Trial Outcomes & Findings for Tandem Auto-Allo Transplant for Lymphoma (NCT NCT01181271)

NCT ID: NCT01181271

Last Updated: 2017-03-09

Results Overview

Successful donor stem cell engraftment is defined as when ≥ 80% of hematopoietic elements are donor-derived as determined by chimerism assays from peripheral blood at day 100 after non-myeloablative allogeneic stem cell transplantation.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 42 participants
• Primary outcome timeframe: 100 days post allogeneic transplant
• Results posted on: 2017-03-09

Participant Flow

Participants were enrolled between October 2010 and June 2013.

Participant milestones

Measure	Autologous Then Allogeneic Transplant Autologous, then Allogeneic Stem Cell Transplantation
Autologous Transplant STARTED	42
Autologous Transplant COMPLETED	42
Autologous Transplant NOT COMPLETED	0
Evaluation for Allogeneic Transplant STARTED	42
Evaluation for Allogeneic Transplant COMPLETED	29
Evaluation for Allogeneic Transplant NOT COMPLETED	13
Allogeneic Transplant STARTED	29
Allogeneic Transplant COMPLETED	29
Allogeneic Transplant NOT COMPLETED	0

Reasons for withdrawal

Measure	Autologous Then Allogeneic Transplant Autologous, then Allogeneic Stem Cell Transplantation
Evaluation for Allogeneic Transplant Lack of Efficacy	6
Evaluation for Allogeneic Transplant Withdrawal by Subject	4
Evaluation for Allogeneic Transplant No suitable donor	2
Evaluation for Allogeneic Transplant therapy-related AML diagnosed	1

Baseline Characteristics

Tandem Auto-Allo Transplant for Lymphoma

Baseline characteristics by cohort

Measure	Autologous Then Allogeneic Transplant n=42 Participants Autologous then allogeneic stem cell transplantation
Age, Continuous	56.5 years n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants
Region of Enrollment United States	42 Participants n=5 Participants
Prior lines of chemotherapy	2 lines n=5 Participants
Diagnosis Relapsed/refractory Diffuse Large B-cell Lymphoma	10 Participants n=5 Participants
Diagnosis Relapsed/refractory Non-Hodgkin Lymphoma	6 Participants n=5 Participants
Diagnosis Double-Expressing Non-Hodgkin Lymphoma	9 Participants n=5 Participants
Diagnosis Transformed B-cell Non-Hodgkin Lymphoma	8 Participants n=5 Participants
Diagnosis T-cell Non-Hodgkin Lymphoma	4 Participants n=5 Participants
Diagnosis Mantle cell Non-Hodgkin Lymphoma	3 Participants n=5 Participants
Diagnosis Relapsed/Refractory Hodgkin Lymphoma	1 Participants n=5 Participants
Diagnosis Heavy chain disease	1 Participants n=5 Participants
Disease status at study entry Partial Response	21 Participants n=5 Participants
Disease status at study entry Complete Response	21 Participants n=5 Participants

PRIMARY outcome

Timeframe: 100 days post allogeneic transplant

Population: Participants who underwent the full tandem AUTO-ALLO stem cell transplant

Successful donor stem cell engraftment is defined as when ≥ 80% of hematopoietic elements are donor-derived as determined by chimerism assays from peripheral blood at day 100 after non-myeloablative allogeneic stem cell transplantation.

Outcome measures

Measure

Autologous Then Allogeneic Transplant n=29 Participants 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).

Peripheral Blood All-cell Donor Chimerism

95 percentage of donor-derived elements Interval 83.0 to 99.0

SECONDARY outcome

Timeframe: within 28 days after allogeneic transplant

Population: This was only measured in the 17 participants who experienced a hematological nadir after allo transplant.

Outcome measures

Measure

Autologous Then Allogeneic Transplant n=17 Participants 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).

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

12 days Interval 1.0 to 18.0

SECONDARY outcome

Timeframe: within 200 days after allogeneic transplant

Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.

Outcome measures

Measure

Autologous Then Allogeneic Transplant n=29 Participants 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).

Cumulative Incidence of Grades II to IV Acute Graft Versus Host Disease (GVHD)

13.8 percentage of participants Interval 5.3 to 26.3

SECONDARY outcome

Timeframe: 1-year after allogeneic transplant

Extensive chronic graft versus-host-disease (GVHD) was defined as GVHD that required systemic immunosuppression.

Outcome measures

Measure

Autologous Then Allogeneic Transplant n=29 Participants 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).

Cumulative Incidence of Extensive Chronic Graft-versus-host-disease

37.9 percentage of participants Interval 23.1 to 52.7

SECONDARY outcome

Timeframe: 2-years after allogeneic transplant

Non-relapse mortality is defined as participants who die from causes other than their underlying disease relapse, such as infection or graft versus host disease

Outcome measures

Measure

Autologous Then Allogeneic Transplant n=29 Participants 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).

Cumulative Incidence of Non-relapse Mortality

11.1 percentage of participants Interval 3.5 to 23.6

SECONDARY outcome

Timeframe: 2-years after allogeneic transplant

Outcome measures

Measure

Autologous Then Allogeneic Transplant n=29 Participants 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).

Cumulative Incidence of Disease Relapse

17.2 percentage of participants Interval 7.5 to 30.4

SECONDARY outcome

Timeframe: 2 years after allogeneic transplant

Outcome measures

Measure

Autologous Then Allogeneic Transplant n=29 Participants 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).

Estimated Two Year Progression Free Survival Rate for Participants Undergoing Both Autologous and Allogeneic Transplants

72 percentage of participants Interval 55.0 to 83.0

SECONDARY outcome

Timeframe: Two-years after Allogeneic Transplant

Outcome measures

Measure

Autologous Then Allogeneic Transplant n=29 Participants 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).

Estimated Two Year Overall Survival Rate for Participants Undergoing Both Autologous and Allogeneic Transplants

89 percentage of participants Interval 74.0 to 96.0

SECONDARY outcome

Timeframe: 2 years

Outcome measures

Measure

Autologous Then Allogeneic Transplant n=42 Participants 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).

Estimated Two Year Progression Free Survival Rate for All Participants

64 percentage of participants Interval 50.0 to 75.0

SECONDARY outcome

Timeframe: 2 years

Outcome measures

Measure

Autologous Then Allogeneic Transplant n=42 Participants 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).

Estimated Two Year Overall Survival Rate for All Participants

83 percentage of participants Interval 70.0 to 90.0

SECONDARY outcome

Timeframe: Two Years

Population: Participants who ONLY underwent Autologous transplant (did not proceed to Allogeneic)

Outcome measures

Measure

Autologous Then Allogeneic Transplant n=13 Participants 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).

Estimated Two Year Progression Free Survival Rate for Participants Undergoing Only Autologous Transplant

46 percentage of participants Interval 23.0 to 66.0

SECONDARY outcome

Timeframe: two years

Population: Participants who ONLY underwent Autologous transplant, did not proceed to Allogeneic transplant

Outcome measures

Measure

Autologous Then Allogeneic Transplant n=13 Participants 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).

Estimated Two Year Overall Survival Rate for Participants Undergoing Only Autologous Transplant

69 percentage of participants Interval 43.0 to 85.0

Adverse Events

Autologous Then Allogeneic Transplant

Serious events: 5 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Measure	Autologous Then Allogeneic Transplant n=42 participants at risk 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).
Respiratory, thoracic and mediastinal disorders respiratory failure	2.4% 1/42 • Until 30 months after allogeneic transplant.
Infections and infestations sepsis	2.4% 1/42 • Until 30 months after allogeneic transplant.
Respiratory, thoracic and mediastinal disorders Adult Respiratory Distress Syndrome	2.4% 1/42 • Until 30 months after allogeneic transplant.
Cardiac disorders Atrioventricular block	2.4% 1/42 • Until 30 months after allogeneic transplant.
General disorders Death, not otherwise specified	2.4% 1/42 • Until 30 months after allogeneic transplant.

Other adverse events

Measure	Autologous Then Allogeneic Transplant n=42 participants at risk 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).
Blood and lymphatic system disorders anemia	9.5% 4/42 • Until 30 months after allogeneic transplant.
Blood and lymphatic system disorders febrile neutropenia	11.9% 5/42 • Until 30 months after allogeneic transplant.
Gastrointestinal disorders colitis	4.8% 2/42 • Until 30 months after allogeneic transplant.
Gastrointestinal disorders diarrhea	9.5% 4/42 • Until 30 months after allogeneic transplant.
Gastrointestinal disorders mucositis oral	9.5% 4/42 • Until 30 months after allogeneic transplant.
Gastrointestinal disorders nausea	7.1% 3/42 • Until 30 months after allogeneic transplant.
General disorders edema	4.8% 2/42 • Until 30 months after allogeneic transplant.
Investigations neutrophil count decreased	4.8% 2/42 • Until 30 months after allogeneic transplant.
Investigations platelet count decreased	14.3% 6/42 • Until 30 months after allogeneic transplant.
Investigations weight loss	4.8% 2/42 • Until 30 months after allogeneic transplant.
Musculoskeletal and connective tissue disorders muscle weakness	7.1% 3/42 • Until 30 months after allogeneic transplant.
Respiratory, thoracic and mediastinal disorders dyspnea	9.5% 4/42 • Until 30 months after allogeneic transplant.

Additional Information

Yi-Bin Chen, MD

Mass General Hospital

Phone: 617-726-5765

Email: ychen6@partners.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place