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Alkylating agents

Low-Dose Cyclophosphamide for Blood Cancers

Phase 1 & 2

Recruiting

Led By Christopher G Kanakry, M.D.

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have a histologically or cytologically confirmed hematologic malignancy with standard indication for allogeneic hematopoietic cell transplantation limited to one of the following: Acute myeloid leukemia (AML) of intermediate or adverse risk disease by the 2017 European LeukemiaNet criteria in first morphologic complete remission (<5% blasts in the bone marrow, no detectable abnormal peripheral blasts, and no extramedullary disease) AML of any risk in second or subsequent morphologic complete remission B-cell acute lymphoblastic leukemia in first or subsequent complete remission T-cell acute lymphoblastic leukemia with minimal residual disease detected after first line therapy and/or adverse genetics (no NOTCH1/FBXW7 mutation or presence of N/K-RAS mutation and/or PTEN gene alteration) Myelodysplastic syndrome of intermediate or higher score by the Revised International Prognostic Scoring System (IPSS-R) Primary myelofibrosis of intermediate-2 or higher risk by the DIPSS Chronic myelomonocytic leukemia Chronic myelogenous leukemia resistant to or intolerant of greater than or equal to 3 tyrosine kinase inhibitors or with history of accelerated phase or blast crisis B-cell lymphoma including Hodgkin lymphoma that has relapsed within 1 year of completion of primary treatment Chronic lymphocytic leukemia with 17p deletion and/or unmutated IgHV or refractory to or intolerant of both BTK and PI3K inhibitors Mature T or NK neoplasms as defined in the WHO guidelines of sufficient type and severity for allogeneic HCT based on the Prognostic Index for T-cell lymphoma (PIT) score of low-intermediate risk or higher or on recently published clinical practice guidelines Hematologic malignancy of dendritic cell or histiocytic cell type Multiple myeloma, stage III, relapsing after therapy with both a proteasome inhibitor and an immunomodulatory drug (IMiD) Age 15-65. Patients <18 years old must be at least 50 kg. Note: Because patients 15-17 years old and <50 kg are not able to be cared for on the adult oncology wards and by the investigative team, they are excluded. At least one potentially suitable HLA-haploidentical donor. Karnofsky performance score greater than or equal to 60 Adequate organ function defined as possessing all of the following: Cardiac ejection fraction greater than or equal to 45% by 2D ECHO; Forced expiratory volume-1 (FEV-1), forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO) (corrected for hemoglobin) all of greater than or equal to 50% predicted; Estimated serum creatinine clearance of greater than or equal to 60 ml/minute/1.73m(2) calculated using eGRF in the clinical lab for adults and the Schwartz formula for pediatric subjects; Total bilirubin less than or equal to 2X the upper limit of normal; Alanine aminotransferase and aspartate aminotransferase less than or equal to 3X the upper limit of normal.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 100 days

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a lower dose of the drug cyclophosphamide to see if it can help people with blood cancers have a more successful transplant with fewer side effects.

Who is the study for?

This trial is for people aged 15-65 with certain high-risk blood cancers like leukemia, lymphoma, or multiple myeloma that standard treatments can't cure. They must be in good health otherwise and have a relative who can donate stem cells. Pregnant women and those with severe illnesses or recent other cancer treatments are excluded.

What is being tested?

Researchers are testing if lower doses of the drug cyclophosphamide (PTCy) combined with shorter use of another immunosuppressant can make bone marrow transplants more successful for blood cancer patients while reducing side effects.

What are the potential side effects?

Potential side effects include reactions to chemotherapy such as nausea, fatigue, hair loss, increased risk of infections due to weakened immune system, and possible organ inflammation from the drugs used.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 100 days

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~100 days

This trial's timeline: 3 weeks for screening, Varies for treatment, and 100 days for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

aGVHD protection from PTCy 25 mg/kg

aGVHD protection from a reduced duration of MMF, in combination with PTCy 25 mg/kg/day

Secondary study objectives

Determine, at the PTCy dose or MMF duration used in phase II cohorts, the cumulative incidences

determine the shortest MMF duration without unacceptable acute GVHD to be used during phase II

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

6Treatment groups

Experimental Treatment

Active Control

Group I: Phase II efficacy of reduced duration MMFExperimental Treatment5 Interventions

MMF at duration identified from de-escalation evaluation.

Group II: Phase II EfficacyExperimental Treatment5 Interventions

PTCy at shortest duration, safe dose (from Phase I) to assess efficacy at providing adequate protection from grade 3-4 acute GVHD (up to 14 additional patients)

Group III: Phase I duration de-escalation of MMFExperimental Treatment5 Interventions

MMF at de-escalating duration (days +5 to +18 only, no MMF))

Group IV: Phase I Pilot for Comparative DataExperimental Treatment5 Interventions

Standard PTCy 50 mg/kg/day on days +3 and +4, in a small pilot (up to 5 evaluable patients) for comparative data

Group V: Phase I Dose De-escalationExperimental Treatment5 Interventions

PTCy at de-escalating doses (25 mg/kg/day on days +3 and +4, and PTCy 25 mg/kg on day +4) to assess for safety and determine Phase II dose (up to 12 evaluable patients)

Group VI: Donor ArmActive Control1 Intervention

Collection of bone marrow and/or PBSC (Up to 40 donors)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Mycophenolate Mofetil

1997

Completed Phase 4

~2380

Busulfan

2008