Combination Chemotherapy Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or High-Risk Primary Refractory Hodgkin Lymphoma
|ClinicalTrials.gov Identifier: NCT00574496|
Recruitment Status : Active, not recruiting
First Posted : December 17, 2007
Last Update Posted : May 3, 2017
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 or disease||Intervention/treatment||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|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||November 2007|
|Estimated Primary Completion Date :||November 2018|
|Estimated Study Completion Date :||November 2018|
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|
- Progression-free survival at 1 year [ Time Frame: 1 year ]
- 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 ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00574496
|United States, New York|
|Memorial Sloan-Kettering Cancer Center|
|New York, New York, United States, 10065|
|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|