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Auto Stem Cell Transplant for Lymphoma Patients

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ClinicalTrials.gov Identifier: NCT03125642
Recruitment Status : Recruiting
First Posted : April 24, 2017
Last Update Posted : September 25, 2019
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

Brief Summary:
This is a phase II study of autologous transplant for patients with Hodgkin (HL) and non-Hodgkin lymphomas (NHL) including those who are HIV positive.

Condition or disease Intervention/treatment Phase
Non-Hodgkin Lymphoma Hodgkin Lymphoma Drug: Etoposide Drug: BCNU Drug: AraC Drug: Melphalan Procedure: Peripheral blood stem cell transplantation Biological: G-CSF Drug: Cyclophosphamide Radiation: Total Body Irradiation Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Autologous Stem Cell Transplant In Patients With Hodgkin Lymphoma (HL) and Non-Hodgkin Lymphomas (NHL)
Actual Study Start Date : April 20, 2017
Estimated Primary Completion Date : April 30, 2023
Estimated Study Completion Date : April 30, 2026


Arm Intervention/treatment
Experimental: BEAM: NHL & HL
BCNU, etoposide, Ara-C and melphalan (BEAM) for all NHL and those HL patients who are unable to receive CBV
Drug: Etoposide
BEAM: 100 mg/m^2 IV over 2 hours BID on Days -5, -4, -3, -2 | CBV: 150 mg/m^2 intravenously over 4 hours every 12 hours starting at 6 a.m. and 6 p.m. on Days -6, -5, -4
Other Name: VP-16

Drug: BCNU
BEAM & CBV: 300 mg/m^2 IV over over 2 hours on Day -6
Other Name: Carmustine

Drug: AraC
BEAM: 100 mg/m^2 IV over 1 hour BID on Days -5, -4, -3, -2
Other Names:
  • Cytarabine
  • cytosine arabinoside
  • Cytosar-U
  • Depocyt

Drug: Melphalan
BEAM: 140 mg/m^2 IV over 20 minutes on Day -1
Other Name: Alkeran

Procedure: Peripheral blood stem cell transplantation
All Arms: Day 0 infuse PBSC. All patients will have PBSC collected by leukapheresis. Mobilization will be done with G-CSF.
Other Name: PBSC

Biological: G-CSF
All patients should receive G-CSF, 5 ug/kg/day IV as a bolus injection each evening beginning on day +5 until the ANC is >2500 x 10^9/L for 2 consecutive days. G-CSF will subsequently be restarted at 5 ug/kg/day SC or IV if the ANC falls below 1000/mm^3
Other Name: filgrastim

Experimental: CBV: HL
Cyclophosphamide, BCNU and VP-16 (CBV) for HL patients
Drug: Etoposide
BEAM: 100 mg/m^2 IV over 2 hours BID on Days -5, -4, -3, -2 | CBV: 150 mg/m^2 intravenously over 4 hours every 12 hours starting at 6 a.m. and 6 p.m. on Days -6, -5, -4
Other Name: VP-16

Drug: BCNU
BEAM & CBV: 300 mg/m^2 IV over over 2 hours on Day -6
Other Name: Carmustine

Drug: Cyclophosphamide
CBV: 1.5 gm/M^2 over 2 hours at 10 a.m. on Days -6, -5, -4, -3 | CY/TBI: 60 mg/kg IV over 2 hours on Days -7, -6
Other Name: Cytoxan

Experimental: CY/TBI
Cyclophosphamide/Total Body Irradiation (CY/TBI) for patients with recent history of CNS lymphoma or those with allergies/contra-indications to agents used in BEAM
Procedure: Peripheral blood stem cell transplantation
All Arms: Day 0 infuse PBSC. All patients will have PBSC collected by leukapheresis. Mobilization will be done with G-CSF.
Other Name: PBSC

Biological: G-CSF
All patients should receive G-CSF, 5 ug/kg/day IV as a bolus injection each evening beginning on day +5 until the ANC is >2500 x 10^9/L for 2 consecutive days. G-CSF will subsequently be restarted at 5 ug/kg/day SC or IV if the ANC falls below 1000/mm^3
Other Name: filgrastim

Drug: Cyclophosphamide
CBV: 1.5 gm/M^2 over 2 hours at 10 a.m. on Days -6, -5, -4, -3 | CY/TBI: 60 mg/kg IV over 2 hours on Days -7, -6
Other Name: Cytoxan

Radiation: Total Body Irradiation
CY/TBI: 165 cGy bid on Day -4, -3, -2, -1
Other Name: TBI




Primary Outcome Measures :
  1. Progression Free Survival Comparison [ Time Frame: 3 years post transplant ]
    Compare progression-free survival (PFS) at 3 years post-transplant for patients who received who received a radiation free preparative regimen to the prior study MT2004-24 where NHL subjects received total body irradiation (TBI) as part of their preparative regimen.


Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: 3 years post transplant ]
    Incidence of survival

  2. Treatment related mortality [ Time Frame: 6 months post transplant ]
    Incidence of treatment related mortality

  3. Treatment related mortality [ Time Frame: 1 year post transplant ]
    Incidence of treatment related mortality

  4. Secondary malignancies [ Time Frame: 3 years post transplant ]
    Cumulative incidence of secondary malignancies

  5. Neutrophil engraftment [ Time Frame: Day +1 to engraftment ]
    Average days to neutrophil engraftment

  6. Platelet engraftment [ Time Frame: Day +1 to engraftment ]
    Average days to platelet engraftment



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 75 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Eligible Diseases

    1. Non-Hodgkin's Lymphoma (NHL)

      • Patients with chemo-sensitive histologically confirmed NHL will be eligible for this treatment protocol contingent on histologic sub-classification.
      • Patients in partial or complete remission following cell therapy will also be eligible.
      • NHL patients with resistant or refractory lymphoma (no PR following up to three cycles of combination chemotherapy) will not be eligible for transplant in this trial.
      • Lymphoblastic Lymphoma:

        1. All patients will be eligible in second or greater complete remission (CR) or first or subsequent partial remission (PR)
        2. Patients with any high-risk features will be eligible in first complete remission
        3. High risk features include: Stage IV, LDH >2 x upper limit of normal, ≥ 2 extranodal sites
      • Mature B-cell Lymphoma

        1. Follicular Lymphoma and other indolent lymphoma in ≥ second CR2/PR2
        2. Diffuse Large B-Cell Lymphoma: in ≥ CR2 or ≥ PR1; a high intermediate or high IPI (≥ 2 for age-adjusted IPI or ≥3 for IPI) at diagnosis and double-hit or triple-hit lymphoma will be eligible in first CR; transformed lymphoma from FL (or other indolent lymphoma) or chronic lymphocytic leukemia will be eligible if chemosensitive and bone marrow is negative
        3. Mantle Cell Lymphoma: in first or greater CR or PR
        4. Burkitt's/Burkitt's like: all patients except localized lymphoma will be eligible any time after initial therapy (after achievement of first complete remission), or in partial remission if they fail to achieve CR; patients with localized (stage I or Ziegler stage A) will be eligible only if they fail to achieve CR1 or after relapse
      • Mature T-Cell Lymphoma

        1. Chemosensitive T-cell lymphomas including Primary T-cell not otherwise specified angioimmunoblastic, and ALK-positive anaplastic large cell, will be eligible after initial therapy, whether or not CR is achieved.
        2. Mycosis fungoides/Sezary syndrome will be eligible in ≥CR2/PR2
    2. Hodgkin Lymphoma (HL)

      • Patients with histologically proven HL will be eligible for transplantation after failing prior therapy.
      • Patients with resistant disease (initial or at relapse): those who fail to achieve an objective partial response to three cycles of combination non-cross resistant chemotherapy will not be eligible for transplant in this trial.
      • For stage I/II patients treated with primary chemotherapy-radiation, they must have failed (no CR or progression after CR) at least one salvage combination chemotherapy treatment regimen
      • For advanced (stage III/IV) Hodgkin disease, patients must have failed an Adriamycin containing regimen (ABVD) or an alternative non-cross resistant regimen (e.g. MOPP)
      • Patients with any high-risk features will also be eligible, including those who:

        1. fail to achieve complete remission with initial combination chemotherapy
        2. have bulky disease after initial therapy (chemotherapy or radiation) defined as residual mediastinal mass ≥ 5 cm or other residual mass ≥ 10 cm accompanied by other features of persisting disease (e.g., PET scan positive; high LDH; enlarging on serial x-rays or biopsy positive) will be eligible - if feasible, persistent disease should be proven by biopsy
      • Patients should receive chemotherapy to attempt to achieve CR or minimal disease state for all patients pre-transplantation. The use of up to three cycles of non-cross resistant combination chemotherapy is advised.
      • Residual areas of limited disease should be considered for radiotherapy after and not prior to transplantation.
    3. HIV positive patients who are otherwise eligible for this study may be enrolled if they meet the following requirements:

      • Are seen in the infectious disease (ID)/HIV clinic prior to enrollment on study for the purpose of determining eligibility and for local coordination of HIV care during the peri-transplant period.
      • Are on maximally active anti-HIV regimen to control disease as determined appropriate by the ID/HIV physicians. For the majority of patients, this will be a highly active anti-retroviral therapy (HAART)-type therapy including a protease inhibitor.
      • CD4+ ≥ 50/µL
      • HIV RNA viral load ≤ 100,000 copies per mL on each of samples 4 weeks apart. The most recent level must be within 30 days of enrollment.
  • Performance Status: Karnofsky Performance Status ≥ 80% for patients ≥ 16 years of age or Lansky Play Score ≥ 80 for patients < 16 years of age. Note: if poor performance status is due to lymphoma - KPS ≥ 60% or LPS ≥ 60 is acceptable
  • Organ Function

    1. No evidence of serious organ dysfunction that is not attributable to tumor including:

    1. Hematologic:

      • hemoglobin > 8 gm/dL
      • WBC > 2.5 x 109/L with an ANC > 1.5 x 109/L off G-CSF or GM-CSF for 10 days or Neulasta for 21 days
      • platelets > 100 x 109/L without transfusion
      • bone marrow cellularity of > 20% with <5% involvement with tumor
    2. Renal: GFR > 50 ml/min/1.73m2 or serum creatinine ≤ 2.5 x ULN for age
    3. Hepatic: no history of severe prior or ongoing chronic liver disease. Total bilirubin ≤ 2.0 mg/dl, AST and alkaline phosphatase <5x upper limit of normal
    4. Cardiac: free of symptoms of uncontrolled cardiac disease including unstable angina, decompensated congestive heart failure, or arrhythmia. The ejection fraction by gated cardiac blood flow scan (MUGA) or Echocardiogram must be >40%
    5. Pulmonary: no significant obstructive airways disease (FEV1 must be ≥ 50%) and must have acceptable diffusion capacity (corrected DLCO > 50% of predicted)
    6. Central Nervous System: Patients with a history of CNS involvement by lymphoma or with relapsed primary CNS lymphoma will be eligible for Cy/TBI arm. Patients with active CNS disease are eligible if they have completed a standard treatment for CNS lymphoma and have no evidence of progressive CNS disease at the time of enrollment
  • Other Inclusion Criteria

    1. At least 4 weeks from previous chemotherapy; 6 weeks from nitrosoureas
    2. Women of child bearing potential and sexually active males with partners of child bearing potential must agree to use adequate birth control for the duration of treatment
    3. Patients who are carriers of Hepatitis B will be included in this study
    4. Voluntary written consent

Exclusion Criteria:

  • Pregnant or breastfeeding: Females of childbearing potential must have a blood test or urine study within 14 days prior to registration to rule out pregnancy
  • Eligible for any higher priority transplant protocols
  • Chemotherapy resistant disease
  • Unrelated active infection

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03125642


Contacts
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Contact: Timothy Krepski 612-273-2800 tkrepsk1@fairview.org

Locations
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United States, Minnesota
Masonic Cancer Center, University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Timothy Krepski    612-273-2800    tkrepsk1@fairview.org   
Principal Investigator: Veronika Bachanova, MD         
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
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Principal Investigator: Veronika Bachanova, MD Masonic Cancer Center, University of Minnesota

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Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT03125642     History of Changes
Other Study ID Numbers: 2016LS132
MT2016-11C ( Other Identifier: Masonic Cancer Center, University of Minnesota )
First Posted: April 24, 2017    Key Record Dates
Last Update Posted: September 25, 2019
Last Verified: September 2019

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Masonic Cancer Center, University of Minnesota:
Lymphoblastic Lymphoma
Mature B-cell Lymphomas
Follicular Lymphoma
Diffuse Large B-Cell Lymphoma
Mantle Cell Lymphoma
Burkitt's/Burkitt's like
Mature T-Cell Lymphoma
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Melphalan
Etoposide
Etoposide phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors