Chemotherapy, Radiation Therapy, and Umbilical Cord Blood Transplantation in Treating Patients With Hematologic Cancer
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Arm 1 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 |
Biological: anti-thymocyte globulin
IV
Biological: filgrastim
IV
Drug: busulfan
IV
Drug: cyclophosphamide
IV
Drug: cyclosporine
IV
Drug: methylprednisolone
IV
Procedure: bone marrow ablation with stem cell support
IV
Procedure: umbilical cord blood transplantation
IV
Radiation: radiation therapy
High energy X-rays
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- Progression-free Survival [1 year]
time to disease progression or death due to any cause
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Roswell Park Cancer Institute | Buffalo | New York | United States | 14263-0001 |
Sponsors and Collaborators
- Roswell Park Cancer Institute
Investigators
- Study Chair: Barbara Jean Bambach, MD, Roswell Park Cancer Institute
Study Documents (Full-Text)
More Information
Publications
None provided.- DS 97-26
- DS 97-26
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Arm 1 |
|---|---|
| Arm/Group Description | 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 |
| Period Title: Overall Study | |
| STARTED | 20 |
| COMPLETED | 20 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Arm 1 |
|---|---|
| Arm/Group Description | 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 |
| Overall Participants | 20 |
| Age (Count of Participants) | |
| <=18 years |
6
30%
|
| Between 18 and 65 years |
14
70%
|
| >=65 years |
0
0%
|
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
32.5
|
| Sex: Female, Male (Count of Participants) | |
| Female |
10
50%
|
| Male |
10
50%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |
| Hispanic or Latino |
2
10%
|
| Not Hispanic or Latino |
18
90%
|
| Unknown or Not Reported |
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
0
0%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
2
10%
|
| White |
18
90%
|
| More than one race |
0
0%
|
| Unknown or Not Reported |
0
0%
|
| Region of Enrollment (participants) [Number] | |
| United States |
20
100%
|
| Disease (Count of Participants) | |
| ALL |
3
15%
|
| AML |
5
25%
|
| Aplastic Anemia |
1
5%
|
| CML |
7
35%
|
| MDS/MPD |
4
20%
|
Outcome Measures
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Arm 1 |
|---|---|
| Arm/Group Description | 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 |
| Measure Participants | 20 |
| CR/CCR |
12
60%
|
| Progressed |
1
5%
|
| Not evaluable (early death) |
7
35%
|
| Title | Progression-free Survival |
|---|---|
| Description | time to disease progression or death due to any cause |
| Time Frame | 1 year |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Arm 1 |
|---|---|
| Arm/Group Description | 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 |
| Measure Participants | 20 |
| Number (95% Confidence Interval) [% of participants] |
50
250%
|
Adverse Events
| Time Frame | Adverse Event, Serious Adverse Event and All Cause Mortality are from start of treatment (Day -7 or -5) through day +100 after cord blood infusion | |
|---|---|---|
| Adverse Event Reporting Description | SAE is delayed engraftment or failed to engraft Died before engraftment is defined as death before Absolute Neutrophil Count recovery Failure to engraft is defined as survival until at least day +42 without Absolute Neutrophil Count recovery Other AEs include acute GVHD grade III-IV and RRT grade 3-4 RRT is defined using Bearman Regimen Related Toxicity Criteria Acute GVHD grade III-IV is defined using Glucksberg criteria | |
| Arm/Group Title | Arm 1 | |
| Arm/Group Description | 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 | |
All Cause Mortality |
||
| Arm 1 | ||
| Affected / at Risk (%) | # Events | |
| Total | 8/20 (40%) | |
Serious Adverse Events |
||
| Arm 1 | ||
| Affected / at Risk (%) | # Events | |
| Total | 5/20 (25%) | |
| Blood and lymphatic system disorders | ||
| DBE/FTE | 5/20 (25%) | 5 |
Other (Not Including Serious) Adverse Events |
||
| Arm 1 | ||
| Affected / at Risk (%) | # Events | |
| Total | 5/20 (25%) | |
| Immune system disorders | ||
| Severe Acute graft-versus-host disease | 5/20 (25%) | 5 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Theresa Hahn |
|---|---|
| Organization | Roswell Park Comprehensive Cancer Center |
| Phone | 716-845-5819 |
| theresa.hahn@roswellpark.org |
- DS 97-26
- DS 97-26