Leukemia, Lymphoma, Myelodysplastic Syndromes, Myeloproliferative Disorders
Conditions
Brief summary
RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill cancer cells. An umbilical cord blood transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving sirolimus and mycophenolate mofetil after the transplant may stop this from happening. PURPOSE: This phase II trial is studying how well giving fludarabine and cyclophosphamide together with total-body irradiation followed by an umbilical cord blood transplant, sirolimus, and mycophenolate mofetil works in treating patients with hematologic cancer.
Detailed description
OBJECTIVES: Primary * Determine the one- and two-year survival of patients with hematologic malignancies treated with a nonmyeloablative conditioning regimen comprising fludarabine, cyclophosphamide, and total-body irradiation followed by umbilical cord blood transplantation and post-transplant immunosuppression comprising sirolimus and mycophenolate mofetil. Secondary * Determine the six-month nonrelapse mortality of patients treated with this regimen. * Determine the presence of chimerism in patients treated with this regimen at days 21, 60, 100, 180, and 365. * Determine the incidence of neutrophil engraftment by day 42 in patients treated with this regimen. * Determine the incidence of platelet engraftment by six months in patients treated with this regimen. * Determine the incidence of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) at day 100 in patients treated with this regimen. * Determine the incidence of chronic GVHD at one year in patients treated with this regimen. * Determine the probability of overall survival within one or two years in patients treated with this regimen. * Determine the probability of progression-free survival within one or two years in patients treated with this regimen. * Determine the incidence of relapse or disease progression within one or two years in patients treated with this regimen. OUTLINE: This is a nonrandomized study. Patients are stratified into five disease groups: 1. acute myeloid leukemia, myelodysplastic syndromes, chronic myelogenous leukemia \[CML\] in first chronic phase and second chronic phase \[CP2\] after myeloid blast crisis; 2. acute lymphoblastic leukemia, Burkitt's lymphoma, CML CP2 post lymphoid blast crisis, 3. large-cell B and T-cell lymphoma, mantle cell lymphoma; 4. chronic lymphocytic leukemia/small lymphocytic lymphoma, prolymphocytic leukemia, marginal zone B-cell lymphoma, follicular lymphoma; 5. Hodgkin's lymphoma and multiple myeloma. * Nonmyeloablative conditioning: Patients receive fludarabine intravenously on days -6 to -2 and cyclophosphamide IV on day -6. Patients who did not undergo prior autologous transplant or who received ≤ 1 course of prior multiagent chemotherapy or no severely immunosuppressive therapy in the past 3 months also receive anti-thymocyte globulin IV on days -6 to -4. All patients also undergo total-body irradiation on day -1. * Umbilical cord blood transplant: Patients undergo umbilical cord blood transplantation on day 0. * Post-transplant immunosuppression: Sirolimus will be administered starting at day -3 with 8mg-12mg mg oral loading dose followed by single dose 4 mg/day with a target serum concentration of 3 to 12 mg/mL. Levels are to be monitored 3 times/week in the first 2 weeks, weekly until day +60, and as clinically indicated until day +100 post-transplantation. In the absence of acute GVHD sirolimus may be tapered starting at day +100 and eliminated by day +180 post-transplantation. Patients also receive mycophenolate mofetil IV on days -3 to 5 and then orally on days 6-30. After completion of study treatment, patients are followed periodically for 5 years. PROJECTED ACCRUAL: A total of 320 patients will be accrued for this study.
Interventions
BIOLOGICALanti-thymocyte globulin
Equine ATG dose is 15 mg/kg intravenously (IV) every 12 hours for 6 doses on days -6, - 5, and -4.
DRUGcyclophosphamide
Cyclophosphamide 50mg/kg x 1 to be administered IV over 2 hours with high volume fluid flush on day -6.
DRUGFludarabine
Fludarabine 40 mg/m2/day or 30 mg/m2/day intravenously (IV) as one hour infusion x 5 days, on day -6 to -2.
DRUGmycophenolate mofetil
Mycophenolate mofetil (MMF) 3 gram/day for patients who are ≥ 40 kg divided in 2 or 3 doses. Pediatric patient (\<40 kilograms) will receive MMF at the dose of 15 mg/kg/dose every 8 hours.
PROCEDUREumbilical cord blood transplantation
One or 2 UCB units may be infused to achieve the required cell dose.
RADIATIONtotal body irradiation
Administered Day -1, 200 cGy
DRUGSirolimus
Sirolimus will be administered starting at day -3 with 8mg-12mg mg oral loading dose followed by single dose 4 mg/day with a target serum concentration of 3 to 12 mg/mL. Levels are to be monitored 3 times/week in the first 2 weeks, weekly until day +60, and as clinically indicated until day +100 post-transplantation. In the absence of acute GVHD sirolimus may be tapered starting at day +100 and eliminated by day +180 post-transplantation.
Sponsors
Masonic Cancer Center, University of Minnesota
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 75 Years
Healthy volunteers
No
Inclusion criteria
Age, Graft Cell Dose and Graft HLA Criteria * Subjects must be \<70 years old. Subjects ages ≥ 70 and ≤ 75 may be eligible if they have a Co-Morbidity Scoring (HCT-CI) score ≤ 2. * The UCB graft is matched at 4-6 HLA-A, B, DRB1 antigens with the recipient. * Patients co-enrolled in MT-2006-01 Phase I Study of Infusion of Umbilical Cord Blood Derived CD25+CD4+ T-Regulatory (Treg) Cells after Non-Myeloablative Cord\\Blood Transplantation will receive grafts composed of 2 UCB units. Disease Criteria: * Acute Leukemias: * Acute myeloid leukemia: high risk complete remission 1 (CR1) (as evidenced by preceding myelodysplastic syndrome (MDS), high risk cytogenetics such as those associated with MDS or complex karyotype, \> 2 cycles to obtain CR or erythroblastic and megakaryocytic); second or greater CR. * Acute lymphoblastic leukemia/lymphoma: high risk CR1 as evidenced by high risk cytogenetics (e.g. t(9;22), t(1;19),t(4;11), other myeloid/lymphoid or mixed lineage leukemia \[MLL\] rearrangements, hypodiploidy or Ikaros family zinc finger 1 \[IKZF1\]), \> 1 cycle to obtain CR or evidence of minimal residual disease (MRD). Patients in second or greater CR are also eligible. * Burkitt's lymphoma in CR2 or subsequent CR * Natural Killer cell malignancies * Chronic myelogenous leukemia: all types except refractory blast crisis. Chronic phase patients must have failed or been intolerant to Gleevec * Myelodysplastic syndrome: * Large-cell lymphoma, Hodgkin lymphoma and multiple myeloma with chemotherapy sensitive disease that has failed or patients who are ineligible for an autologous transplant. * Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone B-cell lymphoma, follicular lymphoma, which have progressed within 12 months of achieving a partial or complete remission. Patients who had remissions lasting \> 12 months, are eligible after at least two prior therapies. Patients with bulky disease should be considered for debulking chemotherapy before transplant. Patients with refractory disease are eligible, unless has bulky disease and an estimated tumor doubling time of less than one month. * Lymphoplasmacytic lymphoma, mantle-cell lymphoma, prolymphocytic leukemia are eligible after initial therapy if chemotherapy sensitive. * Refractory leukemia or MDS. * Bone marrow failure syndromes, except for Fanconi Anemia * Myeloproliferative syndromes Patients who have undergone an autologous transplant \>12 months prior to allogeneic transplantation Adequate Organ Function and Performance Status
Exclusion criteria
* \< 70 years with an available 5-6/6 HLA-A, B, DRB1 matched sibling donor * Pregnancy or breastfeeding * Evidence of human immunodeficiency virus (HIV) infection or known HIV positive serology * Current active serious infection * Unless in post-chemotherapy and radioimmunoconjugated antibody induced aplasia, when he/she would be eligible for Arm 3, patients with acute leukemia in morphologic relapse/ persistent disease defined as \> 5% blasts in normocellular bone marrow OR any % blasts if blasts have unique morphologic markers (e.g. Auer rods) or associated cytogenetic markers that allows morphologic relapse to be distinguished are not eligible. * Chronic myelogenous leukemia (CML) in refractory blast crisis * Large cell lymphoma, mantle cell lymphoma and Hodgkin disease that is progressive on salvage therapy. Stable disease is acceptable to move forward provided it is non-bulky. * Active central nervous system malignancy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Were Alive at 1 Year Post Transplant | 1 Year | Overall Survival - Number of patients alive at 1 year post transplant |
| Number of Participants Who Were Alive at 2 Years Post Transplant | 2 Years | Overall Survival - Number of patients alive at 2 years post transplant |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Donor Chimerism at 100 Days | 100 days | Chimerism studies will be performed on the blood and bone marrow (BM). BM chimerism days 21 and 100, at 6 months and 1 year to determine the relative contribution of donor and recipient hematopoiesis. |
| Percentage of Donor Chimerism at 180 Days | 180 Days | Chimerism studies will be performed on the blood and bone marrow (BM). BM chimerism days 21 and 100, at 6 months and 1 year to determine the relative contribution of donor and recipient hematopoiesis. |
| Percentage of Donor Chimerism at 365 Days | 365 days | Chimerism studies will be performed on the blood and bone marrow (BM). BM chimerism days 21 and 100, at 6 months and 1 year to determine the relative contribution of donor and recipient hematopoiesis. |
| Number of Participants With Neutrophil Engraftment | Day 42 | Time to 1st 3 consecutive days with absolute neutrophil count (ANC) \> 5 x 10\^8/L and percentage of patients with neutrophil recovery by day 42 (Cumulative incidence). |
| Number of Participants With Platelet Engraftment | Day 180 | Time to platelets \> 20,000 (first of 3 consecutive days) with no platelet transfusions for seven days and percentage of patients with platelet engraftment \>50,000 by day 100. |
| Number of Participants Who Were Dead at 6 Months After Study Completion | Month 6 | Incidence of Non-relapse mortality - Number of Patients Dead at 6 Months after study completion |
| Number of Participants With Chronic Graft-Versus-Host Disease | 1 Year | Determine the incidence of chronic GVHD at 1 year after transplant. Patients will be staged weekly between days 0 and 100 after transplantation using standard criteria. Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level. |
| Number of Participants Experiencing Progression-free Survival | 1 Year | Incidence of Progression-free survival - Number of patients who were alive and did not have disease progression. Patients with leukemia and lymphoma involving the bone marrow (BM) and multiple myeloma will have this done by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients with lymphoma and myeloma will have radiology studies such as plain X-rays or CT scans and/or other studies such as blood tumor markers to document presence or absence of disease as clinically indicated. |
| Number of Participants Experiencing Progression-free Survival at 2 Years | 2 Years | Incidence of Progression-free survival - Number of patients who were alive and did not have disease progression |
| Number of Participants Experiencing Relapse (Incidence of Relapse) | Year 1 | Patients with leukemia and lymphoma involving the BM and multiple myeloma will have this done by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients with lymphoma and myeloma will have radiology studies such as plain X-rays or CT scans and/or other studies such as blood tumor markers to document presence or absence of disease as clinically indicated. |
| Number of Participants Experiencing Relapse (Incidence of Relapse) at 2 Years | 2 years | Patients with leukemia and lymphoma involving the BM and multiple myeloma will have this done by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients with lymphoma and myeloma will have radiology studies such as plain X-rays or CT scans and/or other studies such as blood tumor markers to document presence or absence of disease as clinically indicated. |
| Number of Participants With Acute Graft-versus-host Disease (GVHD) | Day 100 | Determine the incidence of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) at day 100 post transplant. Patients will be staged weekly between days 0 and 100 after transplantation using standard criteria used for staging. Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level. |
| Percentage of Donor Chimerism at 21 Days | 21 days | Chimerism studies will be performed on the blood and bone marrow (BM). BM chimerism days 21 and 100, at 6 months and 1 year to determine the relative contribution of donor and recipient hematopoiesis. |
Countries
United States
Participant flow
Recruitment details
7 patients were excluded from receiving the treatment as they were not eligible. 4 patients were removed from the study because the participating site withdrew the participation from the study
Participants by arm
| Arm | Count |
|---|---|
| Arm 1-Previous Autologous Transplant hematologic malignancy patients who have received a previous autologous transplant or ≥ 2 cycle of multiagent chemotherapy within the last 3 months previous to umbilical cord blood transplant (UCBT). Conditioning Fludarabine dose of 40 mg/m2/day x 5, cyclophosphamide and total body irradiation without anti-thymocyte globulin followed by umbilical cord blood transplantation, and peri-transplant Mycophenolate Mofetil and Sirolimus. | 98 |
| Arm 2 - No Prior Autologous Transplant Arm 2 - hematologic malignancy patients who have not been treated with prior autologous transplant or ≤ 1 cycle of chemotherapy in the 3 months previous to umbilical cord blood transplant (UCBT), and who should receive anti-thymocyte globulin as conditioning regimen. Conditioning Fludarabine dose of 40 mg/m2/day x 5, cyclophosphamide and total body irradiation with anti-thymocyte globulin followed by umbilical cord blood transplantation, and peri-transplant Mycophenolate Mofetil and Sirolimus. | 71 |
| Arm 3 - Refractory Leukemia/Lymphoma Arm 3 - patients with refractory leukemia or lymphoma who have been rendered aplastic either by induction chemotherapy or radioimmunoconjugated monoclonal antibody therapy. Conditioning Fludarabine dose of 40 mg/m2/day x 5, cyclophosphamide and total body irradiation with anti-thymocyte globulin followed by umbilical cord blood transplantation, and peri-transplant Mycophenolate Mofetil and Sirolimus. | 7 |
| Arm 4: MT2006-01 Coenrolling Patients Arm 4 - hematologic malignancy patients enrolled in MT2006-01. Conditioning Fludarabine dose of 40 mg/m2/day x 5, cyclophosphamide and total body irradiation with or without anti-thymocyte globulin followed by umbilical cord blood transplantation, and peri-transplant Mycophenolate Mofetil and Sirolimus. | 34 |
| Arm 5 - Previous Autologous Transplant Arm 5 - hematologic malignancy patients who have received a previous autologous transplant or ≥ 2 cycle of multiagent chemotherapy within the last 3 months previous to umbilical cord blood transplant (UCBT). Conditioning Fludarabine dose of 30 mg/m2/day x 5, cyclophosphamide and total body irradiation without anti-thymocyte globulin followed by umbilical cord blood transplantation, and peri-transplant Mycophenolate Mofetil and Sirolimus. | 39 |
| Arm 6 - No Prior Autologous Transplant Arm 6 - hematologic malignancy patients who have not been treated with prior autologous transplant or ≤ 1 cycle of chemotherapy in the 3 months previous to umbilical cord blood transplant (UCBT), and who should receive anti-thymocyte globulin as conditioning regimen. Conditioning Fludarabine dose of 30 mg/m2/day x 5, cyclophosphamide and total body irradiation with anti-thymocyte globulin followed by umbilical cord blood transplantation, and peri-transplant Mycophenolate Mofetil and Sirolimus. | 35 |
| Total | 284 |
Baseline characteristics
| Characteristic | Arm 1-Previous Autologous Transplant | Arm 2 - No Prior Autologous Transplant | Arm 3 - Refractory Leukemia/Lymphoma | Arm 4: MT2006-01 Coenrolling Patients | Arm 5 - Previous Autologous Transplant | Arm 6 - No Prior Autologous Transplant | Total |
|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 7 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 11 Participants |
| Age, Categorical >=65 years | 12 Participants | 13 Participants | 1 Participants | 4 Participants | 10 Participants | 15 Participants | 55 Participants |
| Age, Categorical Between 18 and 65 years | 79 Participants | 55 Participants | 6 Participants | 30 Participants | 29 Participants | 19 Participants | 218 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 1 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 9 Participants | 4 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 15 Participants |
| Race (NIH/OMB) White | 82 Participants | 61 Participants | 5 Participants | 31 Participants | 39 Participants | 30 Participants | 248 Participants |
| Region of Enrollment United States | 98 participants | 71 participants | 7 participants | 34 participants | 39 participants | 35 participants | 284 participants |
| Sex: Female, Male Female | 37 Participants | 29 Participants | 5 Participants | 16 Participants | 14 Participants | 15 Participants | 116 Participants |
| Sex: Female, Male Male | 61 Participants | 42 Participants | 2 Participants | 18 Participants | 25 Participants | 20 Participants | 168 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 48 / 98 | 40 / 71 | 6 / 7 | 14 / 34 | 18 / 39 | 12 / 35 |
| other Total, other adverse events | 76 / 98 | 54 / 71 | 5 / 7 | 20 / 34 | 33 / 39 | 35 / 35 |
| serious Total, serious adverse events | 53 / 98 | 48 / 71 | 3 / 7 | 11 / 34 | 2 / 39 | 4 / 35 |
Outcome results
Primary
Number of Participants Who Were Alive at 1 Year Post Transplant
Overall Survival - Number of patients alive at 1 year post transplant
Time frame: 1 Year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1-Previous Autologous Transplant | Number of Participants Who Were Alive at 1 Year Post Transplant | 59 Participants |
| Arm 2 - No Prior Autologous Transplant | Number of Participants Who Were Alive at 1 Year Post Transplant | 40 Participants |
| Arm 3 - Refractory Leukemia/Lymphoma | Number of Participants Who Were Alive at 1 Year Post Transplant | 1 Participants |
| Arm 4: MT2006-01 Coenrolling Patients | Number of Participants Who Were Alive at 1 Year Post Transplant | 26 Participants |
| Arm 5 - Previous Autologous Transplant | Number of Participants Who Were Alive at 1 Year Post Transplant | 26 Participants |
| Arm 6 - No Prior Autologous Transplant | Number of Participants Who Were Alive at 1 Year Post Transplant | 25 Participants |
Primary
Number of Participants Who Were Alive at 2 Years Post Transplant
Overall Survival - Number of patients alive at 2 years post transplant
Time frame: 2 Years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1-Previous Autologous Transplant | Number of Participants Who Were Alive at 2 Years Post Transplant | 50 Participants |
| Arm 2 - No Prior Autologous Transplant | Number of Participants Who Were Alive at 2 Years Post Transplant | 31 Participants |
| Arm 3 - Refractory Leukemia/Lymphoma | Number of Participants Who Were Alive at 2 Years Post Transplant | 1 Participants |
| Arm 4: MT2006-01 Coenrolling Patients | Number of Participants Who Were Alive at 2 Years Post Transplant | 20 Participants |
| Arm 5 - Previous Autologous Transplant | Number of Participants Who Were Alive at 2 Years Post Transplant | 21 Participants |
| Arm 6 - No Prior Autologous Transplant | Number of Participants Who Were Alive at 2 Years Post Transplant | 23 Participants |
Secondary
Number of Participants Experiencing Progression-free Survival
Incidence of Progression-free survival - Number of patients who were alive and did not have disease progression. Patients with leukemia and lymphoma involving the bone marrow (BM) and multiple myeloma will have this done by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients with lymphoma and myeloma will have radiology studies such as plain X-rays or CT scans and/or other studies such as blood tumor markers to document presence or absence of disease as clinically indicated.
Time frame: 1 Year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1-Previous Autologous Transplant | Number of Participants Experiencing Progression-free Survival | 43 Participants |
| Arm 2 - No Prior Autologous Transplant | Number of Participants Experiencing Progression-free Survival | 32 Participants |
| Arm 3 - Refractory Leukemia/Lymphoma | Number of Participants Experiencing Progression-free Survival | 1 Participants |
| Arm 4: MT2006-01 Coenrolling Patients | Number of Participants Experiencing Progression-free Survival | 21 Participants |
| Arm 5 - Previous Autologous Transplant | Number of Participants Experiencing Progression-free Survival | 16 Participants |
| Arm 6 - No Prior Autologous Transplant | Number of Participants Experiencing Progression-free Survival | 24 Participants |
Secondary
Number of Participants Experiencing Progression-free Survival at 2 Years
Incidence of Progression-free survival - Number of patients who were alive and did not have disease progression
Time frame: 2 Years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1-Previous Autologous Transplant | Number of Participants Experiencing Progression-free Survival at 2 Years | 36 Participants |
| Arm 2 - No Prior Autologous Transplant | Number of Participants Experiencing Progression-free Survival at 2 Years | 25 Participants |
| Arm 3 - Refractory Leukemia/Lymphoma | Number of Participants Experiencing Progression-free Survival at 2 Years | 1 Participants |
| Arm 4: MT2006-01 Coenrolling Patients | Number of Participants Experiencing Progression-free Survival at 2 Years | 17 Participants |
| Arm 5 - Previous Autologous Transplant | Number of Participants Experiencing Progression-free Survival at 2 Years | 16 Participants |
| Arm 6 - No Prior Autologous Transplant | Number of Participants Experiencing Progression-free Survival at 2 Years | 20 Participants |
Secondary
Number of Participants Experiencing Relapse (Incidence of Relapse)
Patients with leukemia and lymphoma involving the BM and multiple myeloma will have this done by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients with lymphoma and myeloma will have radiology studies such as plain X-rays or CT scans and/or other studies such as blood tumor markers to document presence or absence of disease as clinically indicated.
Time frame: Year 1
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1-Previous Autologous Transplant | Number of Participants Experiencing Relapse (Incidence of Relapse) | 43 Participants |
| Arm 2 - No Prior Autologous Transplant | Number of Participants Experiencing Relapse (Incidence of Relapse) | 14 Participants |
| Arm 3 - Refractory Leukemia/Lymphoma | Number of Participants Experiencing Relapse (Incidence of Relapse) | 4 Participants |
| Arm 4: MT2006-01 Coenrolling Patients | Number of Participants Experiencing Relapse (Incidence of Relapse) | 7 Participants |
| Arm 5 - Previous Autologous Transplant | Number of Participants Experiencing Relapse (Incidence of Relapse) | 20 Participants |
| Arm 6 - No Prior Autologous Transplant | Number of Participants Experiencing Relapse (Incidence of Relapse) | 2 Participants |
Secondary
Number of Participants Experiencing Relapse (Incidence of Relapse) at 2 Years
Patients with leukemia and lymphoma involving the BM and multiple myeloma will have this done by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients with lymphoma and myeloma will have radiology studies such as plain X-rays or CT scans and/or other studies such as blood tumor markers to document presence or absence of disease as clinically indicated.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1-Previous Autologous Transplant | Number of Participants Experiencing Relapse (Incidence of Relapse) at 2 Years | 49 Participants |
| Arm 2 - No Prior Autologous Transplant | Number of Participants Experiencing Relapse (Incidence of Relapse) at 2 Years | 19 Participants |
| Arm 3 - Refractory Leukemia/Lymphoma | Number of Participants Experiencing Relapse (Incidence of Relapse) at 2 Years | 4 Participants |
| Arm 4: MT2006-01 Coenrolling Patients | Number of Participants Experiencing Relapse (Incidence of Relapse) at 2 Years | 11 Participants |
| Arm 5 - Previous Autologous Transplant | Number of Participants Experiencing Relapse (Incidence of Relapse) at 2 Years | 20 Participants |
| Arm 6 - No Prior Autologous Transplant | Number of Participants Experiencing Relapse (Incidence of Relapse) at 2 Years | 4 Participants |
Secondary
Number of Participants Who Were Dead at 6 Months After Study Completion
Incidence of Non-relapse mortality - Number of Patients Dead at 6 Months after study completion
Time frame: Month 6
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1-Previous Autologous Transplant | Number of Participants Who Were Dead at 6 Months After Study Completion | 10 Participants |
| Arm 2 - No Prior Autologous Transplant | Number of Participants Who Were Dead at 6 Months After Study Completion | 20 Participants |
| Arm 3 - Refractory Leukemia/Lymphoma | Number of Participants Who Were Dead at 6 Months After Study Completion | 2 Participants |
| Arm 4: MT2006-01 Coenrolling Patients | Number of Participants Who Were Dead at 6 Months After Study Completion | 5 Participants |
| Arm 5 - Previous Autologous Transplant | Number of Participants Who Were Dead at 6 Months After Study Completion | 3 Participants |
| Arm 6 - No Prior Autologous Transplant | Number of Participants Who Were Dead at 6 Months After Study Completion | 6 Participants |
Secondary
Number of Participants With Acute Graft-versus-host Disease (GVHD)
Determine the incidence of grade II-IV and grade III-IV acute graft-versus-host disease (GVHD) at day 100 post transplant. Patients will be staged weekly between days 0 and 100 after transplantation using standard criteria used for staging. Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level.
Time frame: Day 100
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1-Previous Autologous Transplant | Number of Participants With Acute Graft-versus-host Disease (GVHD) | 45 Participants |
| Arm 2 - No Prior Autologous Transplant | Number of Participants With Acute Graft-versus-host Disease (GVHD) | 24 Participants |
| Arm 3 - Refractory Leukemia/Lymphoma | Number of Participants With Acute Graft-versus-host Disease (GVHD) | 1 Participants |
| Arm 4: MT2006-01 Coenrolling Patients | Number of Participants With Acute Graft-versus-host Disease (GVHD) | 12 Participants |
| Arm 5 - Previous Autologous Transplant | Number of Participants With Acute Graft-versus-host Disease (GVHD) | 13 Participants |
| Arm 6 - No Prior Autologous Transplant | Number of Participants With Acute Graft-versus-host Disease (GVHD) | 13 Participants |
Secondary
Number of Participants With Chronic Graft-Versus-Host Disease
Determine the incidence of chronic GVHD at 1 year after transplant. Patients will be staged weekly between days 0 and 100 after transplantation using standard criteria. Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level.
Time frame: 1 Year
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1-Previous Autologous Transplant | Number of Participants With Chronic Graft-Versus-Host Disease | 18 Participants |
| Arm 2 - No Prior Autologous Transplant | Number of Participants With Chronic Graft-Versus-Host Disease | 20 Participants |
| Arm 3 - Refractory Leukemia/Lymphoma | Number of Participants With Chronic Graft-Versus-Host Disease | 0 Participants |
| Arm 4: MT2006-01 Coenrolling Patients | Number of Participants With Chronic Graft-Versus-Host Disease | 3 Participants |
| Arm 5 - Previous Autologous Transplant | Number of Participants With Chronic Graft-Versus-Host Disease | 3 Participants |
| Arm 6 - No Prior Autologous Transplant | Number of Participants With Chronic Graft-Versus-Host Disease | 3 Participants |
Secondary
Number of Participants With Neutrophil Engraftment
Time to 1st 3 consecutive days with absolute neutrophil count (ANC) \> 5 x 10\^8/L and percentage of patients with neutrophil recovery by day 42 (Cumulative incidence).
Time frame: Day 42
Population: 7 participants were not evaluable
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1-Previous Autologous Transplant | Number of Participants With Neutrophil Engraftment | 93 Participants |
| Arm 2 - No Prior Autologous Transplant | Number of Participants With Neutrophil Engraftment | 65 Participants |
| Arm 3 - Refractory Leukemia/Lymphoma | Number of Participants With Neutrophil Engraftment | 6 Participants |
| Arm 4: MT2006-01 Coenrolling Patients | Number of Participants With Neutrophil Engraftment | 32 Participants |
| Arm 5 - Previous Autologous Transplant | Number of Participants With Neutrophil Engraftment | 32 Participants |
| Arm 6 - No Prior Autologous Transplant | Number of Participants With Neutrophil Engraftment | 29 Participants |
Secondary
Number of Participants With Platelet Engraftment
Time to platelets \> 20,000 (first of 3 consecutive days) with no platelet transfusions for seven days and percentage of patients with platelet engraftment \>50,000 by day 100.
Time frame: Day 180
Population: 13 participants were not evaluable
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm 1-Previous Autologous Transplant | Number of Participants With Platelet Engraftment | 75 Participants |
| Arm 2 - No Prior Autologous Transplant | Number of Participants With Platelet Engraftment | 47 Participants |
| Arm 3 - Refractory Leukemia/Lymphoma | Number of Participants With Platelet Engraftment | 3 Participants |
| Arm 4: MT2006-01 Coenrolling Patients | Number of Participants With Platelet Engraftment | 28 Participants |
| Arm 5 - Previous Autologous Transplant | Number of Participants With Platelet Engraftment | 34 Participants |
| Arm 6 - No Prior Autologous Transplant | Number of Participants With Platelet Engraftment | 25 Participants |
Secondary
Percentage of Donor Chimerism at 100 Days
Chimerism studies will be performed on the blood and bone marrow (BM). BM chimerism days 21 and 100, at 6 months and 1 year to determine the relative contribution of donor and recipient hematopoiesis.
Time frame: 100 days
Population: A total of 85 participants were not evaluable.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1-Previous Autologous Transplant | Percentage of Donor Chimerism at 100 Days | 94 percentage of donor cells | Standard Deviation 18 |
| Arm 2 - No Prior Autologous Transplant | Percentage of Donor Chimerism at 100 Days | 94 percentage of donor cells | Standard Deviation 21 |
| Arm 3 - Refractory Leukemia/Lymphoma | Percentage of Donor Chimerism at 100 Days | 100 percentage of donor cells | Standard Deviation 0 |
| Arm 4: MT2006-01 Coenrolling Patients | Percentage of Donor Chimerism at 100 Days | 93 percentage of donor cells | Standard Deviation 23 |
| Arm 5 - Previous Autologous Transplant | Percentage of Donor Chimerism at 100 Days | 85 percentage of donor cells | Standard Deviation 31 |
| Arm 6 - No Prior Autologous Transplant | Percentage of Donor Chimerism at 100 Days | 86 percentage of donor cells | Standard Deviation 32 |
Secondary
Percentage of Donor Chimerism at 180 Days
Chimerism studies will be performed on the blood and bone marrow (BM). BM chimerism days 21 and 100, at 6 months and 1 year to determine the relative contribution of donor and recipient hematopoiesis.
Time frame: 180 Days
Population: A total of 134 participants were not evaluable
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1-Previous Autologous Transplant | Percentage of Donor Chimerism at 180 Days | 96 percentage of donor cells | Standard Deviation 18 |
| Arm 2 - No Prior Autologous Transplant | Percentage of Donor Chimerism at 180 Days | 98 percentage of donor cells | Standard Deviation 6 |
| Arm 3 - Refractory Leukemia/Lymphoma | Percentage of Donor Chimerism at 180 Days | 88 percentage of donor cells | Standard Deviation 17 |
| Arm 4: MT2006-01 Coenrolling Patients | Percentage of Donor Chimerism at 180 Days | 94 percentage of donor cells | Standard Deviation 16 |
| Arm 5 - Previous Autologous Transplant | Percentage of Donor Chimerism at 180 Days | 91 percentage of donor cells | Standard Deviation 26 |
| Arm 6 - No Prior Autologous Transplant | Percentage of Donor Chimerism at 180 Days | 98 percentage of donor cells | Standard Deviation 10 |
Secondary
Percentage of Donor Chimerism at 21 Days
Chimerism studies will be performed on the blood and bone marrow (BM). BM chimerism days 21 and 100, at 6 months and 1 year to determine the relative contribution of donor and recipient hematopoiesis.
Time frame: 21 days
Population: A total of 43 participants were not evaluable
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1-Previous Autologous Transplant | Percentage of Donor Chimerism at 21 Days | 77 percentage of donor cells | Standard Deviation 25 |
| Arm 2 - No Prior Autologous Transplant | Percentage of Donor Chimerism at 21 Days | 73 percentage of donor cells | Standard Deviation 32 |
| Arm 3 - Refractory Leukemia/Lymphoma | Percentage of Donor Chimerism at 21 Days | 57 percentage of donor cells | Standard Deviation 29 |
| Arm 4: MT2006-01 Coenrolling Patients | Percentage of Donor Chimerism at 21 Days | 77 percentage of donor cells | Standard Deviation 21 |
| Arm 5 - Previous Autologous Transplant | Percentage of Donor Chimerism at 21 Days | 69 percentage of donor cells | Standard Deviation 32 |
| Arm 6 - No Prior Autologous Transplant | Percentage of Donor Chimerism at 21 Days | 68 percentage of donor cells | Standard Deviation 33 |
Secondary
Percentage of Donor Chimerism at 365 Days
Chimerism studies will be performed on the blood and bone marrow (BM). BM chimerism days 21 and 100, at 6 months and 1 year to determine the relative contribution of donor and recipient hematopoiesis.
Time frame: 365 days
Population: A total of 160 participants were not evaluable
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1-Previous Autologous Transplant | Percentage of Donor Chimerism at 365 Days | 99 percentage of donor cells | Standard Deviation 2 |
| Arm 2 - No Prior Autologous Transplant | Percentage of Donor Chimerism at 365 Days | 98 percentage of donor cells | Standard Deviation 12 |
| Arm 4: MT2006-01 Coenrolling Patients | Percentage of Donor Chimerism at 365 Days | 99 percentage of donor cells | Standard Deviation 6 |
| Arm 5 - Previous Autologous Transplant | Percentage of Donor Chimerism at 365 Days | 87 percentage of donor cells | Standard Deviation 34 |
| Arm 6 - No Prior Autologous Transplant | Percentage of Donor Chimerism at 365 Days | 100 percentage of donor cells | Standard Deviation 0 |