Tandem Auto-Allo Transplant for Lymphoma

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Brief Title

Tandem Auto-Allo Transplant for Lymphoma

Official Title

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

Brief 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. 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.
    

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.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Peripheral Blood All-cell Donor Chimerism

Secondary Outcome

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

Condition

Diffuse, Large B-Cell, Lymphoma

Intervention

Busulfan (conditioning for AUTO transplant)

Study Arms / Comparison Groups

 Autologous then Allogeneic transplant
Description:  All 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).

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

42

Start Date

August 2010

Completion Date

February 2016

Primary Completion Date

February 2014

Eligibility 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.
      

Gender

All

Ages

18 Years - 75 Years

Accepts Healthy Volunteers

No

Contacts

Yi-Bin A Chen, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01181271

Organization ID

10-057


Responsible Party

Principal Investigator

Study Sponsor

Massachusetts General Hospital

Collaborators

 Dana-Farber Cancer Institute

Study Sponsor

Yi-Bin A Chen, MD, Principal Investigator, Massachusetts General Hospital


Verification Date

January 2017