Clinical trial NCT01181271: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diffuse, Large B-Cell, Lymphoma
Lymphoma, Low-Grade
T-Cell Lymphoma
Mantle-Cell Lymphoma
Hodgkin's Lymphoma
Chronic Lymphocytic Leukemia
Lymphoma, Small Lymphocytic
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
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Dana-Farber Cancer Institute
First posted: 2010-08-13
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Peripheral Blood All-cell Donor Chimerism
timeFrame: 100 days post allogeneic transplant
Secondary outcomes:
measure: Number of Days After Allogeneic Transplant Until Absolute Neutrophil Count Was Equal to or Greater Than 500/uL
timeFrame: within 28 days after allogeneic transplant
measure: Cumulative Incidence of Grades II to IV Acute Graft Versus Host Disease (GVHD)
timeFrame: within 200 days after allogeneic transplant
measure: Cumulative Incidence of Extensive Chronic Graft-versus-host-disease
timeFrame: 1-year after allogeneic transplant
measure: Cumulative Incidence of Non-relapse Mortality
timeFrame: 2-years after allogeneic transplant
measure: Cumulative Incidence of Disease Relapse
timeFrame: 2-years after allogeneic transplant
measure: Estimated Two Year Progression Free Survival Rate for Participants Undergoing Both Autologous and Allogeneic Transplants
timeFrame: 2 years after allogeneic transplant
measure: Estimated Two Year Overall Survival Rate for Participants Undergoing Both Autologous and Allogeneic Transplants
timeFrame: Two-years after Allogeneic Transplant
measure: Estimated Two Year Progression Free Survival Rate for All Participants
timeFrame: 2 years
measure: Estimated Two Year Overall Survival Rate for All Participants
timeFrame: 2 years
measure: Estimated Two Year Progression Free Survival Rate for Participants Undergoing Only Autologous Transplant
timeFrame: Two Years
measure: Estimated Two Year Overall Survival Rate for Participants Undergoing Only Autologous Transplant
timeFrame: two years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Yi-Bin A Chen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.