High-Dose Chemotherapy With or Without Total-Body Irradiation Followed by Autologous Stem Cell Transplant in Treating Patients With Hematologic Cancer or Solid Tumors
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Purpose
RATIONALE: Giving high-dose chemotherapy with or without total-body irradiation before an autologous stem cell transplant stops the growth of cancer cells by stopping them from dividing or by killing them. It is also given to prepare the patient's bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy.
PURPOSE: This phase II/III clinical trial is studying different high-dose chemotherapy regimens with or without total-body irradiation to compare how well they work when given before autologous stem cell transplant in treating patients with hematologic cancer or solid tumors.
| Condition | Intervention | Phase |
|---|---|---|
|
Brain and Central Nervous System Tumors Childhood Germ Cell Tumor Leukemia Lymphoma Multiple Myeloma and Plasma Cell Neoplasm Neuroblastoma Unspecified Adult Solid Tumor, Protocol Specific |
Drug: busulfan Drug: carboplatin Drug: carmustine Drug: cyclophosphamide Drug: etoposide Drug: melphalan Drug: thiotepa Radiation: total-body irradiation |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Autologous Blood and Marrow Transplantation for Hematologic Malignancies and Selected Solid Tumors |
- Progression-free survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- Efficacy [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- Toxicity [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
- Response rates [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: 10 years ] [ Designated as safety issue: No ]
- Impact of prognostic significance of disease-specific standard-, intermediate-, and high-risk groups on prediction of relapse risk post-transplantation [ Time Frame: 5 years ] [ Designated as safety issue: No ]
| Enrollment: | 174 |
| Study Start Date: | June 2006 |
| Estimated Primary Completion Date: | June 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: CT6
Patients receive cyclophosphamide IV over 2 hours on days -5 and -4 and undergo total-body irradiation twice daily on days -3 to -1. Patients undergo ASCT on day 0.
|
Drug: cyclophosphamide
Given IV
Radiation: total-body irradiation
Given on 2 days
|
|
Experimental: BuC2iv
Patients receive busulfan IV over 2 hours every 6 hours on days -7 to -4 for a total of 16 doses and cyclophosphamide IV over 2 hours on days -3 and -2.
|
Drug: busulfan
Given IV
Drug: cyclophosphamide
Given IV
|
|
Experimental: CBV
Patients receive etoposide IV continuously over 34 hours beginning on day -8, cyclophosphamide IV over 2 hours on days -7 to -4, and carmustine IV over 2 hours on day -3.
|
Drug: carmustine
Given IV
Drug: cyclophosphamide
Given IV
Drug: etoposide
Given IV
|
|
Experimental: M200
Patients receive 200 mg/m² of melphalan IV over 30 minutes on day -2.
|
Drug: melphalan
Given IV
|
|
Experimental: M120
Patients receive 120 mg/m² of melphalan IV over 30 minutes on day -2.
|
Drug: melphalan
Given IV
|
|
Experimental: VCp
Patients receive etoposide IV over 2-3 hours and carboplatin IV over 30 minutes on days -6 to -4. Approximately 4-8 weeks after the first stem cell transplant, patients receive etoposide IV over 2-3 hours and carboplatin IV over 30 minutes on days -6 to -4.
|
Drug: carboplatin
Given IV
Drug: etoposide
Given IV
|
|
Experimental: TtC1500/ECpM
Patients receive thiotepa IV over 2 hours on days -7 to -5 and cyclophosphamide IV over 1-2 hours on days -5 to -2. Approximately 4-8 weeks after the first stem cell transplant, patients receive etoposide IV continuously and carboplatin IV continuously on days -7 to -4 and melphalan IV over 30 minutes on days -7 to -5.
|
Drug: carboplatin
Given IV
Drug: cyclophosphamide
Given IV
Drug: etoposide
Given IV
Drug: melphalan
Given IV
Drug: thiotepa
Given IV
|
|
Experimental: CTtCp
Patients receive cyclophosphamide IV continuously, carboplatin IV continuously, and thiotepa IV continuously on days -7 to -4.
|
Drug: carmustine
Given IV
Drug: cyclophosphamide
Given IV
Drug: thiotepa
Given IV
|
Show Detailed Description
Eligibility| Ages Eligible for Study: | 4 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
Histologically confirmed diagnosis of 1 of the following:
Hodgkin lymphoma, meeting the following criteria:
- Relapsed or refractory disease after ≥ 1 prior standard chemotherapy regimen
- Must have received 2 prior courses of salvage chemotherapy followed by disease-specific restaging prior to mobilization and collection of stem cells
Non-Hodgkin lymphoma, meeting the following criteria:
Low-, intermediate-, or high-grade disease, meeting 1 of the following criteria:
- Relapsed or refractory disease after ≥ 1 prior standard chemotherapy regimen
- Small non-cleaved cell or lymphoblastic lymphoma in first complete remission (CR) at high risk for relapse by IPI score
- Must have received 2 prior courses of salvage chemotherapy followed by disease-specific restaging prior to mobilization and collection of stem cells
Acute myeloid leukemia, meeting the following criteria:
- Low- or high-risk disease in first or second CR or greater
- Must have received 2 prior courses of chemotherapy (induction chemotherapy and mobilization chemotherapy) followed by disease-specific restaging prior to mobilization and collection of stem cells
- Risk of allogeneic stem cell transplantation outweighs the benefits
Acute lymphoblastic leukemia, meeting the following criteria:
- Low- or high-risk disease in first or second CR or greater
- Must have received 2 prior courses of chemotherapy (induction chemotherapy and mobilization chemotherapy) followed by disease-specific restaging prior to mobilization and collection of stem cells
- Risk of allogeneic stem cell transplantation outweighs the benefits
Multiple myeloma, meeting the following criteria:
- Low- or high-risk disease in first or greater response (stable disease or better) OR responding disease and now in first progression
- Must have received 2 prior courses of chemotherapy (≥ 1 of the courses must have been standard induction therapy) followed by disease-specific restaging prior to mobilization and collection of stem cells
Other malignant lymphoproliferative disease, including chronic lymphocytic leukemia or Waldenstrom macroglobulinemia, meeting the following criterion:
- Relapsed or refractory disease after first-line chemotherapy
Amyloidosis, meeting the following criteria:
- Primary or previously treated disease
- Prior induction chemotherapy is not required
- Patients with malignancies who would be treated with an autologous stem cell transplant but have a syngeneic donor. A syngeneic donor would be considered to have the same risk as an autologous stem cell transplant patient.
Solid tumors, including any of the following:
Testicular cancer, meeting the following criteria:
Relapsed disease or primary progressive disease that responded to salvage therapy
- Must have received 2 prior courses of salvage chemotherapy followed by disease-specific restaging prior to mobilization and collection of stem cells
- Neuroblastoma, meeting the following criteria:
= 30 years of age or under
Relapsed disease OR newly diagnosed advanced disease
Must have received 2 prior courses of chemotherapy (induction chemotherapy and mobilization chemotherapy) followed by disease-specific restaging prior to mobilization and collection of stem cells
- Small round blue cell tumor, meeting the following criteria:
= 30 years of age or under
- Relapsed disease OR newly diagnosed advanced disease
Must have received either prior standard chemotherapy or surgical intervention
- Other solid tumor, meeting the following criteria:
- Recurrent disease following conventional therapy OR at high risk for relapse
- Must have received 2 prior courses of chemotherapy followed by disease-specific restaging prior to mobilization and collection of stem cells
Demonstrates chemosensitivity
- Allogeneic stem cell transplantation (SCT) is not possible, or is not desirable (e.g., over 65 years of age; no compatible donor available; and estimated risk of graft-versus-host disease complications are greater than risk of recurrence after autologous SCT)
Adequate bone marrow or peripheral blood stem cell dose obtained
- Total CD34+ peripheral blood stem cell dose ≥ 2 x 10^6/kg, or if unable to collect this dose, total nucleated cell bone marrow dose ≥ 1 x 10^8/kg
- Bone marrow may be used in conjunction with blood progenitor cells NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma. However, this protocol uses the former terminology.
PATIENT CHARACTERISTICS:
Karnofsky performance status (PS) 70-100% or PS 0-2
- Patients with amyloidosis or multiple myeloma with decreased Karnofsky PS due to disease are eligible
- Life expectancy > 2 months
- ANC > 1,500/mm³
- Platelet count > 75,000/mm³
- Bilirubin < 3 times upper limit of normal (ULN)
- Alkaline phosphatase < 3 times ULN
- SGOT < 3 times ULN
Creatinine clearance ≥ 50 mL/min (requirement waived in selected multiple myeloma and amyloidosis patients due to renal compromise characteristic of the disease)
- Glomerular filtration rate by renal scan required for patients with neuroblastoma
- HIV I and HIV II antibody negative
- DLCO or DLVA ≥ 50% of predicted (DLCO to be corrected for hemoglobin and/or alveolar ventilation)
- Cardiac ventricular ejection fraction ≥ 50% by radionuclide ventriculogram or echocardiogram
No uncontrolled or severe cardiovascular disease, including any of the following:
- Myocardial infarction within the past 6 months
- Congestive heart failure
- Symptomatic angina
- Life-threatening arrhythmia
- Hypertension
No active bacterial, viral, or fungal infection
- Patients with positive CMV IgM and/or positive hepatitis serologies demonstrating infection, or any other active infection, will require an Infectious Disease consult and subsequent clearance
- No active peptic ulcer disease
- No uncontrolled diabetes mellitus
- No other serious organ dysfunction unless it is caused by the underlying disease
- No serious medical or psychiatric illness
- No psychiatric condition that would prevent delivery of care (psychology clearance is necessary)
- Not pregnant
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No radiotherapy within 3 weeks prior to stem cell harvest
Contacts and Locations| United States, New York | |
| Roswell Park Cancer Institute | |
| Buffalo, New York, United States, 14263-0001 | |
| Principal Investigator: | Philip L. McCarthy, MD | Roswell Park Cancer Institute |
More Information
Additional Information:
No publications provided
| Responsible Party: | Roswell Park Cancer Institute |
| ClinicalTrials.gov Identifier: | NCT00536601 History of Changes |
| Other Study ID Numbers: | CDR0000565267, RPCI-I-72806 |
| Study First Received: | September 27, 2007 |
| Last Updated: | September 18, 2012 |
| Health Authority: | United States: Institutional Review Board United States: Food and Drug Administration |
Keywords provided by Roswell Park Cancer Institute:
|
unspecified adult solid tumor, protocol specific unspecified childhood solid tumor, protocol specific adult acute lymphoblastic leukemia in remission adult acute myeloid leukemia in remission childhood acute lymphoblastic leukemia in remission childhood acute myeloid leukemia in remission childhood malignant testicular germ cell tumor recurrent malignant testicular germ cell tumor disseminated neuroblastoma localized unresectable neuroblastoma recurrent neuroblastoma regional neuroblastoma stage 4S neuroblastoma stage I multiple myeloma stage II multiple myeloma |
stage III multiple myeloma refractory multiple myeloma primary systemic amyloidosis recurrent adult Hodgkin lymphoma recurrent/refractory childhood Hodgkin lymphoma recurrent childhood grade III lymphomatoid granulomatosis recurrent childhood large cell lymphoma recurrent childhood lymphoblastic lymphoma recurrent childhood small noncleaved cell lymphoma stage I childhood lymphoblastic lymphoma stage II childhood lymphoblastic lymphoma stage III childhood lymphoblastic lymphoma stage IV childhood lymphoblastic lymphoma stage I childhood small noncleaved cell lymphoma stage II childhood small noncleaved cell lymphoma |
Additional relevant MeSH terms:
|
Neoplasms Leukemia Lymphoma Multiple Myeloma Neoplasms, Plasma Cell Plasmacytoma Nervous System Neoplasms Neuroblastoma Lymphoma, Large-Cell, Immunoblastic Lymphoma, Non-Hodgkin Central Nervous System Neoplasms Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Lymphoproliferative Disorders Lymphatic Diseases |
Immunoproliferative Disorders Immune System Diseases Hemostatic Disorders Vascular Diseases Cardiovascular Diseases Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Neoplasms by Site Nervous System Diseases Neuroectodermal Tumors, Primitive, Peripheral Neuroectodermal Tumors, Primitive Neoplasms, Neuroepithelial Neuroectodermal Tumors |
ClinicalTrials.gov processed this record on May 16, 2013