Chemotherapy + Stem Cell Transplant for Pancreatic Cancer
Recruiting in Palo Alto (17 mi)
+1 other location
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: General Oncology, Inc.
Must not be taking: Immunosuppressants, CYP2b6 inducers, Disulfiram
Disqualifiers: Cholangitis, Hypertension, Heart disease, others
No Placebo Group
Trial Summary
What is the purpose of this trial?The clinical trial is a phase 1, single-arm trial that will evaluate the safety of the investigational treatment on metastatic cancer in patients who have a deleterious or suspected deleterious BRCA1, BRCA2, or PALB2 genetic alteration. The investigational treatment will involve 2 cycles of a combination of intravenous melphalan, BCNU, low-dose I.V. ethanol, vitamin B12b, and vitamin C in association with autologous hematopoietic stem cell infusion. A dose-escalation schedule will be employed for vitamin C.
Do I need to stop my current medications for the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have chemotherapy within 2 weeks of enrollment, and certain medications like CYP2b6 inducers and disulfiram must be stopped 21 and 30 days before treatment, respectively.
What data supports the effectiveness of the treatment involving chemotherapy and stem cell transplant for pancreatic cancer?
Research shows that high-dose melphalan, used with autologous bone marrow rescue, can be effective in treating tumors resistant to standard chemotherapy, with some patients achieving partial or complete remission. This suggests potential benefits for similar treatments in other cancers, like pancreatic cancer.
12345Is the combination of chemotherapy and stem cell transplant generally safe for humans?
The combination of chemotherapy and stem cell transplant has been studied in various conditions and is generally considered safe, though it can cause significant side effects like mucositis (painful inflammation and ulceration of the mucous membranes lining the digestive tract) and nausea/vomiting. Some studies report a treatment-related mortality rate of around 6.7%, and older patients may experience more severe toxicities. However, with supportive treatments like amifostine, some side effects can be managed, allowing for higher doses of chemotherapy.
678910How does the treatment of chemotherapy and stem cell transplant for pancreatic cancer differ from other treatments?
This treatment combines high-dose chemotherapy with autologous stem cell transplantation, which helps reduce the severe blood-related side effects of chemotherapy by replenishing the body's blood-forming cells. This approach is particularly useful for tumors that are resistant to standard chemotherapy doses, offering a potential option for patients in the early stages of disease who have not undergone extensive prior treatments.
311121314Eligibility Criteria
This trial is for adults with stage IV breast or pancreatic cancer who have a BRCA1, BRCA2, or PALB2 mutation. They should not have had chemotherapy in the last 2 weeks and must be expected to live at least another 6 months. Participants need a Karnofsky score of at least 60%, indicating they can care for themselves. Smokers must quit for the trial duration, and all participants agree to use contraception.Inclusion Criteria
Agreement to contraception for female participants of childbearing potential
Your disease can be measured or seen on medical tests using specific guidelines.
My life expectancy is mainly affected by my cancer, not other diseases.
+13 more
Exclusion Criteria
I had chemotherapy for a different cancer within the last year, with a high risk of it coming back.
I have a serious heart or blood vessel condition.
Abnormal test results from lab tests.
+18 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Stem Cell Mobilization and Collection
Granulocyte colony-stimulating factor and Plerixafor are used to mobilize bone marrow stem cells, which are collected by apheresis.
1-2 weeks
1 visit (in-person)
Treatment Cycle 1
Participants receive the first cycle of investigational drug therapy with stem cell infusion, including melphalan, BCNU, vitamin B12b, vitamin C, and ethanol.
1 week
Daily visits during treatment week
Inter-cycle Interval
Interval between the first and second treatment cycles.
6 weeks
Treatment Cycle 2
Participants receive the second cycle of investigational drug therapy with stem cell infusion.
1 week
Daily visits during treatment week
Follow-up
Participants are monitored for safety and effectiveness after treatment, including assessments for adverse events and progression-free survival.
12 months
Participant Groups
The SHARON trial tests a treatment combining chemotherapy drugs (melphalan, BCNU), vitamins (B12b, C), ethanol, and patients' own stem cells on metastatic cancer with specific genetic mutations. It's in phase 1 where safety is checked using increasing doses of vitamin C alongside other treatments given intravenously over two cycles.
1Treatment groups
Experimental Treatment
Group I: Chemotherapy/stem cell treatmentExperimental Treatment6 Interventions
Autologous Hematopoietic Stem Cells is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Autologous Hematopoietic Stem Cells for:
- Multiple Myeloma
- Non-Hodgkin Lymphoma
- Leukemia
- Lymphoma
- Autoimmune Diseases
🇪🇺 Approved in European Union as Autologous Hematopoietic Stem Cells for:
- Multiple Myeloma
- Non-Hodgkin Lymphoma
- Leukemia
- Lymphoma
- Autoimmune Diseases
🇨🇦 Approved in Canada as Autologous Hematopoietic Stem Cells for:
- Multiple Myeloma
- Non-Hodgkin Lymphoma
- Leukemia
- Lymphoma
- Autoimmune Diseases
🇯🇵 Approved in Japan as Autologous Hematopoietic Stem Cells for:
- Multiple Myeloma
- Non-Hodgkin Lymphoma
- Leukemia
- Lymphoma
- Autoimmune Diseases
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Memorial Sloan Kettering Cancer CenterNew York, NY
Massachusetts General HospitalBoston, MA
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Who Is Running the Clinical Trial?
General Oncology, Inc.Lead Sponsor
Myriad Genetics, Inc.Industry Sponsor
References
Treatment of advanced malignant melanoma with high-dose chemotherapy and autologous bone marrow transplantation. Preliminary results--Phase I study. [2019]Thirteen patients with advanced (Stage III) malignant melanoma have been treated with high-dose chemotherapy (nitrogen mustard or a combination of BCNU and melphalan) combined with autologous, nonfrozen, bone marrow transplantation. Three patients (24%) achieved a complete remission and are currently alive and free of disease without further therapy at 26, 60, and 73 weeks. Five patients (38%) achieved partial remissions and five patients (38%) had no response. There was no difference in the response rate to nitrogen mustard and the BCNU-melphalan combination. Severe side effects to nitrogen mustard, however, precluded its further use in this study. The major cause of death in patients was intracerebral metastases, raising the question of prophylactic brain irradiation in future studies. Studies of the recovery rate of peripheral blood neutrophil, platelet, and peripheral blood and bone marrow CFU-C suggest that autologous bone marrow infusion may be of benefit in shortening hematopoietic recovery following intensive chemotherapy.
Autologous bone marrow transplantation in solid tumors. [2019]Recent studies in autologous bone marrow or peripheral blood transplantation in solid tumors are discussed. The toxicity and activity of high-dose cisplatin or carboplatin combined with etoposide and other drugs are described. The results of trials in nonseminomatous germ cell tumors, neuroblastoma, ovarian cancer, and brain tumors are detailed and discussed. The impressive antitumor activities noted in certain subgroups should lead to an early application of these strategies before drug resistance becomes prevalent.
High dose melphalan with autologous marrow rescue in cancer treatment. [2013]Autologous bone marrow rescue circumvents the major toxicity of most cancer chemotherapeutic agents. Melphalan is a particularly well suited agent for use with autologous bone marrow rescue and produces response in chemo-resistant tumours. Thirteen patients have been treated with high dose melphalan with autologous bone marrow rescue in this department. The aims of treatment were palliation, debulking of non-resectable tumours and curative adjuvant therapy. Three patients died of melphalan related toxicity. Of the remaining ten patients there were five partial remissions, one objective response, one complete remission, one with no response and two patients in whom the response is not yet assessable (adjuvant therapy). In our experience high dose melphalan is an effective means of killing tumour cells which are not sensitive to chemotherapy at conventional doses. It is recommended in young patients who have not had extensive previous radio- or chemotherapy, in the early stages of disease, with cure or prolonged remission the aim. High dose melphalan is not recommended in the older patient or in those with massive diseases and is no longer used with palliative intent.
High dose melphalan and non-cryopreserved autologous bone marrow treatment of malignant melanoma and neuroblastoma. [2013]Autologous non-cryopreserved bone marrow infused 8 hours after an intravenous injection of melphalan, 140 mg/m2, accelerates bone marrow recovery. This effect is most noticeable in the recovery of peripheral blood granulocytes. Twenty patients with disseminated malignant melanoma were treated with this regimen: there were 12 responses, two of them complete but the toxicity of the treatment was not sufficient to justify using this method of treatment routinely since survival was little influenced by treatment (4-11 months). In 8 patients with disseminated neuroblastoma, high dose melphalan/autograft was used in a program of combined modality treatment. Three of the patients are disease free at 16, 11 and 6 months and in one the disease is 'static', not having grown for 13 months. The treatment for this tumour deserves further exploration, and perhaps similar treatment ought to be explored for other tumours.
Intensive melphalan chemotherapy and cryopreserved autologous bone marrow transplantation for the treatment of refractory cancer. [2017]Thirty-three adult and pediatric patients with refractory malignancies were treated with escalating doses of melphalan (120-225 mg/m2 IV over 3 days) followed by reinfusion of previously harvested and cryopreserved autologous marrow. The hematological and nonhematological toxicities and the therapeutic effects of this regimen were evaluated. Increasing doses of melphalan did not alter the rate of decline nor the recovery of peripheral blood counts. Granulocyte (greater than 500/microL) and platelet count (greater than 20,000/microL) recovery occurred in a median of 19 (range 12-54) and 24 (range: 12-54) days after bone marrow transplantation, respectively. Five patients experienced severe infection, three of which were fatal, and one patient died due to thrombocytopenic hemorrhage. Toxicity to the gastrointestinal system was dose limiting. The maximum tolerated dose of melphalan was 180 mg/m2; only three of 24 patients experienced severe stomatitis, esophagitis, and diarrhea at this level or less, while eight of nine patients at 225 mg/m2 were affected (p less than 0.005). Administration of cyclophosphamide (300 mg/m2 IV) 1 week before melphalan therapy did not reduce the incidence of severe gastrointestinal toxicity. Plasma melphalan concentration peaked 30-60 min after infusion (4.8-11.5 micrograms/mL) but declined rapidly. Cerebrospinal fluid concentration was 10% of the corresponding plasma concentration and was undetectable at 3 hours. Antitumor responses occurred in nine of 13 patients with malignant melanoma (five complete and four partial remissions), and ranged 2-12+ months with a median of 5 months. Four of six neuroblastomas demonstrated responses (three complete and one partial remission( lasting a median of 7.5 (range: 5-10) months. Other tumors in which this regimen had activity included breast cancer and Ewing's sarcoma. The overall response rate for the 33 patients was 30% complete remissions (10 patients) and 21% partial remissions (seven patients). High dose melphalan and autologous bone marrow transplantation is a promising therapy for patients with malignancies for which no effective treatment is known or for patients whose cancer is refractory to conventional therapeutic agents.
Hematopoietic stem cell deficit of transplanted bone marrow previously exposed to cytotoxic agents. [2013]High-dose chemotherapy and/or total body irradiation followed by autologous bone marrow rescue has improved the survival of patients with a variety of malignancies. Candidates for autologous bone marrow transplantation (ABMT) often have received prior exposure to cytotoxic agents, some of which may damage primitive stem cells. We have developed an in vivo murine model to evaluate the effects of a number of individual cytotoxic agents on the ability of syngeneic donor marrow to provide long-term hematopoiesis in recipients following high-dose total body irradiation. Marrow was experimentally obtained by giving donor mice 6 weekly injections of saline, cytosine arabinoside, cyclophosphamide, cisplatin, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), or busulfan, drugs known to have differing effects on primitive hematopoietic stem cells. After time to allow recovery of marrow and peripheral blood counts, 1 x 10(7) marrow cells from these mice were transplanted into lethally irradiated syngeneic recipients. Five to 6 months after marrow transplantation, the quality of long-term hematopoietic recovery was measured by WBC counts, marrow cellularity, CFU-S content, and determinations of stem cell self-renewal. Abnormalities were noted with the use of donor marrow exposed to all cytotoxic agents. Recipients of marrow previously exposed to cytosine arabinoside, an agent that spares the most primitive stem cells, were the least affected. Recipients of marrow previously exposed to busulfan, an agent known to damage primitive stem cells, were most affected with a decrease in peripheral blood counts, marrow cellularity, stem cell content, self-renewal capacity, and long-term survival. A decrease in hematopoietic stem cell self-renewal was seen in recipients of marrow previously exposed to cyclophosphamide, cisplatin, and BCNU even when marrow cellularity and CFU-S content were normal. These data suggest that the capacity of syngeneic donor marrow to provide long-term hematopoiesis in lethally irradiated recipients is dependent on its donor marrow primitive stem cell content. Long-term hematopoiesis may be severely compromised in recipients of donor stem cells previously exposed to cytotoxic agents which damage primitive stem cells.
The potential of amifostine in high-dose chemotherapy and autologous hematopoietic stem cell transplantation. [2013]Amifostine treatment may allow chemotherapy dose increases beyond those permitted by autologous hematopoietic stem cell transplantation. In a recent study in patients with solid tumors receiving a high-dose regimen of etoposide, ifosfamide, and carboplatin plus autologous stem cell transplantation, amifostine pretreatment was associated with significant reductions in time to neutrophil and thrombocyte engraftment, fewer days of neutropenic fever, less need for salvage antibiotic therapy. Also, there were significant reductions in grade 3 or 4 stomatitis/diarrhea, and delayed nausea/vomiting. A phase I/II study in patients with refractory/high-risk malignancies indicated that a 140% increase of high-dose melphalan (up to 280 mg/m2) can be safely used with amifostine and autologous stem cell transplantation with manageable mucosal toxicity and a reduced incidence of regimen-related toxicity. Preliminary findings in another phase II study indicate that melphalan 280 mg/m2 can also be safely used with amifostine/stem cell transplantation in the treatment of patients with myeloma. Additional studies are ongoing or planned to examine the potential hematoprotective and hematostimulating effects of amifostine in the setting of high-dose chemotherapy and autologous stem cell transplantation.
Toxicities of high-dose chemotherapy and autologous hematopoietic cell transplantation in older patients with lymphoma. [2021]High-dose chemotherapy and autologous hematopoietic cell transplantation is an effective consolidation therapy in lymphoma; however, its use in elderly patients has been limited because of concerns for greater toxicity in this group. We investigated the toxicities of carmustine, etoposide, cytarabine, and melphalan (BEAM) and autologous hematopoietic cell transplantation (AHCT) in 346 patients in 2 age groups: 279 patients aged 60 to 69 years and 67 patients aged ≥70 years. The majority developed severe toxicities; the most common were febrile neutropenia, gastrointestinal, infections, and cardiovascular. Older patients were at higher risk for grade ≥3 cardiovascular toxicities (hazard ratio [HR], 3.36; 95% confidence interval [CI], 2.25-5.00; P
An expanded phase I/II trial of cyclophosphamide, etoposide, and carboplatin plus total body irradiation with autologous marrow or stem cell support for patients with hematologic malignancies. [2019]The major cause for failure of autologous stem cell transplantation for hematologic malignancies is the risk of recurrent disease. As a result, new treatment regimens that include novel agents or combinations of agents and approaches are needed. The current report describes a large Phase I/II, single-center trial that includes 60 patients with a variety of hematologic malignancies. These patients received a fixed dose of carboplatin (1 g/m(2)/d x 72 hours by CI) etoposide (600 mg/m(2)/d x 3 days) and cyclophosphamide (2 g/m(2)/d x 3 days), plus escalating doses of total body irradiation (TBI) (at 1000, 1200, and 1295 cGy) over 3 days. Eleven patients received infusion of autologous marrow, 32 received peripheral blood stem cells, and 17 patients received both. The maximum tolerated dose of this regimen was a radiation dose of 1200 cGy given in 200-cGy fractions BID x 3 days. The dose-limiting toxicity was mucositis, with 97% of patients requiring narcotic analgesia for mouth pain. Overall treatment-related mortality was 6.7%, with 2 of the 4 deaths occurring in a group of 9 patients aged 60 and older. Responses were seen in all patient groups, but the most encouraging outcomes were seen in 12 patients with high-risk or advanced acute myelocytic lymphoma (AML), 7 of whom remain alive and free of disease beyond 5 years. This regimen is intensive and causes considerable mucositis but is otherwise well tolerated and has demonstrated activity in a number of hematologic malignancies, especially AML.
High-dose chemotherapy with autologous bone marrow support in advanced malignant melanoma. [2018]Eight patients with advanced malignant melanoma were treated with high-dose melphalan (80-90 mg/m2) and BCNU (600-800 mg/m2). In all patients autologous bone marrow preservation was performed prior to therapy. Bone marrow was stored for 48 h in a refrigerator at 10 degrees C and reinfused 48 h post-therapy. Three patients had a complete response (CR), 1 a partial response and 4 patients no response. Two patients with CR died 4 and 5 months after therapy. One had an interstitial pneumonitis and 1 patient died from unknown cause. The third patient had a relapse 12 months after therapy. Major side effects were severe nausea/vomiting and a mild mucositis. Two patients suffered from BCNU-related encephalopathy. All patients had a full hematologic reconstitution after 6 weeks. High-dose chemotherapy with autologous bone marrow support achieves a high response rate. Long-term disease-free survival, however, was not seen with this approach.
[Peripheral stem cells: from biology to therapy]. [2007]The tumor cells' response to more aggressive treatment has been shown in many different malignancies with various drugs, as alkylating agents, antimetabolites and anthracyclines. The use of high-dose chemotherapy is limited by especially haematological toxicity. Autologous stem cell transplantation (ASCT) is now used to prevent or decrease haematological toxicity induced by intensive chemotherapy. Stem cells can be harvested using bone marrow or peripheral blood. In both cases recombinant human growth factors (G-CSF, GM-CSF, IL3) have been administrated to decrease marrow aplasia duration after transplant. Peripheral blood stem cell autograft seems to be the first transplantation technique in patients with bone marrow hypocellularity induced by previous irradiation and/or neoplastic involvement.
Feasibility and toxicity study of a high-dose chemotherapy regimen for autotransplantation incorporating carboplatin, cyclophosphamide and thiotepa. [2020]Sixteen patients received a high-dose chemotherapy regimen consisting of carboplatin (1600 mg/m2) and cyclophosphamide (6000 mg/m2) as daily two-hour infusions over four days (CC). All but two of them also received thiotepa (480 mg/m2) in eight 30-minute infusions given every 12 hours (CTC). Bone marrow and/or peripheral stem cell (PSC) reinfusions took place 72 hours after the last course of chemotherapy. The major toxicity was bone marrow suppression, the duration of which was markedly reduced in the patients receiving PSC reinfusions. Non-hematological toxicity was relatively mild and consisted of nausea and vomiting, minor mucositis and skin rashes. All but one patient had mild and completely reversible elevations of serum ALAT and/or LDH levels. One patient, who had received full-dose chemotherapy despite a creatinine clearance of 56 ml/min, developed significant toxicity consisting of transient cyclophosphamide-associated pancarditis, reversible neurotoxicity and partially reversible hearing loss and renal function impairment. There were no toxic deaths. In view of the high carboplatin dose, the CTC regimen may be particularly suitable for use in the salvage treatment of germ cell cancer. Since CTC causes no serious organ toxicity, further studies to determine its suitability for double or even triple transplantation programs are warranted.
High-dose gemcitabine, busulfan, and melphalan for autologous stem-cell transplant in patients with relapsed or refractory myeloma: a phase 2 trial and matched-pair comparison with melphalan. [2022]High-dose melphalan is of little benefit as a regimen for patients with relapsed or refractory myeloma undergoing an autologous stem-cell transplant (ASCT). The poor performance of single-agent melphalan in this setting prompted us to study a new high-dose combination of infused gemcitabine, busulfan, and melphalan.
Phase II trial of intravenous melphalan in advanced colorectal carcinoma. [2019]Relatively few studies have examined the activity of alkylating agents in the treatment of advanced colorectal adenocarcinoma. Recent reports have suggested possible therapeutic activity for high-dose intravenous melphalan administered with autologous bone marrow transplantation (BMT) support. We conducted a phase II study to determine the efficacy of administering intravenous melphalan at doses that do not require BMT support in patients with advanced colorectal adenocarcinoma.