Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Combination Chemotherapy Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or High-Risk Primary Refractory Hodgkin Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00574496
Recruitment Status : Active, not recruiting
First Posted : December 17, 2007
Last Update Posted : May 6, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center

Tracking Information
First Submitted Date  ICMJE December 14, 2007
First Posted Date  ICMJE December 17, 2007
Last Update Posted Date May 6, 2019
Actual Study Start Date  ICMJE November 2007
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 11, 2012)
Progression-free survival at 1 year [ Time Frame: 1 year ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 14, 2007)
Progression-free survival at 1 year
Change History Complete list of historical versions of study NCT00574496 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 11, 2012)
  • Survival after 1 year [ Time Frame: 1 year ]
  • Failure of neutrophil recovery and/or donor engraftment [ Time Frame: 1 year ]
  • Graft versus-host disease measured weekly during the first 100 days of treatment [ Time Frame: 1 year ]
  • Transplant-related mortality measured 180 days after transplantation [ Time Frame: 1 year ]
  • Disease relapse or progression as measured by CT scan or PET [ Time Frame: 1 year ]
  • Immunologic recovery [ Time Frame: 1 year ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 14, 2007)
  • Survival after 1 year
  • Failure of neutrophil recovery and/or donor engraftment
  • Graft versus-host disease measured weekly during the first 100 days of treatment
  • Transplant-related mortality measured 180 days after transplantation
  • Disease relapse or progression as measured by CT scan or PET
  • Immunologic recovery
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Combination Chemotherapy Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or High-Risk Primary Refractory Hodgkin Lymphoma
Official Title  ICMJE An Intention-to-Treat Study of Salvage Chemotherapy Followed by Allogeneic Hematopoietic Stem Cell Transplant for the Treatment of High-Risk or Relapsed Hodgkin Lymphoma
Brief Summary

RATIONALE: Giving chemotherapy before a donor stem cell transplant helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving cyclosporine, mycophenolate mofetil, and methotrexate before and after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well combination chemotherapy followed by donor stem cell transplant works in treating patients with relapsed or high-risk primary refractory Hodgkin lymphoma.

Detailed Description

OUTLINE: Patients are stratified according to response to prior therapy and risk factors (those with presence of all 3 risk factors and failed primary therapy or primary progressive disease vs. patients who relapse more than 100 days after an autologous stem cell transplant).

  • Salvage chemotherapy (IGV or MOPP): Patients who have previously received mechlorethamine hydrochloride receive IGV; patients who have previously received a gemcitabine-based regimen receive MOPP.

    • IGV (ifosfamide, gemcitabine hydrochloride, and vinorelbine ditartrate): Patients receive IGV combination chemotherapy comprising ifosfamide IV on days 1-4, gemcitabine hydrochloride IV on days 1 and 4, and vinorelbine ditartrate IV on day 1. Treatment repeats every 2-3 weeks for 2-3 courses in the absence of disease progression or unacceptable toxicity.
    • MOPP (mechlorethamine hydrochloride, vincristine, procarbazine hydrochloride, and prednisone): Patients receive MOPP combination chemotherapy comprising mechlorethamine hydrochloride IV on days 1 and 8, vincristine IV on days 1 and 8, oral procarbazine hydrochloride on days 1-14, and oral prednisone on days 1-14. Treatment repeats every 4 weeks for at least 2 courses in the absence of disease progression or unacceptable toxicity.

Patients with no progression of disease after salvage chemotherapy (at allograft work-up) proceed to allogeneic hematopoietic stem cell transplantation [AHSCT]* within 60 days after completion of salvage chemotherapy.

NOTE: *Patients with a nodal mass > 5 cm that has not ben previously irradiated and in the absence of extranodal disease may undergo involved-field radiotherapy twice daily for 2 weeks, prior to AHSCT.

  • AHSCT with reduced-intensity or non-myeloablative conditioning: Patients achieving partial response or stable disease after salvage therapy receive fludarabine phosphate IV over 30 minutes on days -6 to -2; melphalan IV over 15 minutes on days -6 and -5; and undergo AHSCT on day 0 (reduced-intensity conditioning). Patients achieving complete response after salvage therapy receive fludarabine phosphate IV over 30 minutes on days -6 to -2; cyclophosphamide IV over 15 minutes on day -6; total-body irradiation over 20-30 minutes on day -1; and undergo AHSCT on day 0 (non-myeloablative conditioning).
  • Graft-vs-host disease prophylaxis: Patients with related or unrelated donors receive cyclosporine IV over 2-4 hours or orally on days -3 to 100 followed by a taper, mycophenolate mofetil IV or orally on days -3 to 46 followed by a taper, and methotrexate IV on days 1, 3, 6, and 11.

Patients who received umbilical cord blood receive cyclosporine and mycophenolate mofetil as above (no methotrexate).

Follow-up period of 2 years post-transplant.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Lymphoma
Intervention  ICMJE
  • Drug: cyclophosphamide
  • Drug: cyclosporine
  • Drug: fludarabine phosphate
  • Drug: gemcitabine hydrochloride
  • Drug: ifosfamide
  • Drug: mechlorethamine hydrochloride
  • Drug: melphalan
  • Drug: methotrexate
  • Drug: mycophenolate mofetil
  • Drug: prednisone
  • Drug: procarbazine hydrochloride
  • Drug: vincristine sulfate
  • Drug: vinorelbine tartrate
  • Procedure: allogeneic bone marrow transplantation
  • Procedure: allogeneic hematopoietic stem cell transplantation
  • Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
  • Procedure: peripheral blood stem cell transplantation
  • Procedure: umbilical cord blood transplantation
  • Radiation: total-body irradiation
Study Arms  ICMJE Experimental: High-Risk or Relapsed Hodgkin Lymphoma
This is a phase 2 intention-to-treat study of salvage chemotherapy followed by allogeneic HSC transplant for the treatment of primary refractory or relapsed HL. Patients who 1) do not progress on salvage chemotherapy, and 2) have both suitable HSC donors and 3) a satisfactory pre-allograft work-up will proceed to allograft. Patients who fail any of these 3 criteria will be off-study and considered treatment failures for the purposes of the intention-to-treat study.
Interventions:
  • Drug: cyclophosphamide
  • Drug: cyclosporine
  • Drug: fludarabine phosphate
  • Drug: gemcitabine hydrochloride
  • Drug: ifosfamide
  • Drug: mechlorethamine hydrochloride
  • Drug: melphalan
  • Drug: methotrexate
  • Drug: mycophenolate mofetil
  • Drug: prednisone
  • Drug: procarbazine hydrochloride
  • Drug: vincristine sulfate
  • Drug: vinorelbine tartrate
  • Procedure: allogeneic bone marrow transplantation
  • Procedure: allogeneic hematopoietic stem cell transplantation
  • Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
  • Procedure: peripheral blood stem cell transplantation
  • Procedure: umbilical cord blood transplantation
  • Radiation: total-body irradiation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: September 11, 2012)
30
Original Enrollment  ICMJE
 (submitted: December 14, 2007)
62
Estimated Study Completion Date  ICMJE November 2020
Estimated Primary Completion Date November 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

DISEASE CHARACTERISTICS:

  • Histologically confirmed classical Hodgkin lymphoma, including CD20+ disease

    • No lymphocyte predominant histology
  • Primary refractory or relapsed disease with all 3 risk factors, failed platinum-based chemotherapy, or disease relapsed more than 100 days after autologous stem cell transplantation, proven by biopsy or fine-needle aspiration (cytology) of an involved site

    • Risk factors are defined as B-symptoms, extranodal sites of disease, and disease remission lasting < 1 year after first-line therapy
  • Failed doxorubicin hydrochloride or mechlorethamine hydrochloride-containing front-line therapy
  • Fludeoxyglucose F 18-PET scan demonstrating PET-avid disease
  • No more than 2 prior salvage chemotherapy regimens (for patients proceed to allogeneic hematopoietic stem cell transplantation [AHSCT])
  • Donor available meeting 1 of the following criteria (for patients proceed to AHSCT):

    • HLA-matched or one allele mismatched related donor

      • Genotypically or phenotypically matched at ≥ 9/10 of the A, B, C, DRB1, and DQB1 loci, as tested by high resolution
      • Peripheral blood stem cells (PBSC) collected
    • HLA-matched unrelated donor

      • Matched at ≥ 9/10 (allele mismatch only) of the A, B, C, DRB1, and DQB1 loci, as tested by high resolution
      • PBSC or bone marrow collected
    • Umbilical cord blood (2 units)

      • must be ≥ 4/6 HLA-A, B antigen, and DRB1 allele matched with recipient

PATIENT CHARACTERISTICS:

  • Platelet count > 50,000/mm^3
  • ANC > 1,000/mm^3
  • Cardiac ejection fraction > 50% (for patients ≥ 18 years of age)
  • Fractional shortening > 50% by echocardiogram* (for patients < 18 years of age)
  • Adjusted diffusing capacity > 50% on pulmonary function testing*
  • Serum creatinine < 1.5 mg/dL
  • Creatinine clearance ≥ 50 mL/min
  • Total bilirubin < 2.0 mg/dL in the absence of a history of Gilbert disease
  • HIV I and II negative
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Karnofsky performance status (PS) ≥ 70% or Lansky PS ≥ 70% (for patients proceed to AHSCT)
  • No active and uncontrolled infection at time of transplantation including active infection with Aspergillus or other mold (for patients proceed to AHSCT) NOTE: *measured since last chemotherapy

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • No prior allogeneic transplantation
  • No more than 1 prior autologous transplantation
  • No inability to complete planned cytoreduction due to therapy complications
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 13 Years to 65 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00574496
Other Study ID Numbers  ICMJE 07-147
MSKCC-07147
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Memorial Sloan Kettering Cancer Center
Study Sponsor  ICMJE Memorial Sloan Kettering Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Miguel-Angel Perales, MD Memorial Sloan Kettering Cancer Center
Principal Investigator: Juliet Barker, MBBS Memorial Sloan Kettering Cancer Center
Principal Investigator: Craig Moskowitz, MD Memorial Sloan Kettering Cancer Center
Principal Investigator: Tanya Trippett, MD Memorial Sloan Kettering Cancer Center
PRS Account Memorial Sloan Kettering Cancer Center
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP