Palifermin + Leuprolide Acetate for Hematopoietic Stem Cell Transplantation in Blood Cancers

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Active infection, Prior transplant, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

82 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to help determine if palifermin and leuprolide acetate can help the immune system recover faster following a stem cell transplant. Blood stem cells are very young blood cells that grow in the body to become red or white blood cells or platelets. The transplant uses stem cells in the blood from another person. The donor can be a family member or a volunteer donor. This is called an allogeneic stem cell transplant. The investigators want to see if palifermin and leuprolide acetate can help the immune system recover faster after an allogenic transplant because experiments have shown they may be able to do this.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Palifermin + Leuprolide Acetate for hematopoietic stem cell transplantation in blood cancers?

Research shows that leuprolide, a component of the treatment, helps improve blood cell recovery after chemotherapy in leukemia patients by increasing platelet and lymphocyte counts. Additionally, leuprolide is effective in preventing uterine bleeding in women undergoing stem cell transplantation, which suggests it has a beneficial role in managing side effects during such procedures. ^{1 2 3 4 5}

Is the combination of Palifermin and Leuprolide Acetate safe for use in humans?

Leuprolide Acetate has been used safely in premenopausal women undergoing stem cell transplantation to prevent menstrual bleeding, with no observed side effects. It has an excellent safety profile and does not interfere with blood clotting or liver function. ^{1 2 3 6 7}

How is the drug Palifermin + Leuprolide Acetate unique for blood cancer stem cell transplantation?

This drug combination is unique because it uses Palifermin to protect and repair the mouth and throat lining during chemotherapy, while Leuprolide Acetate helps improve blood cell recovery by blocking certain hormones. This dual approach aims to enhance recovery and reduce complications during stem cell transplantation. ^{2 3 4 6 8}

Research Team

Miguel Angel Perales, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults aged 18-60 with certain blood cancers like leukemia, lymphoma, or myelodysplastic syndrome who are in remission but at high risk for relapse. They must be fit enough for a stem cell transplant (with performance status ≥70%) and have good organ function. Pregnant women, recent transplant recipients, those with active infections or HIV are excluded.

Inclusion Criteria

My condition is chronic myelomonocytic leukemia, either CMML-1 or CMML-2.

My AML is in its second or later remission.

My leukemia is in its first remission but at high risk of returning, or it's in a second or later remission.

Exclusion Criteria

I am HIV positive.

Pregnant or breast feeding

Patient is felt to not be a candidate for TBI by the BMT service

Timeline

Screening

Participants are screened for eligibility to participate in the trial

3-6 weeks

1 visit (in-person)

Pre-transplant Conditioning

Participants receive Lupron or Degarelix and undergo total body irradiation, thiotepa, cyclophosphamide, and anti-thymocyte globulin administration

9 days

Daily visits for treatment administration

Transplantation

Participants undergo T-cell depleted allogeneic hematopoietic stem cell transplant

1 day

1 visit (in-person)

Post-transplant Treatment

Participants receive additional doses of palifermin and Lupron or Degarelix

3 months

Regular follow-up visits

Follow-up

Participants are monitored for immune recovery, overall survival, and incidence of infections

2 years

Regular follow-up visits

Treatment Details

Interventions

• Lupron
• Palifermin

Trial Overview The trial is testing if palifermin combined with leuprolide acetate can speed up immune recovery after an allogeneic stem cell transplant following total body irradiation. Participants will receive these drugs along with standard treatments including chemotherapy and radiation.

Participant Groups

Group I: palifermin with Lupron Experimental Treatment 6 Interventions

All patients undergo total body irradiation (TBI) on days -9 to -6 \& receive thiotepa intravenously (IV) over 2-4 hours on days -5 to -4, cyclophosphamide IV over 30-60 minutes on days -3 to -2, \& anti-thymocyte globulin infused over 12 hours on days -3 to -2 Pts undergo T-cell depleted allogeneic hematopoietic stem cell transplant on day 0. Pts will receive a three month depot dose of Lupron 3-6 weeks prior to the start date of the pre-transplant conditioning regimen. Pts will receive palifermin at 60mcg/kg/day IV on three consecutive days, 24 hours apart with the last dose administered no less than 24 \& no more than 48 hours prior to the start of cytoreduction. Pts will receive three additional daily doses of palifermin the first approximately 6 hours after the stem cell infusion on day 0, followed by two daily doses given at 24 hour intervals on d+1 \& d+2. Pts will receive a further 3-month depot injection of Lupron approximately 3 months (+/- one week) post the first dose.

Group II: palifermin with Degarelix Experimental Treatment 6 Interventions

Participants on the degarelix arm will receive a loading dose of degarelix 240 mcg subcutaneous 4-14 days before the start of pre-transplant conditioning. All participants will receive palifermin at 60mcg/kg/day IV on three consecutive days, 24 hours apart with the last dose administered no less than 24 and no more than 48 hours prior to the start of cytoreduction.

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Swedish Orphan Biovitrum

Industry Sponsor

Trials

103

Recruited

13,300+

Dr. Guido Oelkers

Swedish Orphan Biovitrum

Chief Executive Officer since 2017

PhD in Economics

Dr. Lydia Abad-Franch

Swedish Orphan Biovitrum

Chief Medical Officer since 2023

MD, MBA

References

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

Ovarian function after hematopoietic cell transplantation: a descriptive study following the use of GnRH agonists for myeloablative conditioning and observation only for reduced-intensity conditioning. [2018]

2. Italy pubmed.ncbi.nlm.nih.gov

Impact of luteinizing hormone suppression on hematopoietic recovery after intensive chemotherapy in patients with leukemia. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Luteinizing hormone-releasing hormone analogue: leuprorelin acetate for the prevention of menstrual bleeding in premenopausal women undergoing stem cell transplantation. [2013]

4. Italy pubmed.ncbi.nlm.nih.gov

Current use of androgens in bone marrow failure disorders: a report from the Severe Aplastic Anemia Working Party of the European Society of Blood and Marrow Transplantation. [2023]

5. Japan pubmed.ncbi.nlm.nih.gov

A randomized controlled study evaluating safety and efficacy of leuprorelin acetate every-3-months depot for 2 versus 3 or more years with tamoxifen for 5 years as adjuvant treatment in premenopausal patients with endocrine-responsive breast cancer. [2018]

6. France pubmed.ncbi.nlm.nih.gov

[Increased hematological toxicity of antineoplastic drugs with simultaneous androgenotherapy (author's transl)]. [2015]

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

Prevention of hypermenorrhea with leuprolide in premenopausal women undergoing bone marrow transplantation. [2019]

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

Luteinizing hormone-releasing hormone enhances T cell recovery following allogeneic bone marrow transplantation. [2021]