Auto Stem Cell Transplant for Lymphoma Patients

NCT ID: NCT03125642

Last Updated: 2025-11-04

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-20
• Study Completion Date: 2027-04-30

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.

Conditions

Non-Hodgkin Lymphoma; Hodgkin Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

BEAM: NHL & HL

BCNU, etoposide, Ara-C and melphalan (BEAM) for all NHL and those HL patients who are unable to receive CBV

Group Type: EXPERIMENTAL

Etoposide

Intervention Type: DRUG

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

BCNU

Intervention Type: DRUG

BEAM \& CBV: 300 mg/m\^2 IV over over 2 hours on Day -6

AraC

Intervention Type: DRUG

BEAM: 100 mg/m\^2 IV over 1 hour BID on Days -5, -4, -3, -2

Melphalan

Intervention Type: DRUG

BEAM: 140 mg/m\^2 IV over 20 minutes on Day -1

Peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

All Arms: Day 0 infuse PBSC. All patients will have PBSC collected by leukapheresis. Mobilization will be done with G-CSF.

G-CSF

Intervention Type: BIOLOGICAL

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

CBV: HL

Cyclophosphamide, BCNU and VP-16 (CBV) for HL patients

Group Type: EXPERIMENTAL

Etoposide

Intervention Type: DRUG

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

BCNU

Intervention Type: DRUG

BEAM \& CBV: 300 mg/m\^2 IV over over 2 hours on Day -6

Cyclophosphamide

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

All Arms: Day 0 infuse PBSC. All patients will have PBSC collected by leukapheresis. Mobilization will be done with G-CSF.

G-CSF

Intervention Type: BIOLOGICAL

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

Cyclophosphamide

Intervention Type: DRUG

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

Total Body Irradiation

Intervention Type: RADIATION

CY/TBI: 165 cGy bid on Day -4, -3, -2, -1

Interventions

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

Intervention Type: DRUG

BCNU

BEAM \& CBV: 300 mg/m\^2 IV over over 2 hours on Day -6

Intervention Type: DRUG

AraC

BEAM: 100 mg/m\^2 IV over 1 hour BID on Days -5, -4, -3, -2

Intervention Type: DRUG

Melphalan

BEAM: 140 mg/m\^2 IV over 20 minutes on Day -1

Intervention Type: DRUG

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.

Intervention Type: PROCEDURE

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

Intervention Type: BIOLOGICAL

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

Intervention Type: DRUG

Total Body Irradiation

CY/TBI: 165 cGy bid on Day -4, -3, -2, -1

Intervention Type: RADIATION

Other Intervention Names

VP-16; Carmustine; Cytarabine; cytosine arabinoside; Cytosar-U; Depocyt; Alkeran; PBSC; filgrastim; Cytoxan; TBI

Eligibility 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

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

• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Veronika Bachanova, MD

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Timothy Krepski

Role: CONTACT

tkrepsk1@fairview.org

612-273-2800

Facility Contacts

Timothy Krepski

Role: primary

tkrepsk1@fairview.org

612-273-2800

Other Identifiers

MT2016-11C

Identifier Type: OTHER

Identifier Source: secondary_id

2016LS132

Identifier Type: -

Identifier Source: org_study_id