Chemotherapy, Radiation Therapy, and Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer

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Primary Purpose

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

anti-thymocyte globulin

filgrastim

busulfan

cyclophosphamide

cyclosporine

methylprednisolone

bone marrow ablation with stem cell support

umbilical cord blood transplantation

radiation therapy

About this trial

This is an interventional treatment trial for Graft Versus Host Disease focused on measuring 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

Eligibility Criteria

5 Years - 50 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Roswell Park Cancer Institute

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm 1

Arm Description

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

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

Progression-free Survival

time to disease progression or death due to any cause

Full Information

NCT ID

NCT00003270

First Posted

November 1, 1999

Last Updated

November 25, 2019

Sponsor

Roswell Park Cancer Institute

1. Study Identification

Unique Protocol Identification Number

NCT00003270

Brief Title

Chemotherapy, Radiation Therapy, and Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer

Official Title

Cord Blood Transplantation for Hematologic Malignancies and Bone Marrow Failure Syndromes

Study Type

Interventional

2. Study Status

Record Verification Date

November 2019

Overall Recruitment Status

Completed

Study Start Date

September 4, 1997 (Actual)

Primary Completion Date

October 16, 2017 (Actual)

Study Completion Date

October 16, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Roswell Park Cancer Institute

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Graft Versus Host Disease, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm 1

Arm Type

Experimental

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

anti-thymocyte globulin

Intervention Description

IV

Intervention Type

Biological

Intervention Name(s)

filgrastim

Intervention Description

IV

Intervention Type

Drug

Intervention Name(s)

busulfan

Intervention Description

IV

Intervention Type

Drug

Intervention Name(s)

cyclophosphamide

Intervention Description

IV

Intervention Type

Drug

Intervention Name(s)

cyclosporine

Intervention Description

IV

Intervention Type

Drug

Intervention Name(s)

methylprednisolone

Intervention Description

IV

Intervention Type

Procedure

Intervention Name(s)

bone marrow ablation with stem cell support

Intervention Description

IV

Intervention Type

Procedure

Intervention Name(s)

umbilical cord blood transplantation

Intervention Description

IV

Intervention Type

Radiation

Intervention Name(s)

radiation therapy

Intervention Description

High energy X-rays

Primary Outcome Measure Information:

Title

Overall Response Rate

Description

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

Secondary Outcome Measure Information:

Title

Progression-free Survival

Description

time to disease progression or death due to any cause

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

5 Years

Maximum Age & Unit of Time

50 Years

Accepts Healthy Volunteers

No

Eligibility 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Barbara Jean Bambach, MD

Organizational Affiliation

Roswell Park Cancer Institute

Official's Role

Study Chair

Facility Information:

Facility Name

Roswell Park Cancer Institute

City

Buffalo

State/Province

New York

ZIP/Postal Code

14263-0001

Country

United States

Graft Versus Host Disease, Leukemia, Lymphoma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial