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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT00574496
First received: December 14, 2007
Last updated: October 19, 2016
Last verified: October 2016
  Purpose

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.


Condition Intervention Phase
Lymphoma
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
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan Kettering Cancer Center:

Primary Outcome Measures:
  • Progression-free survival at 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Survival after 1 year [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Failure of neutrophil recovery and/or donor engraftment [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Graft versus-host disease measured weekly during the first 100 days of treatment [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Transplant-related mortality measured 180 days after transplantation [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Disease relapse or progression as measured by CT scan or PET [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Immunologic recovery [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 30
Study Start Date: November 2007
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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

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.

  Eligibility

Ages Eligible for Study:   13 Years to 65 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00574496

Locations
United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
National Cancer Institute (NCI)
Investigators
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
  More Information

Additional Information:
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT00574496     History of Changes
Other Study ID Numbers: 07-147  MSKCC-07147 
Study First Received: December 14, 2007
Last Updated: October 19, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by Memorial Sloan Kettering Cancer Center:
recurrent adult Hodgkin lymphoma
recurrent/refractory childhood Hodgkin lymphoma
adult lymphocyte depletion Hodgkin lymphoma
adult nodular sclerosis Hodgkin lymphoma
adult mixed cellularity Hodgkin lymphoma
childhood lymphocyte depletion Hodgkin lymphoma
childhood mixed cellularity Hodgkin lymphoma
childhood nodular sclerosis Hodgkin lymphoma
stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
stage III childhood Hodgkin lymphoma
stage IV childhood Hodgkin lymphoma

Additional relevant MeSH terms:
Lymphoma
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Prednisone
Gemcitabine
Fludarabine
Vinorelbine
Fludarabine phosphate
Cyclophosphamide
Vincristine
Methotrexate
Melphalan
Mycophenolic Acid
Mechlorethamine
Procarbazine
Ifosfamide
Cyclosporins
Cyclosporine
Mycophenolate mofetil
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal

ClinicalTrials.gov processed this record on December 02, 2016