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
  Purpose

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.


Condition Intervention Phase
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
Drug: Etoposide
Drug: Cyclophosphamide
Drug: Mesna
Drug: Phenytoin
Drug: Ursodiol
Other: Infusion of autologous peripheral blood stem cells
Drug: Neupogen
Drug: Fludarabine
Other: Peripheral blood stem cell transplant
Drug: Tacrolimus
Drug: Sirolimus
Drug: Methotrexate
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Sequential Myeloablative Autologous Stem Cell Transplantation Followed by Allogeneic Non-Myeloablative Stem Cell Transplantation for Patients With Poor Risk Lymphomas

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • 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.


Estimated Enrollment: 40
Study Start Date: August 2010
Estimated Study Completion Date: February 2015
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Autologous transplant
All patients will undergo autologous peripheral blood stem cell transplantation
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
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
Drug: Phenytoin
Phenytoin 200 mg BID orally given on days -8, -7, -6, -5, and -4 for seizure prophylaxis.
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01181271

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Massachusetts General Hospital
Dana-Farber Cancer Institute
Investigators
Principal Investigator: Yi-Bin A Chen, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Yi-Bin A. Chen, MD, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01181271     History of Changes
Other Study ID Numbers: DFCI Protocol No.: 10-057
Study First Received: August 12, 2010
Last Updated: April 7, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
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

Additional relevant MeSH terms:
Hodgkin Disease
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Large B-Cell, Diffuse
Lymphoma, T-Cell
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Lymphoma, B-Cell
Mesna
Phenytoin
Busulfan
Cyclophosphamide
Methotrexate
Fludarabine phosphate
Sirolimus
Everolimus
Tacrolimus
Etoposide phosphate
Fludarabine
Etoposide
Ursodeoxycholic Acid

ClinicalTrials.gov processed this record on August 28, 2014