CLINICAL TRIALS PROFILE FOR OFORTA

All Clinical Trials for Oforta

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00104858 ↗	Fludarabine Phosphate, Radiation Therapy, and Rituximab in Treating Patients Who Are Undergoing Donor Stem Cell Transplant Followed by Rituximab for High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma	Completed	National Cancer Institute (NCI)	Phase 2	2004-12-01	This phase II trial studies how well fludarabine phosphate with radiation therapy and rituximab followed by donor stem cell infusions work in treating patients with high-risk chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with low side effects. Nonmyeloablative stem cell transplants use low doses of chemotherapy (fludarabine phosphate) and radiation to suppress the patient's immune system enough to prevent rejection of the donor's stem cells. Following infusion of donor stem cells, a mixture of the patient's and the donor's stem cells will exist and is called "mixed chimerism". Donor cells will attack the patient's leukemia. This is called the "graft-versus-leukemia" effect. Rituximab will be given 3 days before and three times after infusing stem cells to help in controlling CLL early after transplant till the "graft-versus-leukemia" takes control. Further, rituximab could augment the "graft-versus-leukemia" effect by activating donor immune cells and hence improve disease control. Sometimes the transplanted cells from a donor can also attack the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
NCT00104858 ↗	Fludarabine Phosphate, Radiation Therapy, and Rituximab in Treating Patients Who Are Undergoing Donor Stem Cell Transplant Followed by Rituximab for High-Risk Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma	Completed	Fred Hutchinson Cancer Research Center	Phase 2	2004-12-01	This phase II trial studies how well fludarabine phosphate with radiation therapy and rituximab followed by donor stem cell infusions work in treating patients with high-risk chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with low side effects. Nonmyeloablative stem cell transplants use low doses of chemotherapy (fludarabine phosphate) and radiation to suppress the patient's immune system enough to prevent rejection of the donor's stem cells. Following infusion of donor stem cells, a mixture of the patient's and the donor's stem cells will exist and is called "mixed chimerism". Donor cells will attack the patient's leukemia. This is called the "graft-versus-leukemia" effect. Rituximab will be given 3 days before and three times after infusing stem cells to help in controlling CLL early after transplant till the "graft-versus-leukemia" takes control. Further, rituximab could augment the "graft-versus-leukemia" effect by activating donor immune cells and hence improve disease control. Sometimes the transplanted cells from a donor can also attack the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
NCT00060424 ↗	Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia	Completed	National Cancer Institute (NCI)	Phase 2	2003-03-01	This clinical trial studies how well giving fludarabine phosphate together with total-body irradiation (TBI) before donor peripheral blood stem cell transplant works in treating patients with chronic lymphocytic leukemia or small lymphocytic leukemia. Giving low doses of chemotherapy, such as fludarabine phosphate, and TBI before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. Giving chemotherapy before or after peripheral blood stem cell transplant also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before and after the transplant may stop this from happening.
NCT00060424 ↗	Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia	Completed	Fred Hutchinson Cancer Research Center	Phase 2	2003-03-01	This clinical trial studies how well giving fludarabine phosphate together with total-body irradiation (TBI) before donor peripheral blood stem cell transplant works in treating patients with chronic lymphocytic leukemia or small lymphocytic leukemia. Giving low doses of chemotherapy, such as fludarabine phosphate, and TBI before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. Giving chemotherapy before or after peripheral blood stem cell transplant also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil before and after the transplant may stop this from happening.
NCT00034528 ↗	Stem Cell Transplantation After Reduced-Dose Chemotherapy for Patients With Sickle Cell Disease or Thalassemia	Terminated	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 2	2001-09-01	The purpose of this study is to find out if using a lower dose of chemotherapy before stem cell transplantation can cure patients of sickle cell anemia or thalassemia while causing fewer severe side effects than conventional high dose chemotherapy with transplantation.
NCT00005803 ↗	Autologous Stem Cell Transplant Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoma	Completed	National Cancer Institute (NCI)	Phase 1/Phase 2	1999-09-01	This phase I/II trial studies how well autologous stem cell transplant followed by donor stem cell transplant works in treating patients with lymphoma that has returned or does not respond to treatment. Peripheral blood stem cell transplant using stem cells from the patient or a donor may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells. The donated stem cells may also help destroy any remaining cancer cells (graft-versus-tumor effect).
NCT00005803 ↗	Autologous Stem Cell Transplant Followed by Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoma	Completed	Fred Hutchinson Cancer Research Center	Phase 1/Phase 2	1999-09-01	This phase I/II trial studies how well autologous stem cell transplant followed by donor stem cell transplant works in treating patients with lymphoma that has returned or does not respond to treatment. Peripheral blood stem cell transplant using stem cells from the patient or a donor may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells. The donated stem cells may also help destroy any remaining cancer cells (graft-versus-tumor effect).

Clinical Trial Conditions for Oforta

Condition Name

Condition Name for Oforta
Intervention	Trials
Refractory Chronic Lymphocytic Leukemia	4
Recurrent Small Lymphocytic Lymphoma	4
Previously Treated Myelodysplastic Syndrome	3
Recurrent Chronic Lymphocytic Leukemia	3

Condition MeSH

Condition MeSH for Oforta
Intervention	Trials
Leukemia	9
Leukemia, Myeloid, Acute	7
Leukemia, Lymphoid	6
Leukemia, Myeloid	6

Clinical Trial Locations for Oforta

Trials by Country

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−

Trials by Country for Oforta
Location	Trials
United States	51
Canada	4
Australia	4
Italy	2
Denmark	1

Trials by US State

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−

Trials by US State for Oforta
Location	Trials
Washington	10
California	8
Wisconsin	5
Tennessee	3
Minnesota	3

Clinical Trial Progress for Oforta

Clinical Trial Phase

Clinical Trial Phase for Oforta
Clinical Trial Phase	Trials
Phase 2	8
Phase 1/Phase 2	2
Phase 1	8

Clinical Trial Status

Clinical Trial Status for Oforta
Clinical Trial Phase	Trials
Completed	10
Recruiting	3
Terminated	3

Clinical Trial Sponsors for Oforta

Sponsor Name

Sponsor Name for Oforta
Sponsor	Trials
National Cancer Institute (NCI)	15
Fred Hutchinson Cancer Research Center	9
City of Hope Medical Center	3

Sponsor Type

Sponsor Type for Oforta
Sponsor	Trials
Other	25
NIH	21
Industry	3

OFORTA (Fludarabine Phosphate) Tablets: A Comprehensive Update

Introduction

OFORTA, also known as fludarabine phosphate, is a medication that was approved for the treatment of adult patients with B-cell chronic lymphocytic leukemia (CLL) who had not responded to or had progressed during or after treatment with at least one standard alkylating-agent containing regimen. Here, we will delve into the clinical trials, market analysis, and projections for this drug.

Clinical Trials and Approval History

OFORTA was approved by the FDA on December 18, 2008, under the accelerated approval program, which allows for the approval of drugs based on surrogate endpoints that are reasonably likely to predict clinical benefit, with the condition that the manufacturer conducts postmarketing studies to verify clinical benefit[2].

The drug was studied in two clinical trials involving patients with CLL. Study 1 included 78 patients who had received prior therapy, and Study 2 included 81 patients who had not received prior therapy. These trials provided the initial data for its approval, although they did not directly compare the clinical efficacy and safety of oral fludarabine phosphate to its intravenous form[1].

Postmarketing Study and Withdrawal

Despite the initial approval, the postmarketing study required to verify the clinical benefit of OFORTA was never completed. Sanofi-aventis, the manufacturer, faced significant challenges in recruiting subjects and cited lack of commercial demand as reasons for not completing the study. As a result, the FDA requested the voluntary withdrawal of OFORTA from the market, which was officially withdrawn on December 31, 2011[2][4].

Adverse Reactions and Safety Profile

During the clinical trials, OFORTA was associated with various adverse reactions. The data from 159 patients exposed to the drug showed a range of side effects, although the adverse reaction rates observed in these trials cannot be directly compared to those of other drugs due to varying conditions[1].

Market Analysis

The withdrawal of OFORTA from the market highlights the complexities and risks associated with accelerated approvals. Despite its initial promise, the drug failed to meet the postapproval requirements, leading to its removal.

The global clinical trials market, however, continues to grow, driven by the increasing demand for treatments for chronic diseases. The market is projected to grow from $61.58 billion in 2024 to $106.78 billion by 2032, at a CAGR of 7.1%[3].

Impact on CLL Treatment Landscape

The withdrawal of OFORTA does not significantly impact the overall CLL treatment landscape, as other treatments remain available. However, it underscores the importance of completing postmarketing studies to ensure the long-term efficacy and safety of drugs.

Lessons from Accelerated Approval Program

The case of OFORTA serves as an example of the challenges and risks associated with the FDA's accelerated approval program. While this program can expedite the availability of potentially life-saving treatments, it also requires rigorous postmarketing studies to confirm clinical benefit. The failure to complete these studies can lead to the withdrawal of the drug, as seen with OFORTA and other drugs like durvalumab and pembrolizumab in certain indications[4].

Market Projections and Future Outlook

Given the withdrawal of OFORTA, there are no current market projections for this specific drug. However, the broader market for CLL treatments continues to evolve with new therapies and ongoing clinical trials.

Global CLL Treatment Market

The global market for CLL treatments is part of the larger oncology market, which is driven by advancements in targeted therapies and immunotherapies. As new treatments emerge and existing ones are refined, the market is expected to grow, albeit without the contribution of OFORTA.

Key Takeaways

• Approval and Withdrawal: OFORTA was approved under the FDA's accelerated approval program but was withdrawn due to the lack of completion of postmarketing studies.
• Clinical Trials: The drug was studied in two clinical trials, but no direct comparison was made to its intravenous form.
• Market Impact: The withdrawal of OFORTA does not significantly impact the CLL treatment landscape but highlights the importance of postmarketing studies.
• Future Outlook: The global CLL treatment market continues to grow with new therapies and ongoing clinical trials.

FAQs

What was OFORTA used for?

OFORTA (fludarabine phosphate) was used for the treatment of adult patients with B-cell chronic lymphocytic leukemia (CLL) whose disease had not responded to or had progressed during or after treatment with at least one standard alkylating-agent containing regimen.

Why was OFORTA withdrawn from the market?

OFORTA was withdrawn from the market because the postmarketing study required to verify its clinical benefit was not completed, and there was a lack of commercial demand.

What are the common adverse reactions associated with OFORTA?

The adverse reactions associated with OFORTA include a range of side effects observed in clinical trials, although the exact rates cannot be directly compared to other drugs due to varying conditions.

How does the withdrawal of OFORTA affect the CLL treatment landscape?

The withdrawal of OFORTA does not significantly impact the CLL treatment landscape, as other treatments remain available.

What is the current market outlook for CLL treatments?

The global market for CLL treatments is expected to grow as new therapies and ongoing clinical trials continue to evolve the treatment options available.

Sources

1. Sanofi US. OFORTA™ (fludarabine phosphate) Tablets - Sanofi US.
2. Federal Register. Withdrawal of Approval of a New Drug Application for OFORTA.
3. Fortune Business Insights. Clinical Trials Market SIZE, SHARE | GROWTH REPORT [2032].
4. HOPA News. The FDA Accelerated Approval Program: A Double Edged Sword.
5. JAMA Health Forum. The Perils of Increasing Medicaid Rebates for Drugs With Accelerated Approval.