Auto Stem Cell Transplant for Lymphoma

Recruiting in Palo Alto (17 mi)

Overseen by Veronika Bachanova, MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Masonic Cancer Center, University of Minnesota

Must be taking: Anti-HIV therapy

Disqualifiers: Pregnancy, Chemotherapy resistance, Active infection, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are HIV positive, you must be on a maximally active anti-HIV regimen as determined by your doctor.

What data supports the effectiveness of the treatment Auto Stem Cell Transplant for Lymphoma?

Research shows that high-dose chemotherapy followed by autologous stem cell transplantation is effective for treating relapsed or refractory Hodgkin and non-Hodgkin lymphoma, with studies reporting high survival rates and disease-free progression. The BEAM regimen, which includes carmustine and melphalan, is commonly used and has shown similar effectiveness to other regimens with potentially less toxicity. ^{1 2 3 4 5}

Is the auto stem cell transplant for lymphoma generally safe for humans?

The safety of auto stem cell transplants for lymphoma has been studied, showing that while effective, high-dose chemotherapy regimens can lead to significant side effects. These include organ toxicity, such as liver and kidney issues, and other complications like mucositis (painful inflammation and ulceration of the mucous membranes lining the digestive tract). However, newer formulations like EVOMELA have shown an acceptable safety profile with reduced complications. ^{3 6 7 8 9}

How is the Auto Stem Cell Transplant for Lymphoma treatment different from other treatments?

This treatment is unique because it combines high-dose chemotherapy with drugs like BCNU (carmustine), cyclophosphamide, and melphalan, along with total body irradiation and peripheral blood stem cell transplantation, which helps restore the patient's blood cells after intensive treatment. This approach is particularly used for patients with relapsed or refractory lymphoma, offering a comprehensive strategy to eliminate cancer cells and support recovery. ^{3 5 10 11 12}

Eligibility Criteria

This trial is for lymphoma patients, including those with HIV, who have not responded well to previous treatments. They must be in good physical condition (Karnofsky/Lansky score ≥80%), without severe liver disease or serious organ dysfunction. Eligible participants include those with various types of lymphoma such as Mature T-Cell and Mantle Cell Lymphoma after certain responses to therapy, and specific criteria are set for Hodgkin's Lymphoma stages and treatment responses.

Inclusion Criteria

My Lymphoblastic Lymphoma is in second or later complete remission or in first or later partial remission.

I have Mature T-Cell Lymphoma and have undergone initial therapy.

I have Hodgkin Lymphoma and my previous treatments didn't work.

Exclusion Criteria

Pregnant or breastfeeding females

Patients eligible for any higher priority transplant protocols

My cancer did not respond to chemotherapy.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive autologous stem cell transplant with either BEAM, CBV, or CY/TBI regimens

4-6 weeks

Engraftment

Monitoring for platelet and neutrophil engraftment

Up to engraftment

Follow-up

Participants are monitored for progression-free survival, overall survival, and secondary malignancies

3 years

Treatment Details

Interventions

• BCNU (Chemotherapy)
• Cyclophosphamide (Chemotherapy)
• Melphalan (Chemotherapy)
• Peripheral blood stem cell transplantation (Other)
• Total Body Irradiation (Radiation Therapy)

Trial Overview The study tests autologous stem cell transplantation combined with chemotherapy drugs like Etoposide, AraC, G-CSF, Cyclophosphamide, BCNU, Melphalan and procedures like Total Body Irradiation on patients with Hodgkin's and non-Hodgkin's lymphomas. It aims to see how effective this approach is for those who haven't had success with other treatments.

Participant Groups

Group I: CY/TBI Experimental Treatment 4 Interventions

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 II: CBV: HL Experimental Treatment 3 Interventions

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

Group III: BEAM: NHL & HL Experimental Treatment 6 Interventions

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

BCNU is already approved in United States, European Union, Canada for the following indications:

🇺🇸 Approved in United States as Carmustine for:

• Brain tumors
• Hodgkin's disease
• Non-Hodgkin's lymphoma
• Multiple myeloma

🇪🇺 Approved in European Union as Carmustine for:

• Brain tumors
• Hodgkin's disease
• Non-Hodgkin's lymphoma
• Multiple myeloma

🇨🇦 Approved in Canada as Carmustine for:

• Brain tumors
• Hodgkin's disease
• Non-Hodgkin's lymphoma
• Multiple myeloma

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Masonic Cancer Center, University of Minnesota Minneapolis, MN

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota Lead Sponsor

References

1. England pubmed.ncbi.nlm.nih.gov

The Stanford experience with high-dose etoposide cytoreductive regimens and autologous bone marrow transplantation in Hodgkin's disease and non-Hodgkin's lymphoma: preliminary data. [2020] Seventy-seven Hodgkin's disease and non-Hodgkin's lymphoma (NHL) patients received high-dose etoposide in combination with cyclophosphamide and either fractionated total body irradiation (TBI) (n = 28) or carmustine (n = 49) prior to autologous bone marrow transplantation. Marrow from NHL patients was purged in vitro with a panel of monoclonal B- and T-cell antibodies and complement. Six toxic deaths (8%) occurred, all in patients who received carmustine. With a median follow-up of 1 year, 57 patients are alive and free from progressive disease. The 1-year actuarial survival and freedom from progression are 85 and 73% in fractionated TBI/etoposide/cyclophosphamide-treated patients and 79 and 72% in carmustine/etoposide/cyclophosphamide-treated patients. Forty-five of these patients participated in prospective trials for which eligibility criteria were (1) less than 25% curability with conventional therapy; (2) achievement of minimal disease state with conventional therapy; and (3) transplantation early in the course of disease. One-year actuarial survival for 18 patients with relapsed Hodgkin's disease is 80% and for 21 relapsed intermediate and high-grade NHL patients, 70%. One NHL Burkitt's patient was transplanted on a protocol for high-risk intermediate and high-grade NHL in first remission. Five patients with follicular mixed or small cleaved NHL were also transplanted in first remission.

2. United States pubmed.ncbi.nlm.nih.gov

Differences in transplant-related complications between hematologic malignancies and solid tumors receiving high-dose chemotherapy and autologous peripheral blood stem cell transplantation. [2022] Multiple factors contribute to transplant-related complications after high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation, including conditioning regimens, number of infused stem cells and clinical characteristics of patient at transplant. We compared the transplant-related complications of 141 patients affected with hematological malignancies with those of 109 patients with solid tumors. The total number of peripheral blood stem cell transplantations performed was 339. High-dose chemotherapy mainly consisted of melphalan-, busulphan- or thiotepa-based regimens. Despite the equal number of infused CD34+ cells, patients with a hematological malignancy showed a slower absolute neutrophil count (days to neutrophils > 0.5 x 10(9)/L, 10.6 +/- 3.6 for hematological malignancies versus 9.1 +/- 1.2 for solid tumors, P 20 x 10(9)/L, 16.4 +/- 9.8 for hematological malignancies versus 12.3 +/- 4.1 for solid tumors, P

3. Saudi Arabia pubmed.ncbi.nlm.nih.gov

Comparison of Mitoxantrone-Melphalan and BEAM Conditioning Regimens in Patients with Lymphoma. [2023] Lymphoma is seen as a highly treatable and curable malignancy with aggressive treatment methods. Efficacy is often limited by toxicity and many patients need alternative treatment strategies as they cannot tolerate existing high cytotoxic approaches. Our aim is to compare BEAM [carmustine (BCNU), etoposide, cytarabine (ARA-C, cytosine arabinoside), and melphalan] and mitoxantrone-melphalan (Mx-Mel) regimens utilized in our patients with a diagnosis of lymphoma who underwent autologous stem cell transplantation (ASCT), and to demonstrate that the Mx-Mel regimen has similar but less toxic results than the BEAM regimen we have been using frequently as standard conditioning regimen.

4. United States pubmed.ncbi.nlm.nih.gov

Cyclophosphamide, carmustine, and etoposide with autologous bone marrow transplantation in refractory Hodgkin's disease and non-Hodgkin's lymphoma: a dose-finding study. [2017] Cyclophosphamide, carmustine (BCNU), and etoposide (VP-16) (CBV) is a widely used conditioning regimen in autologous bone marrow transplantation (ABMT) of patients with refractory and relapsed lymphoma. However, the maximum-tolerated dose (MTD) of these agents when used in combination has not been systematically explored. We treated 58 patients (28 with non-Hodgkin's lymphoma [NHL], 30 with Hodgkin's disease [HD]) at seven dose levels of CBV. Doses were cyclophosphamide 4,500 to 7,200 mg/m2, BCNU 450 to 600 g/m2, and VP-16 1,200 to 2,000 mg/m2. The MTD was cyclophosphamide 7,200 mg/m2, BCNU 450 mg/m2, and VP-16 2,000 mg/m2. Six hundred milligrams per square meter of BCNU was associated with five of 18 cases of interstitial pneumonitis versus two of 40 at 450 mg/m2 (P = .02). Treatment-related mortality was 5% at dose levels less than or equal to the MTD and 22% at the highest dose. In this heavily pretreated patient population, most of whom had high volume residual disease, complete responses (CRs) to CBV and ABMT occurred in 25% of assessable patients with NHL and 43% of patients with HD. Thirteen of 28 patients with NHL and 14 of 30 with HD remain free from disease progression with median follow-up of 212 and 215 days, respectively. CBV can be administered with acceptable toxicity over a wide range of doses to patients with refractory and relapsed lymphoma.

5. United States pubmed.ncbi.nlm.nih.gov

BEAM-Modified Conditioning Therapy with Cisplatin+Dexamethasone Instead of Carmustine Prior to Autologous Hematopoietic Stem Cell Transplantation (HSCT) in Patients with Hodgkin and Non-Hodgkin Lymphoma. [2020] BACKGROUND High-dose chemotherapy followed by autologous hematopoietic stem cell transplant has proven useful in relapsed or refractory cases of Hodgkin and non-Hodgkin lymphoma. BEAM (carmustine, etoposide, cytarabine, melphalan) is frequently used as a conditioning regimen; however, the high cost and limited availability of BCNU hinders its use in Mexico. MATERIAL AND METHODS Between January 2013 and February 2019, refractory or relapsing HL and NHL patients were treated with an autologous HSCT conditioned with cisplatin+dexamethasone as substitution for BCNU in BEAM. RESULTS Four HL patients and 6 NHL patients were included; 60% were male, the average age was 34.5±15.2 years, the median follow-up was 19.1 months, and 70% had a complete response after transplant. OS at 12 months was 63% for NHL and 100% for HL. Time to hematological recovery was 17.6±2.8 days; all patients developed grade III/IV neutropenia and thrombocytopenia, and 8 patients had transplant-related infections. CONCLUSIONS This retrospective study based on real-world data introduces the option of substituting carmustine with cisplatin+dexamethasone, with a similar response, expected lower cost, and better accessibility in developing nations.

6. India pubmed.ncbi.nlm.nih.gov

A Retrospective Comparison of Mitoxantrone-Melphalan and BEAM Conditioning Regimens Before Autologous Hematopoietic Stem Cell Transplantation in Relapsed/Refractory Lymphoma Patients. [2023] High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (AHSCT) is considered the standard therapy for patients with relapsed lymphoma. The aim of our study is the comparison of mitoxantrone-melphalan and BEAM (carmustine, etoposide, cytarabin and melphalan) conditioning regimens before autologous hematopoietic stem cell transplant in patients with lymphoma. This study has been performed in a retrospective manner. Hundred and two patients with relapsed/refractory Hodgkin lymphoma (n = 35) and non-Hodgkin lymphoma (n = 67) who underwent high-dose treatment followed by AHSCT at Memorial Sisli Hospital between 2013 and 2018 were evaluated. We retrieved data on patient demographics, disease status and post AHSCT outcomes. For conditioning regimen 52 patients received mitoxantrone (60 mg/m2 × 1 day) and melphalan (180 mg/m2 × 1 day) and 50 patients received BEAM (carmustine at 300 mg/m2 × 1 day, etoposide at 200 mg/m2 × 4 days, cytarabine at 2 × 200 mg/m2 × 4 days and melphalan at 140 mg/m2 × 1 day). The median age was 45 (18-73) years at the time of the diagnosis. No significant difference was observed in baseline characteristics between groups, including the disease control and previous therapies. Prior to high-dose chemotherapy, 79.4% of the patients were in complete remission (CR) and 20.6% was in partial remission (PR). With a median follow up of 30.5 months (range: 1-70 months) for the whole cohort, even though the OS was similar in both groups (86% ± 2.4 vs. 84% ± 3.2; p = 0.85), the PFS was noted to be superior among those who received conditioning with BEAM protocol (55% ± 3.7) compared to those with mitoxantrone-melphalan (30.6% ± 2.8; p = 0.006). In conclusion, we demonstrated that the BEAM regimen is an effective high-dose chemotherapy for lymphoma patients before AHSCT. Nevertheless mitoxantrone-melphalan regimen is also an alternative to the BEAM regimen.

7. United States pubmed.ncbi.nlm.nih.gov

A Phase IIb, Multicenter, Open-Label, Safety, and Efficacy Study of High-Dose, Propylene Glycol-Free Melphalan Hydrochloride for Injection (EVOMELA) for Myeloablative Conditioning in Multiple Myeloma Patients Undergoing Autologous Transplantation. [2017] Autologous stem cell transplantation (ASCT) after high-dose melphalan conditioning is considered a standard of care procedure for patients with multiple myeloma (MM). Current formulations of melphalan (eg, Alkeran for Injection [melphalan hydrochloride]; GlaxoSmithKline, Research Triangle Park, NC, USA) have marginal solubility and limited chemical stability upon reconstitution. Alkeran requires the use of propylene glycol as a co-solvent, which itself has been reported to cause such complications as metabolic/renal dysfunction and arrhythmias. EVOMELA (propylene glycol-free melphalan HCl; Spectrum Pharmaceuticals, Inc., Irvine, CA, USA) is a new i.v. melphalan formulation that incorporates Captisol (Ligand Pharmaceuticals, Inc., La Jolla, CA, USA), a specially modified cyclodextrin that improves the solubility and stability of melphalan and eliminates the need for propylene glycol. This new formulation has been shown to be bioequivalent to Alkeran. EVOMELA (200 mg/m(2)) was administered as 2 doses of 100 mg/m(2) each in a phase IIb, open-label, multicenter study to confirm its safety and efficacy as a high-dose conditioning regimen for patients with MM undergoing ASCT. At 5 centers, 61 patients (26 women) with a median age of 62 years (range, 32-73) were enrolled. All patients achieved myeloablation with a median time of 5 days post-ASCT, and all successfully achieved neutrophil and platelet engraftment with median times of 12 days post-ASCT and 13 days post-ASCT, respectively; treatment-related mortality on day 100 was 0%. Overall response rate (according to independent, blinded review) was high (100%), with an overall complete response rate of 21% (13% stringent complete response; 8% complete response) and overall partial response rate of 79% (61% very good partial response; 18% partial response). The incidence of grade 3 mucositis and stomatitis was low (10% and 5%, respectively) with no grade 4 mucositis or stomatitis reported (graded according to National Cancer Institute Common Terminology Criteria for Adverse Events). Based on investigators' assessment of mucositis using the World Health Organization (WHO) oral toxicity scale, 75% of patients had a shift in mucositis score from WHO grade 0 at baseline to a higher grade on study, of which 13% of patients reported WHO grade 3 as the worst post-treatment mucositis over the course of the study; there were no reports of WHO grade 4 mucositis during the study. This study confirms the efficacy and acceptable safety profile of EVOMELA, a new propylene glycol-free melphalan formulation, as a high-dose conditioning regimen for ASCT in patients with MM.

8. United States pubmed.ncbi.nlm.nih.gov

High-dose combination alkylating agents with autologous bone marrow support: a Phase 1 trial. [2017] Twenty-nine patients were treated with 31 courses of high-dose combination cyclophosphamide, cisplatin, and carmustine (BCNU) with and without melphalan with autologous bone marrow support. Toxicity was dose related. The maximum tolerated dose for cyclophosphamide, cisplatin, and BCNU in this combination in mg/m2 was 5,625, 165, and 600, respectively. Further dose escalation was precluded by the development of multiple organ toxicity, including venoocclusive disease, refractory thrombocytopenia, and hypertension. Melphalan added to the three-drug combination produced excessive renal and gastrointestinal toxicity. Objective tumor regression occurred in 21 of 25 evaluable cases. The results suggest that selected alkylating agents can be combined in full or nearly full doses before nonmyelosuppressive dose-limiting toxicity precludes further escalation.

9. England pubmed.ncbi.nlm.nih.gov

Carmustine, Ara C, cyclophosphamide and etoposide with autologous bone marrow transplantation in relapsed or refractory lymphoma: a dose-finding study. [2013] The purpose of this study was to define the dose-limiting non-hematologic toxicity of carmustine, Ara C, cyclophosphamide and etoposide (BACE). Between October 1986 and March 1990, 37 patients with relapsed or refractory lymphoma received escalating doses of combination chemotherapy followed by autologous bone marrow transplant (ABMT). Twenty patients with Hodgkin's disease (HD) and 17 patients with intermediate or high grade non-Hodgkin's lymphoma (NHL) initially received conventional-dose therapy with either a 7 week course of modified MACOP-B or a single dose of cyclophosphamide (CY) at 2 g/m2 depending on prior therapy and response. Regardless of response, patients then received escalating doses of BACE, toxicity permitting. Ten patients obtained complete responses (CR) and 12 patients were partial responders (PR), CR+PR (75%) with modified MACOP-B and 7 (64%) patients obtained PR with CY. The maximum-tolerated dose (MTD) for BACE was determined to be carmustine 700 mg/m2, Ara C 1500 mg/m2, CY 150 mg/kg and etoposide 1500 mg/m2. When Ara C was escalated from 1500 mg/m2 to 3000 mg/m2 holding the other drugs at the prior doses, the next two patients died secondary to diffuse alveolar damage. Overall and event-free survivals are identical with 14 of 37 patients (38%) alive with a median follow-up of 61 months (range 38-79 months). Ten patients were treated at the MTD, none of whom died a toxic death and 3 (30%) are alive with a median follow-up of 42 months (range 38-52 months). We defined the MTD and BACE showing pulmonary toxicity to be the dose-limiting non-hematologic toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

10. United States pubmed.ncbi.nlm.nih.gov

Comparison of autologous bone marrow transplantation with sequential chemotherapy for intermediate-grade and high-grade non-Hodgkin's lymphoma in first complete remission: a study of 464 patients. Groupe d'Etude des Lymphomes de l'Adulte. [2017] Intensive chemotherapy followed by autotransplantation has given promising results in partially responding or sensitive relapsed patients with aggressive non-Hodgkin's lymphoma. In 1987, we designed a randomized study to evaluate the potential benefit of a high-dose regimen containing cyclophosphamide, carmustine, and etoposide (CBV) followed by autotransplantation over a consolidative sequential chemotherapy (ifosfamide, etoposide, asparaginase, and cytarabine) in patients in first complete remission with intermediate- and high-grade non-Hodgkin's lymphoma.

11. England pubmed.ncbi.nlm.nih.gov

Multiple myeloma preparative regimens for high-dose therapy and autologous transplantation: what's new? [2013] High-dose chemotherapy and autologous stem cell transplantation remains a standard procedure in relatively young and selected older patients with multiple myeloma. High-dose melphalan has remained the chemotherapeutic agent of choice based on earlier prospective randomized trials. Despite investigations involving different combinations of chemotherapeutics, radiation and novel agents with and without melphalan, none of these alternative preparative regimens have demonstrated superiority to high-dose melphalan used as a single agent in multiple published studies. In this article, we review the published literature regarding preparative regimens used in patients with multiple myeloma undergoing autologous stem cell transplantation.

12. Turkey pubmed.ncbi.nlm.nih.gov

A Retrospective Comparison of TECAM and BEAM Conditioning Regimens Before Autologous Hematopoietic Stem Cell Transplant in Lymphoma Patients: Efficacy and Toxicity. [2019] The aim of our study was to evaluate the efficacy and toxicity of TECAM (thiotepa, etoposide, cyclophosphamide, cytarabine, and melphalan) and BEAM (carmustine, etoposide, cytarabine, and melphalan) conditioning regimens before autologous hematopoietic stem cell transplant in patients with lymphoma.