Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information

Alternate Title

High-Dose Chemotherapy With or Without Total-Body Irradiation Followed by Autologous Stem Cell Transplant in Treating Patients With Hematologic Cancer or Solid Tumors

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase III, Phase II	Treatment	Active	4 and over	NCI	RPCI-I-72806 I 72806, NCT00536601

Objectives

Primary

1. Compare the progression-free survival (PFS) of patients with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) treated with different disease-specific high-dose conditioning regimens followed by autologous stem cell transplantation.
2. Compare the PFS of patients with high-risk vs standard-risk HL, NHL, or multiple myeloma, in terms of disease progression or relapse after transplant.
3. Determine if known prognostic factors (when available) can be used to group patients with acute lymphocytic leukemia or acute myeloid leukemia into high risk and standard risk groups.

Secondary

1. Compare the toxicity of the different disease-specific high-dose conditioning regimens in these patients.
2. Compare the overall survival of patients treated with these regimens.

Entry Criteria

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
  • 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 10⁶/kg, or if unable to collect this dose, total nucleated cell bone marrow dose ≥ 1 x 10⁸/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.]

Prior/Concurrent Therapy:

• See Disease Characteristics
• No radiotherapy within 3 weeks prior to stem cell harvest

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

Expected Enrollment

Outcomes

Progression-free survival
Efficacy
Toxicity
Response rates
Overall survival
Impact of prognostic significance of disease-specific standard-, intermediate-, and high-risk groups on prediction of relapse risk post-transplantation

Outline

Patients are retrospectively stratified according to risk for recurrence (low [standard]-risk vs high-risk). Patients are assigned to a conditioning regimen based on disease, age, and co-morbidities.

• Acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL): Patients receive 1 of the following conditioning regimens followed by autologous stem cell transplant (ASCT):
  • 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.
  
  
  
  • 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. Patients undergo ASCT on day 0.
  
  
  



• Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL): Patients receive 1 of the following conditioning regimens followed by ASCT:
  • 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. Patients undergo ASCT on day 0.
  
  
  
  • 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. Patients undergo ASCT on day 0.
  
  
  



• Multiple myeloma (MM) or amyloidosis: Patients receive 1 of the following conditioning regimens followed by ASCT:
  • M200: Patients receive 200 mg/m² of melphalan IV over 30 minutes on day -2. Patients undergo ASCT on day 0.
  
  
  
  • M120: Patients receive 120 mg/m² of melphalan IV over 30 minutes on day -2. Patients undergo ASCT on day 0.
  
  
  



• Testicular cancer: Patients receive the following conditioning regimen followed by tandem ASCT:
  • VCp: Patients receive etoposide IV over 2-3 hours and carboplatin IV over 30 minutes on days -6 to -4. Patients undergo ASCT on day 0. Approximately 4-8 weeks after the first transplant, patients receive etoposide IV over 2-3 hours and carboplatin IV over 30 minutes on days -6 to -4. Patients undergo a second ASCT on day 0.



• Neuroblastoma or small round blue cell tumor: Patients receive the following conditioning regimen followed by tandem ASCT:
  • 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. Patients undergo ASCT on day 0. Approximately 4-8 weeks after the first 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. Patients undergo a second ASCT on day 0.



• Other solid tumors: Patients receive the following conditioning regimen followed by ASCT:
  • CTtCp: Patients receive cyclophosphamide IV continuously, carboplatin IV continuously, and thiotepa IV continuously on days -7 to -4. Patients undergo ASCT on day 0.

Trial Contact Information

Trial Lead Organizations

Roswell Park Cancer Institute

Philip McCarthy, MD, Principal investigator		Ph: 716-845-4074; 800-685-6825 Email: philip.mccarthy@roswellpark.org

U.S.A.
New York
	Buffalo
	Roswell Park Cancer Institute
		Philip McCarthy, MD	Ph:  716-845-4074
			Email: philip.mccarthy@roswellpark.org

Registry Information
Official Title		Autologous Blood and Marrow Transplantation for Hematologic Malignancies and Selected Solid Tumors
Trial Start Date		2006-06-29
Trial Completion Date		2024-04-18 (estimated)
Registered in ClinicalTrials.gov		NCT00536601
Date Submitted to PDQ		2007-08-27
Information Last Verified		2008-11-30
NCI Grant/Contract Number		CA16056