Auto Stem Cell Transplant for Lymphoma Patients

• ClinicalTrials.gov Identifier: NCT03125642
• Recruitment Status: Recruiting
• First Posted: April 24, 2017
• Last Update Posted: January 26, 2023
• Sponsor: Masonic Cancer Center, University of Minnesota
• Information provided by (Responsible Party): Masonic Cancer Center, University of Minnesota

Study Description

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

Study Design

• 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

Arms and Interventions

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

Outcome Measures

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

Eligibility Criteria

• 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

Contacts and Locations

Contacts

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

Locations

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

• Principal Investigator: Veronika Bachanova, MD; Masonic Cancer Center, University of Minnesota

More Information

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT03125642
• Other Study ID Numbers: 2016LS132; MT2016-11C ( Other Identifier: Masonic Cancer Center, University of Minnesota )
• First Posted: April 24, 2017
• Last Update Posted: January 26, 2023
• Last Verified: January 2023

• 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:

Lymphoma; Lymphoma, Non-Hodgkin; Hodgkin Disease; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Cytarabine; Cyclophosphamide; Melphalan; Carmustine; Etoposide; 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; Antimetabolites, Antineoplastic; Antimetabolites; Antiviral Agents