Graft Versus Host Disease, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes
Conditions
Keywords
recurrent childhood acute lymphoblastic leukemia, recurrent adult Hodgkin lymphoma, Burkitt lymphoma, refractory multiple myeloma, stage I multiple myeloma, stage II multiple myeloma, stage III multiple myeloma, recurrent childhood lymphoblastic lymphoma, recurrent childhood acute myeloid leukemia, recurrent adult acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, relapsing chronic myelogenous leukemia, childhood diffuse large cell lymphoma, childhood immunoblastic large cell lymphoma, chronic phase chronic myelogenous leukemia, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, meningeal chronic myelogenous leukemia, adult acute myeloid leukemia in remission, adult acute lymphoblastic leukemia in remission, childhood acute myeloid leukemia in remission, childhood acute lymphoblastic leukemia in remission, recurrent/refractory childhood Hodgkin lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult Burkitt lymphoma, secondary acute myeloid leukemia, de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, graft versus host disease, recurrent childhood small noncleaved cell lymphoma, recurrent childhood large cell lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma, childhood myelodysplastic syndromes
Brief summary
RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Umbilical cord blood transplantation may allow doctors to give higher doses of chemotherapy or radiation therapy and kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of chemotherapy, radiation therapy, and umbilical cord blood transplantation in treating patients with hematologic cancer.
Detailed description
OBJECTIVES: I. Determine the safety, efficacy, and toxicity of using cord blood as a source for stem cell transplantation in patients with hematologic malignancies. OUTLINE: Patients undergo autologous bone marrow harvesting or peripheral stem cell collection prior to transplant regimen, unless the patient has acute leukemia in relapse, aplastic anemia, or myelodysplastic syndrome. Arm I: Patients eligible to undergo total body irradiation (TBI) first receive cyclophosphamide IV over 2 hours on days -5 and -4, then undergo TBI twice a day on days -3 to -1. Patients also receive antithymocyte globulin (ATG) IV over 10 hours on days -3 to -1. Cord blood is infused on day 0. Arm II: Patients not eligible to receive TBI receive oral busulfan every 6 hours on days -7 to -4 for a total of 16 doses. Cyclophosphamide, ATG, and cord blood are then administered as in arm I. All patients receive cyclosporine on days -2 to 180, methylprednisolone on days 5-180, and filgrastim (G-CSF) from day 1. Patients are followed weekly until day 180 and then monthly for 2 years. PROJECTED ACCRUAL: A total of 20 patients (10 patients per arm) will be accrued for this study within 4 years.
Interventions
BIOLOGICALanti-thymocyte globulin
IV
BIOLOGICALfilgrastim
IV
DRUGbusulfan
IV
DRUGcyclophosphamide
IV
DRUGcyclosporine
IV
DRUGmethylprednisolone
IV
PROCEDUREbone marrow ablation with stem cell support
IV
PROCEDUREumbilical cord blood transplantation
IV
RADIATIONradiation therapy
High energy X-rays
Sponsors
Roswell Park Cancer Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: Histologically proven hematologic malignancy Acute lymphocytic leukemia (ALL): In second or later remission In first remission with poor prognostic features (Philadelphia chromosome positive) Acute myeloid leukemia (AML): In second or later remission In first remission with poor prognostic features, e.g., Arising from myelodysplastic syndrome Cytogenetics with -5, -7, +8, 11q23 abnormalities Complex cytogenetics AML or ALL refractory to induction or in relapse Myelodysplastic syndrome Chronic myelogenous leukemia Severe aplastic anemia or Fanconi's anemia Relapsed Hodgkin's disease Relapsed non-Hodgkin's lymphoma Multiple myeloma No suitable family donor matched for 5 or 6 HLA antigens (A, B, DR) No suitable unrelated donor matched for 6 HLA antigens Cord blood donor available matched for 4-6 out of 6 HLA antigens PATIENT CHARACTERISTICS: Age: 5 to 50 Performance status: Karnofsky 70-100% Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin less than 3 times normal Alkaline phosphatase less than 3 times normal SGOT less than 3 times normal Renal: Creatinine less than 2 times normal OR Creatinine clearance greater than 60 mL/min Cardiovascular: MUGA with ejection fraction at least 50% Pulmonary: DLCO and spirometry at least 60% OR Exercise VO2 max/kg at least 15 mL/min/kg Other: HIV antibody negative Hepatitis B surface antigen negative No active bacterial, viral, or fungal infection PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: Not specified Endocrine therapy: Not specified Radiotherapy: Prior radiotherapy allowed If following limits have not been exceeded, patient may receive total body irradiation: No prior radiation to one entire kidney Whole liver received no greater than 1000 cGy No prior whole abdomen radiotherapy Small bowel received no greater than 3000 cGy Heart received no greater than 1800 cGy No prior whole lung radiotherapy CNS received less than 30 cGy (whole brain or any portion of the spine) Surgery: Not specified
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | day +100 after Cord Blood Transplant | Continuous complete remission (for patients in complete remission before treatment) or induced complete remission (for patients not in complete remission before treatment) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | 1 year | time to disease progression or death due to any cause |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 Eligible patients are treated with busulfan IV over 2 hours on days -7 to -4, cyclophosphamide IV over 2 hours on days -3 and -2, antithymocyte globulin (ATG) IV over 10 hours on days -3 to -1 (BuCyATG) and cord blood is infused on day 0; or are treated with cyclophosphamide IV over 2 hours on days -5 and -4, antithymocyte globulin (ATG) IV over 10 hours on days -3 to -1, and undergo TBI twice a day on days -3 to -1 (CyATGTBI) and cord blood is infused on day 0 | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Arm 1 |
|---|---|
| Age, Categorical <=18 years | 6 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 14 Participants |
| Age, Continuous | 32.5 years |
| Disease ALL | 3 Participants |
| Disease AML | 5 Participants |
| Disease Aplastic Anemia | 1 Participants |
| Disease CML | 7 Participants |
| Disease MDS/MPD | 4 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Region of Enrollment United States | 20 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 8 / 20 |
| other Total, other adverse events | 5 / 20 |
| serious Total, serious adverse events | 5 / 20 |
Outcome results
Primary
Overall Response Rate
Continuous complete remission (for patients in complete remission before treatment) or induced complete remission (for patients not in complete remission before treatment)
Time frame: day +100 after Cord Blood Transplant
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1 | Overall Response Rate | CR/CCR | 12 Participants |
| Arm 1 | Overall Response Rate | Progressed | 1 Participants |
| Arm 1 | Overall Response Rate | Not evaluable (early death) | 7 Participants |
Secondary
Progression-free Survival
time to disease progression or death due to any cause
Time frame: 1 year
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Progression-free Survival | 50 % of participants |