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Tandem Auto-Allo Transplant for Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Dana-Farber Cancer Institute
Information provided by (Responsible Party):
Yi-Bin A. Chen, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01181271
First received: August 12, 2010
Last updated: April 7, 2014
Last verified: April 2014

August 12, 2010
April 7, 2014
August 2010
February 2014   (final data collection date for primary outcome measure)
Donor stem cell engraftment [ Time Frame: 60 days post allogeneic transplant ] [ Designated as safety issue: No ]
Assessment of donor stem cell engraftment such that ≥ 80% of hematopoietic elements are donor-derived as determined by chimerism assays from peripheral blood prior to day 60 after non-myeloablative allogeneic stem cell transplantation.
Same as current
Complete list of historical versions of study NCT01181271 on ClinicalTrials.gov Archive Site
Not Provided
Not Provided
Not Provided
Not Provided
 
Tandem Auto-Allo Transplant for Lymphoma
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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Diffuse, Large B-Cell, Lymphoma
  • Lymphoma, Low-Grade
  • T-Cell Lymphoma
  • Mantle-Cell Lymphoma
  • Hodgkin's Lymphoma
  • Chronic Lymphocytic Leukemia
  • Lymphoma, Small Lymphocytic
  • Drug: Busulfan
    0.8 mg/kg IV bolus 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
  • Drug: Etoposide
    Etoposide 30 mg/kg IV bolus QD on day -4. The total daily dose of etoposide will be 30 mg/kg.
  • Drug: Cyclophosphamide
    Cyclophosphamide 60 mg/kg IV bolus QD on days -3 and -2. The total daily dose of cyclophosphamide will be 60 mg/kg.
  • Drug: Mesna
    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 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
  • Drug: Phenytoin
    Phenytoin 200 mg BID orally given on days -8, -7, -6, -5, and -4 for seizure prophylaxis.
  • Drug: Ursodiol
    Ursodiol 300 mg TID orally given starting on day -8 and continuing daily until discharge for hepatic veno-occlusive disease (VOD) prophylaxis.
  • Other: Infusion of autologous peripheral blood stem cells
    Infusion of autologous peripheral blood stem cells on Day 0.
  • Drug: Neupogen
    Neupogen 5 mcg/kg SQ daily starting on day +1 until ANC is greater than or equal to 1000 per micro liter on two separate occasions or greater than 5000 per micro liter once
    Other Name: G-CSF
  • Drug: Fludarabine
    Fludarabine 30 mg/m2/d will be administered as a bolus infusion over approximately 30 minutes for 4 days on days -5, -4, -3, -2.
  • Drug: Busulfan
    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
  • Other: Peripheral blood stem cell transplant
    Donor 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
  • Drug: Tacrolimus
    Tacrolimus (FK506) will be given orally at a dose of 0.05 mg/kg PO BID starting day -3.
    Other Name: FK506
  • Drug: Sirolimus
    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
    Other Name: Rapamycin
  • Drug: Methotrexate
    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
  • Autologous transplant
    All patients will undergo autologous peripheral blood stem cell transplantation
    Interventions:
    • Drug: Busulfan
    • Drug: Etoposide
    • Drug: Cyclophosphamide
    • Drug: Mesna
    • Drug: Phenytoin
    • Drug: Ursodiol
    • Other: Infusion of autologous peripheral blood stem cells
    • Drug: Neupogen
  • Allogeneic stem cell transplantation
    Patients will be re-evaluated after autologous transplant prior to proceeding to non-myeloablative 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
    Interventions:
    • Drug: Phenytoin
    • Drug: Neupogen
    • Drug: Fludarabine
    • Drug: Busulfan
    • Other: Peripheral blood stem cell transplant
    • Drug: Tacrolimus
    • Drug: Sirolimus
    • Drug: Methotrexate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
40
February 2015
February 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 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
    • 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.

Exclusion Criteria:

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
  • 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.
Both
18 Years to 75 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01181271
DFCI Protocol No.: 10-057
Yes
Yi-Bin A. Chen, MD, Massachusetts General Hospital
Massachusetts General Hospital
Dana-Farber Cancer Institute
Principal Investigator: Yi-Bin A Chen, MD Massachusetts General Hospital
Massachusetts General Hospital
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP