL-NOS, HSGD (hepato-splenic gamma-delta TCL), AITL (angioimmunoblastic T-cell lymphoma), EATL (enteropathy associated T-cell lymphoma), ALK-negative anaplastic large cell lymphoma
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  • Any T-cell histology (except LGL) with residual disease after at least 4 cycles of anthracycline-based chemotherapy (with residual disease defined as persistent bone marrow involvement and/or persistent measurable lymph node or solid organ masses that are PET or gallium avid)
  • Patients with mantle cell lymphoma at any time in therapy
  • Patients with "double-hit" lymphoma as characterized by the presence of concurrent overexpression of Bcl-2 and c-myc
  • Patients with Hodgkin's lymphoma that is
  • Refractory to first-line therapy and at least one second line chemotherapy regimen
  • Relapsed Hodgkin's lymphoma which is refractory to at least one salvage chemotherapy regimen.
  • Patients with CLL/SLL with 17p- cytogenetic abnormality
  • Age 18 years and greater
  • ECOG performance status 0-2
  • Ability to understand and the willingness to sign a written informed consent document.
  • Responsive disease to last therapy as determined by at least one of the following:
  • At least PR by Revised Response Criteria
  • At least PR by traditional Cheson Criteria
  • < 10% of overall cellularity involved with disease on bone marrow biopsy for patients with involvement of the bone marrow
  • Minimum of 2 x 106 CD34+ cells / kg already collected and frozen. These stem cells may have been collected from PBSC pheresis, bone marrow harvest, or the combination.

Who cannot join

  • Patients will be re-evaluated after autologous transplant prior to proceeding to non-myeloablative transplant
  • Pregnancy
  • Evidence of HIV infection
  • Heart failure uncontrolled by medications or ejection fraction less than 45%
  • Active involvement of the CNS by lymphoma
  • Inability to provide informed consent
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  • Previous autologous or allogeneic stem cell transplant
  • Creatinine greater than 2 gm/dL or 24 hour urine creatinine clearance < 50 cc/minute (does not have to satisfy both)
  • Total bilirubin greater than 2 times the upper limit of normal except when due to Gilbert's syndrome or hemolysis.
  • Transaminases greater than 3 times the upper limit of normal
  • FVC or DLCO of less than 50% of predicted (DLCO corrected for hemoglobin level)
  • Already known to not possess suitably HLA-matched related or unrelated donor
  • Eligibility to proceed to allogeneic transplant Cannot be admitted for allogeneic transplant earlier than 40 days and no later than 180 days after autologous stem cell transplant.
  • HLA identical (A, B, C and DR) related or unrelated donor available. HLA typing of class I loci (HLA- A, B, C) will be based on complement dependent cytotoxicity assay or PCR of sequence specific oligonucleotide primers (SSOP). Typing of HLA class II (DRB1) will be based on PCR of sequence specific oligonucleotide primers (SSOP).
  • No need for intravenous hydration in the previous 2 weeks
  • Resolved mucositis
  • Renal, cardiac, pulmonary, and hepatic function meet standard criteria for nonmyeloablative SCT as listed below:
  • Serum Cr < 2 gm/dL
  • LV ejection fraction > 30% and no uncontrolled symptoms of congestive heart failure
  • DLCO > 50% of predicted value (corrected for hemoglobin)
  • Transaminases < 5X the institution upper limit of normal
  • Bilirubin < 3X the institution upper limit of normal except when Gilbert's Syndrome or hemolysis is present
  • ECOG PS ≤ 2
  • No intravenous antimicrobials within 2 weeks
  • No evidence of progressive disease, defined as a 25% increase from nadir in the sum of the product of the diameters (SPD) of any lymph node previously identified as abnormal prior to autologous transplant or the appearance of any new lymph node greater than 1.5 cm in greatest diameter, new bone marrow involvement, or new solid organ nodule greater than 1 cm in diameter. This restaging study will be performed at least 28 days after the autologous transplant and within 60 days prior to admission for allogeneic transplant. Status of stable disease (SD) is acceptable to proceed to allogeneic transplant.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

Other trials in United States

About this study

Official title: Sequential Myeloablative Autologous Stem Cell Transplantation Followed by Allogeneic Non-Myeloablative Stem Cell Transplantation for Patients With Poor Risk Lymphomas

Relapse remains a principle cause of treatment failure for patients with aggressive lymphoma after autologous transplantation. Non-myeloablative allogeneic transplantation allows patients to receive an infusion of donor cells in an attempt to induce a graft versus lymphoma effect. This study will assess the feasibility, safety and efficacy of the combination of autologous stem cell transplantation followed by non-myeloablative transplantation for patients with poor-risk aggressive lymphoma.

Read the detailed description

This is a phase II clinical trial investigating the feasibility, and efficacy of sequential autologous stem cell transplant followed by non-myeloablative allogeneic transplant for patients with poor risk lymphoma. Patients will be enrolled onto the trial when eligible and undergo standard high-dose chemotherapy with the combination with busulfan, cyclophosphamide, and etoposide followed by autologous stem cell transplant. After recovery of counts and clinical status, patients will then proceed to non-myeloablative allogeneic stem cell transplant using a fully matched related or unrelated donor.

Being tested
Busulfan (conditioning for AUTO transplant), Etoposide (conditioning for AUTO transplant), Cyclophosphamide (conditioning for AUTO transplant), Mesna (prior to AUTO transplant), autologous (auto) peripheral blood stem cell transplantation
Keywords
Lymphoma, non-hodgkins lymphoma, Hodgkin's lymphoma, Hodgkin's disease, stem cell transplant, High-risk diffuse large B cell, Transformed low grade lymphoma, T-cell non-Hodgkin's lymphoma, Mantle cell lymphoma at any time in therapy, "Double-hit" lymphoma
Medical subject headings
Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Lymphoma, T-Cell, Lymphoma, Mantle-Cell, Hodgkin Disease, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma

What participants receive

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

  • Busulfan (conditioning for AUTO transplant)Drug

    Also called Busulfex

    0.8 mg/kg intravenous (IV) bolus every six hours (Q6H) on days -8,-7,-6,-5 (total of 14 doses). The total daily dose of busulfan will be 3.2 mg/kg on days -8,-7, and -6 and 1.6 mg/kg on day -5

  • Etoposide (conditioning for AUTO transplant)Drug

    Also called VP-16

    Etoposide 30 mg/kg IV bolus every day (QD) on day -4. The total daily dose of etoposide will be 30 mg/kg.

  • Cyclophosphamide (conditioning for AUTO transplant)Drug

    Also called Cytoxan

    Cyclophosphamide 60 mg/kg IV bolus QD on days -3 and -2. The total daily dose of cyclophosphamide will be 60 mg/kg.

  • Mesna (prior to AUTO transplant)Drug

    Mesna 15 mg/kg IV bolus on days -3 and -2 infused over 15 minutes and given 15 minutes prior to cyclophosphamide administration. This is followed by Mesna given 15 mg/kg IV bolus three times daily (TID) on days -3 and -2 infused over 15 minutes at 3, 6, and 9 hours after completion of cyclophosphamide infusion. Total daily dose of Mesna should be equivalent to daily dose of cyclophosphamide. Lastly, Mesna will be given at 15 mg/kg IV bolus QD on day -1. This makes a total of 9 doses of Mesna

  • autologous (auto) peripheral blood stem cell transplantationOther

    Infusion of autologous peripheral blood stem cells on Day 0.

  • NeupogenDrug

    Also called G-CSF

    Neupogen 5 mcg/kg subcutaneous (SQ) daily starting on day +1 until absolute neutrophil count (ANC) is greater than or equal to 1000 per micro liter on two separate occasions or greater than 5000 per micro liter once

  • Fludarabine (conditioning for ALLO Transplant)Drug

    Also called Fludara

    Fludarabine 30 mg/m2/day will be administered as a bolus infusion over approximately 30 minutes for 4 days on days -5, -4, -3, -2.

  • Busulfan (conditioning for ALLO Transplant)Drug

    Also called Busulfex

    Busulfan will be administered by IV infusion over approximately 3 hours on days -5, -4, -3, -2. The dose of busulfan will be 0.8 mg/kg/day

  • non-myeloablative allogeneic (allo) transplantOther

    Donor peripheral blood stem cells (PBSC) will be infused intravenously beginning on Day 0. The minimum total CD34+ cell dose will be 2 x 10^6 CD34+cells/kg of recipient's actual body weight with a maximum dose of 8 x 10^6/kg of recipient's actual body weight

  • TacrolimusDrug

    Also called FK506

    Tacrolimus (FK506) will be given orally at a dose of 0.05 mg/kg orally (PO) twice a day (BID) starting day -3.

  • SirolimusDrug

    Also called Rapamycin

    Sirolimus (rapamycin) will be given orally at a dose of 12 mg times one on day -3 and then the dose shall be 4 mg by mouth daily starting on day -2. The dose may then be adjusted according to serum levels at the discretion of the treating physician

  • MethotrexateDrug

    Methotrexate will be administered once daily on days 1, 3, and 6 as an IV bolus over 15 minutes at a dose of 5 mg/m2

Study groups in NCT01181271
Study groupRoleWhat they receive
Autologous then Allogeneic transplantExperimentalAll patients will receive conditioning with busulfan, etoposide, and cyclophosphamide (with mesna) and then will undergo autologous (auto) peripheral blood stem cell transplantation. Patients will be re-evaluated after autologous transplant prior to proceeding to non-myeloablative allogeneic (allo) transplant. If eligible to proceed, allogenic transplantation will take place no earlier than 40 days and no later than 180 days after autologous stem cell transplantation. Conditioning for the allogeneic transplant will consist of fludarabine and busulfan. Participants will receive tacrolimus and sirolimus as prophylaxis against graft versus host disease (GVHD).
Receives: Drug: Busulfan (conditioning for AUTO transplant); Drug: Etoposide (conditioning for AUTO transplant); Drug: Cyclophosphamide (conditioning for AUTO transplant); Drug: Mesna (prior to AUTO transplant); Other: autologous (auto) peripheral blood stem cell transplantation; Drug: Neupogen; Drug: Fludarabine (conditioning for ALLO Transplant); Drug: Busulfan (conditioning for ALLO Transplant); Other: non-myeloablative allogeneic (allo) transplant; Drug: Tacrolimus; Drug: Sirolimus; Drug: Methotrexate

What is being measured

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

  1. Peripheral Blood All-cell Donor Chimerism

    Successful donor stem cell engraftment is defined as when ≥ 80% of hematopoietic elements are donor-derived as determined by chimerism assays from peripheral blood at day 100 after non-myeloablative allogeneic stem cell transplantation.

    Measured: 100 days post allogeneic transplant

Secondary outcomes (11)

  1. Number of Days After Allogeneic Transplant Until Absolute Neutrophil Count Was Equal to or Greater Than 500/uL

    Measured: within 28 days after allogeneic transplant

  2. Cumulative Incidence of Grades II to IV Acute Graft Versus Host Disease (GVHD)

    Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.

    Measured: within 200 days after allogeneic transplant

  3. Cumulative Incidence of Extensive Chronic Graft-versus-host-disease

    Extensive chronic graft versus-host-disease (GVHD) was defined as GVHD that required systemic immunosuppression.

    Measured: 1-year after allogeneic transplant

  4. Cumulative Incidence of Non-relapse Mortality

    Non-relapse mortality is defined as participants who die from causes other than their underlying disease relapse, such as infection or graft versus host disease

    Measured: 2-years after allogeneic transplant

  5. Cumulative Incidence of Disease Relapse

    Measured: 2-years after allogeneic transplant

  6. Estimated Two Year Progression Free Survival Rate for Participants Undergoing Both Autologous and Allogeneic Transplants

    Measured: 2 years after allogeneic transplant

  7. Estimated Two Year Overall Survival Rate for Participants Undergoing Both Autologous and Allogeneic Transplants

    Measured: Two-years after Allogeneic Transplant

  8. Estimated Two Year Progression Free Survival Rate for All Participants

    Measured: 2 years

  9. Estimated Two Year Overall Survival Rate for All Participants

    Measured: 2 years

  10. Estimated Two Year Progression Free Survival Rate for Participants Undergoing Only Autologous Transplant

    Measured: Two Years

  11. Estimated Two Year Overall Survival Rate for Participants Undergoing Only Autologous Transplant

    Measured: two years

Timeline

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

  1. First posted13 Aug 2010 (estimated)
  2. Study startAug 2010
  3. Primary completionFeb 2014
  4. Study completionFeb 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
42 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01181271
Sponsor's protocol ID
10-057
Status last verified
Jan 2017
First submitted
12 Aug 2010
Last updated
9 Mar 2017
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Chen YB, Li S, Fisher DC, Driscoll J, Del Rio C, Abramson J, Armand P, Barnes J, Brown J, Cutler C, El-Jawahri A, Ho VT, Hochberg E, McAfee S, Takvorian R, Spitzer TR, Antin JH, Soiffer R, Jacobsen E. Phase II Trial of Tandem High-Dose Chemotherapy with Autologous Stem Cell Transplantation Followed by Reduced-Intensity Allogeneic Stem Cell Transplantation for Patients with High-Risk Lymphoma. Biol Blood Marrow Transplant. 2015 Sep;21(9):1583-8. doi: 10.1016/j.bbmt.2015.05.016. Epub 2015 May 22.

    PubMed 26009261

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Busulfan (conditioning for AUTO transplant), Etoposide (conditioning for AUTO transplant) and Cyclophosphamide (conditioning for AUTO transplant) in people with Diffuse, Large B-Cell, Lymphoma and Lymphoma, Low-Grade, run by Massachusetts General Hospital at 2 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 21 inclusion and 25 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 9 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 9 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?

Peripheral Blood All-cell Donor Chimerism (time frame: 100 days post allogeneic transplant). 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 NCT01181271, 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 9 Mar 2017.

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