S0410 Tandem Stem Cell Transplantation in Treating Patients With Progressive or Recurrent Hodgkin's Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00233987
First received: October 5, 2005
Last updated: February 21, 2014
Last verified: February 2014
  Purpose

RATIONALE: Radiation therapy uses high-energy x-rays to kill cancer cells. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy with a peripheral stem cell transplant may allow more chemotherapy to be given so that more cancer cells are killed. Tandem (two) autologous stem cell transplants may be an effective treatment for Hodgkin's lymphoma.

PURPOSE: This phase II trial is studying how well tandem stem cell transplantation works in treating patients with progressive or recurrent Hodgkin's lymphoma.


Condition Intervention Phase
Lymphoma
Drug: carmustine
Drug: cyclophosphamide
Drug: etoposide
Drug: melphalan
Procedure: autologous-autologous tandem hematopoietic stem cell transplantation
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Tandem Autologous Stem Cell Transplantation for Patients With Primary Progressive or Recurrent Hodgkin's Disease (A BMT Study), Phase II

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • 2-year Progression-free Survival [ Time Frame: At day 60, then every 6 months for 2 years ] [ Designated as safety issue: No ]
    Measured from date of randomization to date of first observation of progressive disease, or death due to any cause


Secondary Outcome Measures:
  • Response Rate [ Time Frame: At day 60, then every 6 months for 2 years ] [ Designated as safety issue: No ]
    Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM. Partial Response(PR) is a 50% decrease in the sum of products of greatest diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes.

  • Overall Survival [ Time Frame: At day 60, then every 6 months for 2 years, then annually for a total of 7 years ] [ Designated as safety issue: No ]
    Measured from date of registration to date of death due to any cause or last contact

  • Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug [ Time Frame: Assessed after cycle 1 high dose therapy, after cycle 2 high dose therapy, and at 1 month and 2 months after the second stem cell infusion ] [ Designated as safety issue: Yes ]
    Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal.


Enrollment: 98
Study Start Date: October 2005
Estimated Study Completion Date: February 2016
Primary Completion Date: February 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: High-dose therapy plus tandem transplant
Regimen consists of 2 cycles of high-dose therapy, each followed by stem cell infusion. Cycle 1 consists of high-dose melphalan followed by infusion of approximately 1.5 million cluster of differentiation 34 positive (CD34+) cells. Cycle 2 consists of either TBI-based or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)-based high-dose therapy followed by infusion of at least 2 million CD34+ cells.
Drug: carmustine
150 mg/m^2 IV over 2 hours 4, 5, and 6 days before transplant.
Other Name: BCNU
Drug: cyclophosphamide
100 mg/kg IV 2 days before transplant.
Drug: etoposide
60 mg/kg IV over 4 hours 4 days before transplant.
Drug: melphalan
150 mg/m^2 IV 1 day before transplant.
Procedure: autologous-autologous tandem hematopoietic stem cell transplantation
2.0 x 10^6 CD34+ cells, beginning at least 24 hours after melphalan infusion.
Radiation: radiation therapy
150 centigray (cGy) total body irradiation given b.i.d on days 5-8 before transplant.
Other Name: Total body irradiation (TBI)

Detailed Description:

OBJECTIVES:

  • Determine the 2-year progression-free survival of patients with progressive or recurrent Hodgkin's lymphoma treated with tandem autologous stem cell transplantation (2 courses of high-dose therapy with autologous stem cell rescue).
  • Determine the response rate in patients treated with this regimen.
  • Determine the toxic effects of this regimen in these patients.

OUTLINE: This is a multicenter study.

  • Salvage therapy (for patients with relapsed disease after achieving a previous complete response): Patients receive at least 2 courses of salvage chemotherapy or radiotherapy. No more than 6 weeks later, patients proceed to autologous hematopoietic stem cell collection.
  • Autologous hematopoietic stem cell collection: Patients undergo autologous hematopoietic stem cell collection. Patients with an inadequate number of collected stem cells are removed from the study.
  • Pre-transplant salvage radiation: Patients with residual tumor greater than 5 cm after initial salvage therapy undergo involved-field radiotherapy. All patients then proceed to the first preparative regimen.
  • First preparative regimen: Patients receive high-dose melphalan IV on day -1.
  • First autologous stem cell transplantation (SCT): Patients undergo autologous SCT on day 0. At least 28 days later, patients proceed to second preparative regimen.
  • Second preparative regimen: Patients receive 1 of the following preparative regimens:

    • Total-body irradiation (TBI)-based regimen: Patients undergo TBI twice daily on days -8 to -5. Patients also receive etoposide IV over 4 hours on day -4 and cyclophosphamide IV over 1 hour on day -2.
    • Carmustine-based regimen: Patients receive carmustine IV over 2 hours on days -6 to -4, etoposide IV over 4 hours on day -4, and cyclophosphamide IV over 1 hour on day -2.
  • Second autologous SCT: Patients undergo second autologous SCT on day 0. After completion of study treatment, patients are followed every 6 months for 2 years and then annually for up to 7 years.

PROJECTED ACCRUAL: A total of 85 patients will be accrued for this study over 2 years.

  Eligibility

Ages Eligible for Study:   15 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically or cytologically confirmed Hodgkin's lymphoma

    • Relapsed or refractory disease
    • Biopsy or radiological evidence of disease at time of recurrence/progression required
  • Has received ≥ 1 prior systemic chemotherapy regimen
  • No clonal abnormalities in marrow collection
  • Must undergo involved-field radiotherapy if bulky disease > 5 cm
  • Must have adequate sections of original diagnostic specimen available for review

    • Needle aspirations or cytologies are not adequate
  • No prior lymphoma, myelodysplastic syndromes, or leukemia (even if disease free > 5 years)
  • Patients who relapse after achieving a complete remission must complete a minimum of 2 courses of salvage chemotherapy or radiation therapy to determine if sensitive or resistant recurrent disease is present
  • No central nervous system (CNS) involvement

PATIENT CHARACTERISTICS:

Age

  • 15 to 70

Performance status

  • Zubrod 0-2

Life expectancy

  • Not specified

Hematopoietic

  • Absolute neutrophil count ≥ 1,500/mm^3

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN) (unless due to Hodgkin's disease)

Renal

  • Creatinine clearance ≥ 60 mL/min
  • Creatinine ≤ 2 times upper limit of normal

Cardiovascular

  • None of the following conditions requiring therapy:

    • Coronary artery disease
    • Cardiomyopathy
    • Congestive heart failure
    • Arrhythmias
  • Ejection fraction ≥ 45% by Multi Gated Acquisition Scan (MUGA) or 2-D echocardiogram

Pulmonary

  • Adequate pulmonary function
  • Corrected diffusing capacity of lung for carbon monoxide (DLCO) ≥ 60% OR
  • Forced Expiratory Volume in One Side (FEV_1) ≥ 60% of predicted

Other

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer
  • No known HIV or AIDS infection
  • No active bacterial, fungal, or viral infection
  • No medical condition that would preclude study treatment

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • See Disease Characteristics

Endocrine therapy

  • Not specified

Radiotherapy

  • See Disease Characteristics

Surgery

  • Not specified
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00233987

  Show 53 Study Locations
Sponsors and Collaborators
Southwest Oncology Group
Investigators
Study Chair: Eileen P. Smith, MD Beckman Research Institute
Study Chair: Patrick J. Stiff, MD Loyola University
Study Chair: Louis S. Constine, MD James P. Wilmot Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00233987     History of Changes
Other Study ID Numbers: CDR0000442392, U10CA032102, S0410
Study First Received: October 5, 2005
Results First Received: January 2, 2013
Last Updated: February 21, 2014
Health Authority: United States: Federal Government

Keywords provided by Southwest Oncology Group:
recurrent adult Hodgkin lymphoma

Additional relevant MeSH terms:
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Melphalan
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on September 16, 2014