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

NCT00574496 | Completed Phase 2 Results

• 2 other identifiers: 07-147MSKCC-07147
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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.

Conditions

Lymphoma

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival at 1 Year

  Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions

  1 year

Secondary Outcomes (2)

• Overall Survival

  up to 8 years

• Disease Relapse or Progression as Measured by CT Scan or PET

  3 years

Study Arms (1)

High-Risk or Relapsed Hodgkin Lymphoma

EXPERIMENTAL

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

Interventions

cyclophosphamide DRUG

High-Risk or Relapsed Hodgkin Lymphoma

cyclosporine DRUG

High-Risk or Relapsed Hodgkin Lymphoma

fludarabine phosphate DRUG

High-Risk or Relapsed Hodgkin Lymphoma

gemcitabine hydrochloride DRUG

High-Risk or Relapsed Hodgkin Lymphoma

ifosfamide DRUG

High-Risk or Relapsed Hodgkin Lymphoma

mechlorethamine hydrochloride DRUG

High-Risk or Relapsed Hodgkin Lymphoma

melphalan DRUG

High-Risk or Relapsed Hodgkin Lymphoma

methotrexate DRUG

High-Risk or Relapsed Hodgkin Lymphoma

mycophenolate mofetil DRUG

High-Risk or Relapsed Hodgkin Lymphoma

prednisone DRUG

High-Risk or Relapsed Hodgkin Lymphoma

procarbazine hydrochloride DRUG

High-Risk or Relapsed Hodgkin Lymphoma

vincristine sulfate DRUG

High-Risk or Relapsed Hodgkin Lymphoma

vinorelbine tartrate DRUG

High-Risk or Relapsed Hodgkin Lymphoma

allogeneic bone marrow transplantation PROCEDURE

High-Risk or Relapsed Hodgkin Lymphoma

allogeneic hematopoietic stem cell transplantation PROCEDURE

High-Risk or Relapsed Hodgkin Lymphoma

nonmyeloablative allogeneic hematopoietic stem cell transplantation PROCEDURE

High-Risk or Relapsed Hodgkin Lymphoma

peripheral blood stem cell transplantation PROCEDURE

High-Risk or Relapsed Hodgkin Lymphoma

umbilical cord blood transplantation PROCEDURE

High-Risk or Relapsed Hodgkin Lymphoma

total-body irradiation RADIATION

High-Risk or Relapsed Hodgkin Lymphoma

Eligibility Criteria

• Age: 13 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Lymphoma; Hodgkin Disease; Recurrence

Interventions

Cyclophosphamide; Cyclosporine; fludarabine phosphate; Gemcitabine; Ifosfamide; Mechlorethamine; Melphalan; Methotrexate; Mycophenolic Acid; Prednisone; Procarbazine; Vincristine; Vinorelbine; Peripheral Blood Stem Cell Transplantation; Cord Blood Stem Cell Transplantation; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Oxazines; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Benzamides; Amides; Benzoates; Acids, Carbocyclic; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Radiotherapy; Investigative Techniques

Results Point of Contact

• Title: Dr. Miguel-Angel Perales, MD
• Organization: Memorial Sloan Kettering Cancer Center

peralesm@mskcc.org

646-608-3757

Study Officials

• Miguel-Angel Perales, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

• Juliet Barker, MBBS

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

• Tanya Trippett, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2007
• First Posted: December 17, 2007
• Study Start: November 13, 2007
• Primary Completion: August 2, 2022
• Study Completion: August 2, 2022
• Last Updated: September 28, 2023
• Results First Posted: September 28, 2023

Record last verified: 2022-10

Locations

US (1)