Clinical trial NCT01118013
Conditions: Leukemia Lymphoma Lymphoproliferative Disorder Multiple Myeloma and Plasma Cell Neoplasm Myelodysplastic Syndromes Myelodysplastic/Myeloproliferative Neoplasms
Keywords: adult acute myeloid leukemia with 11q23 (MLL) abnormalities adult acute myeloid leukemia with inv(16)(p13;q22) adult acute myeloid leukemia with t(15;17)(q22;q12) adult acute myeloid leukemia with t(16;16)(p13;q22) adult acute myeloid leukemia with t(8;21)(q22;q22) juvenile myelomonocytic leukemia prolymphocytic leukemia recurrent adult acute myeloid leukemia recurrent adult T-cell leukemia/lymphoma recurrent childhood acute myeloid leukemia refractory chronic lymphocytic leukemia recurrent adult Hodgkin lymphoma recurrent adult Burkitt lymphoma recurrent adult diffuse large cell lymphoma recurrent adult diffuse mixed cell lymphoma recurrent adult diffuse small cleaved cell lymphoma recurrent adult grade III lymphomatoid granulomatosis recurrent adult immunoblastic large cell lymphoma recurrent adult lymphoblastic lymphoma recurrent childhood grade III lymphomatoid granulomatosis recurrent childhood large cell lymphoma recurrent childhood lymphoblastic lymphoma recurrent childhood small noncleaved cell lymphoma recurrent cutaneous T-cell non-Hodgkin lymphoma recurrent mycosis fungoides/Sezary syndrome recurrent grade 1 follicular lymphoma recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma recurrent mantle cell lymphoma recurrent marginal zone lymphoma recurrent small lymphocytic lymphoma recurrent/refractory childhood Hodgkin lymphoma childhood diffuse large cell lymphoma childhood grade III lymphomatoid granulomatosis childhood immunoblastic large cell lymphoma childhood nasal type extranodal NK/T-cell lymphoma post-transplant lymphoproliferative disorder stage I multiple myeloma stage II multiple myeloma stage III multiple myeloma refractory multiple myeloma de novo myelodysplastic syndromes previously treated myelodysplastic syndromes secondary myelodysplastic syndromes childhood myelodysplastic syndromes recurrent childhood anaplastic large cell lymphoma adult acute myelomonocytic leukemia (M4) childhood acute myelomonocytic leukemia (M4) adult acute minimally differentiated myeloid leukemia (M0) childhood acute minimally differentiated myeloid leukemia (M0) adult acute myeloblastic leukemia without maturation (M1) childhood acute myeloblastic leukemia without maturation (M1) adult acute myeloblastic leukemia with maturation (M2) childhood acute myeloblastic leukemia with maturation (M2) adult acute promyelocytic leukemia (M3) childhood acute promyelocytic leukemia (M3) adult acute monoblastic leukemia (M5a) adult acute monocytic leukemia (M5b) childhood acute monoblastic leukemia (M5a) childhood acute monocytic leukemia (M5b) adult erythroleukemia (M6a) adult pure erythroid leukemia (M6b) childhood acute erythroleukemia (M6) adult acute megakaryoblastic leukemia (M7) childhood acute megakaryocytic leukemia (M7) childhood Burkitt lymphoma atypical chronic myeloid leukemia, BCR-ABL1 negative chronic myelomonocytic leukemia cutaneous B-cell non-Hodgkin lymphoma extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue nodal marginal zone B-cell lymphoma splenic marginal zone lymphoma myelodysplastic/myeloproliferative neoplasm, unclassifiable
Sponsor: Alliance for Clinical Trials in Oncology
Start date: 2010-12-01; Completion date: 2013-08-01
Enrollment: 6 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
RATIONALE: Giving chemotherapy, such as busulfan and fludarabine phosphate, before a peripheral blood stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving methotrexate, tacrolimus, and antithymocyte globulin before and after the transplant may stop this from happening. Once the donated stem cells begin working, the patient's immune system may see the remaining cancer cells as not belonging in the patient's body and destroy them (called graft-versus-tumor effect). Giving an infusion of the donor's white blood cells (donor lymphocyte infusion) may boost this effect.

PURPOSE: This phase II trial is studying how well donor stem cell transplant works in treating patients with relapsed hematologic malignancies or secondary myelodysplasia previously treated with high-dose chemotherapy and autologous stem cell transplant .

Detailed description:
OBJECTIVES:

Primary

* To demonstrate the efficacy of performing reduced-intensity conditioning allogeneic hematopoietic cell transplantation in patients with relapsed hematologic malignancies or secondary myelodysplasia after completion of prior high-dose chemotherapy and autologous hematopoietic stem cell transplantation.
* To compare the strategy of this regimen with the strategy used in CALGB-100002.

Secondary

* To describe the response rate at 6 and 12 months in patients treated with this regimen.
* To describe the time-to-progression in patients treated with this regimen.
* To determine the ability to use pharmacokinetic-directed busulfan to achieve AUC within 20% of target AUC in \> 80% of patients.
* To determine percent of donor chimerism in T-cell, myeloid and B-cell populations achieved with this regimen compared with CALGB-100002.
* To determine the risk of acute and chronic graft-versus-host disease and other toxicities of this regimen in these patients.
* To describe the overall survival and disease-free survival of patients treated on this regimen.
* To determine the rate of viral, bacterial, and fungal opportunistic infections occurring in the first year after transplantation compared with CALGB-100002.

OUTLINE: This is a multicenter study.

* Preparative Regimen:

  * Busulfan test dose: Patients receive busulfan IV over 45 minutes once during days -14 and -9.
  * Busulfan treatment dose: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -3 and busulfan IV over 3 hours on days -6 to -3.
* Graft-vs-Host Disease (GVHD) Prophylaxis:

  * HLA-identical donor: Patients receive antithymocyte globulin IV over 6-10 hours on days -6 to -5; oral tacrolimus twice daily on days -2 to 90 followed by a taper\* as tolerated until day 150 or 180; and methotrexate IV on days 1, 3, and 6.

NOTE: \* Tacrolimus may be tapered on days 60-90 if donor chimerism of CD3+ cells is \< 50% at day 60 or patient has progressive disease.

* Matched-unrelated donor: Patients receive antithymocyte globulin, tacrolimus, and methotrexate as in HLA-identical donor regimen. Patients also receive oral mycophenolate mofetil twice daily on days 0 to 60.

  * Allogeneic Stem Cell Transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation on days 0 and 1. Patients then receive filgrastim subcutaneously daily beginning on day 7 and continuing until blood counts recover.
  * Donor Lymphocyte Infusion (DLI): After day 180 (or day 210 for patients without an HLA-identical donor), patients with stable or progressive disease and no active GVHD may receive up to 3 DLIs every 8 weeks.

Blood samples are collected at baseline and then periodically during study therapy for pharmacokinetic studies.

After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for up to 5½ years.

Arms: arm 1: Matched-unrelated donor: Patients receive antithymocyte globulin, tacrolimus, and methotrexate as in HLA-identical donor regimen. Patients also receive oral mycophenolate mofetil twice daily on days 0 to 60.

Allogeneic Stem Cell Transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation on days 0 and 1. Patients then receive filgrastim subcutaneously daily beginning on day 7 and continuing until blood counts recover.

Donor Lymphocyte Infusion (DLI): After day 180 (or day 210 for patients without an HLA-identical donor), patients with stable or progressive disease and no active GVHD may receive up to 3 DLIs every 8 weeks.

Blood samples are collected at baseline and then periodically during study therapy for pharmacokinetic studies.

After completion of study therapy, patients are followed up every 3 months for 2 years and then every 6 months for up to 5½ years.
Interventions: intervention 1: anti-thymocyte globulin intervention 2: donor lymphocytes intervention 3: filgrastim intervention 4: therapeutic allogeneic lymphocytes intervention 5: busulfan intervention 6: fludarabine phosphate intervention 7: methotrexate intervention 8: mycophenolate mofetil intervention 9: tacrolimus intervention 10: reduced-intensity transplant conditioning procedure intervention 11: allogeneic hematopoietic stem cell transplantation intervention 12: peripheral blood stem cell transplantation
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None intervention 5: None intervention 6: None intervention 7: None intervention 8: None intervention 9: None intervention 10: None intervention 11: None intervention 12: None

Protocol documents: