Auto Stem Cell Transplant for Lymphoma Patients
Study Details
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 |
|---|---|---|
|
Phase 2 |
Study Design
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 Names:
Drug: BCNU
BEAM & CBV: 300 mg/m^2 IV over over 2 hours on Day -6
Other Names:
Drug: AraC
BEAM: 100 mg/m^2 IV over 1 hour BID on Days -5, -4, -3, -2
Other Names:
Drug: Melphalan
BEAM: 140 mg/m^2 IV over 20 minutes on Day -1
Other Names:
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 Names:
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 Names:
|
| 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 Names:
Drug: BCNU
BEAM & CBV: 300 mg/m^2 IV over over 2 hours on Day -6
Other Names:
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 Names:
|
| 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 Names:
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 Names:
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 Names:
Radiation: Total Body Irradiation
CY/TBI: 165 cGy bid on Day -4, -3, -2, -1
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Progression Free Survival Comparison [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
- Overall Survival [3 years post transplant]
Incidence of survival
- Treatment related mortality [6 months post transplant]
Incidence of treatment related mortality
- Treatment related mortality [1 year post transplant]
Incidence of treatment related mortality
- Secondary malignancies [3 years post transplant]
Cumulative incidence of secondary malignancies
- Neutrophil engraftment [Day +1 to engraftment]
Average days to neutrophil engraftment
- Platelet engraftment [Day +1 to engraftment]
Average days to platelet engraftment
Eligibility Criteria
Criteria
Inclusion Criteria:
- Eligible Diseases
- 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:
-
All patients will be eligible in second or greater complete remission (CR) or first or subsequent partial remission (PR)
-
Patients with any high-risk features will be eligible in first complete remission
-
High risk features include: Stage IV, LDH >2 x upper limit of normal, ≥ 2 extranodal sites
- Mature B-cell Lymphoma
-
Follicular Lymphoma and other indolent lymphoma in ≥ second CR2/PR2
-
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
-
Mantle Cell Lymphoma: in first or greater CR or PR
-
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
-
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.
-
Mycosis fungoides/Sezary syndrome will be eligible in ≥CR2/PR2
-
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:
-
fail to achieve complete remission with initial combination chemotherapy
-
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.
- 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
-
No evidence of serious organ dysfunction that is not attributable to tumor including:
-
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
-
Renal: GFR > 50 ml/min/1.73m2 or serum creatinine ≤ 2.5 x ULN for age
-
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
-
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%
-
Pulmonary: no significant obstructive airways disease (FEV1 must be ≥ 50%) and must have acceptable diffusion capacity (corrected DLCO > 50% of predicted)
-
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
-
At least 4 weeks from previous chemotherapy; 6 weeks from nitrosoureas
-
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
-
Patients who are carriers of Hepatitis B will be included in this study
-
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
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Masonic Cancer Center, University of Minnesota | Minneapolis | Minnesota | United States | 55455 |
Sponsors and Collaborators
- Masonic Cancer Center, University of Minnesota
Investigators
- Principal Investigator: Veronika Bachanova, MD, Masonic Cancer Center, University of Minnesota
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2016LS132
- MT2016-11C