Tandem Auto-Allo Transplant for Lymphoma

Mass General Brigham

Status and phase

Completed

Phase 2

Conditions

Diffuse, Large B-Cell, Lymphoma

T-Cell Lymphoma

Hodgkin's Lymphoma

Lymphoma, Low-Grade

Lymphoma, Small Lymphocytic

Chronic Lymphocytic Leukemia

Mantle-Cell Lymphoma

Treatments

Drug: Mesna (prior to AUTO transplant)

Drug: Fludarabine (conditioning for ALLO Transplant)

Drug: Etoposide (conditioning for AUTO transplant)

Drug: Methotrexate

Drug: Sirolimus

Drug: Tacrolimus

Drug: Cyclophosphamide (conditioning for AUTO transplant)

Other: non-myeloablative allogeneic (allo) transplant

Drug: Busulfan (conditioning for AUTO transplant)

Other: autologous (auto) peripheral blood stem cell transplantation

Drug: Busulfan (conditioning for ALLO Transplant)

Drug: Neupogen

Study type

Interventional

Funder types

Other

Identifiers

NCT01181271

10-057

Details and patient eligibility

About

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.

Full 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.

Enrollment

42 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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.

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

42 participants in 1 patient group

Autologous then Allogeneic transplant

Experimental group

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).

Treatment: